Modulators of proteins with phosphotyrosine recognition units

Abstract

Y—X—C(R′)═C(R″)COOR″′  (A 1 ) The present invention relates to novel protein tyrosine phosphatase modulating compounds having the general structure shown in Formula (A 1 ), to methods for their preparation, to compositions comprising the compounds, to their use for treatment of human and animal disorders, to their use for purification of proteins or glycoproteins, and to their use in diagnosis. The invention relates to modulation of the activity of molecules with phosphotyrosine recognition units, including protein tyrosine phosphatases (PTPases) and proteins with Src-homology-2 domains, in in vitro systems, microorganisms, eukaryoic cells, whole animals and human beings. R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, alkyl, arylalkyl. R″′ is selected from the group consisting of hydrogen, alkyl, substituted alkyl, aryl, arylalkyl. X is aryl. Y is selected from hydrogen or wherein (*) indicates a potential point of attachment to X.

What is claimed is:  
     
         1 . A protein tyrosine phosphatase activity-modulating compound with the structure depicted in Formula (B):  
       X—C(R′)═C(R″)COOR″′  (b)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 1 , —C 0-11 alkylCONR 2 R 3  wherein R 1 , R 2  and R 3  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 2  and R 3  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of 
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, —C 0-11 alkylCOOR 4 , —C 0-11 alkylCONR 5 R 6  wherein R 4 , R 5  and R 6  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 5  and R 6  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         2 . A compound as defined in  claim 1  wherein aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         3 . A compound as defined in  claim 1  wherein aryl is selected from thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, thiadiazolyl, or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         4 . A compound as defined in  claim 1  wherein aryl is selected from thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, phenothiazinyl, thiazolyl, isothiazolyl, benzthiazolyl, thiadiazolyl, or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         5 . A compound as defined in  claim 1  wherein aryl is selected from furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, phenoxazinyl, chromanyl, benzodioxolyl, hydroxypyronyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         6 . A compound as defined in  claim 1  wherein aryl is selected from pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, purinyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, thiadiazolyl, or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         7 . A compound as defined in  claim 1  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, benzothienyl, isobenzothienyl, furyl, benzofuranyl, isobenzofuranyl, pyrrolyl, indolyl, isoindolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, quinolyl, isoquinolyl, phthalazinyl, quinazolinyl, quinoxalinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, thiadiazolyl, or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         8 . A compound as defined in  claim 1  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, benzothienyl, furyl, benzofuranyl, pyrrolyl, indolyl, imidazolyl, benzimidazolyl, pyridyl, quinolyl, thiazolyl, benzthiazolyl, oxazolyl, benzoxazolyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         9 . A compound as defined in  claim 1  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         10 . A compound as defined in  claim 1  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         11 . A compound as defined in  claim 1  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         12 . A compound as defined in  claim 1  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         13 . A compound as defined in  claim 1  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         14 . A compound as defined in  claim 1  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         15 . A compound as defined in  claim 1  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         16 . A compound with the structure depicted in Formula (A2):  
       
         
           
           
               
               
           
         
       
       wherein at least one of R 1 , R 2  and R 3  substituents has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 4 , —C 0-11 alkylCONR 5 R 6  wherein R 4 , R 5  and R 6  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 5  and R 6  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of  
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, —C 0-11 alkylCOOR 7 , —C 0-11 alkylCONR 8 R 9  wherein R 7 , R 8  and R 9  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 8  and R 9  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, 
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein the remaining of R 1 , R 2  and R 3  are independently selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         17 . A compound as defined in  claim 16  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         18 . A compound as defined in  claim 16  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         19 . A compound as defined in  claim 16  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         20 . A compound as defined in  claim 16  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         21 . A compound as defined in  claim 16  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         22 . A compound as defined in  claim 16  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         23 . A compound as defined in  claim 16  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         24 . A compound with the structure depicted in Formula (A3):  
       
         
           
           
               
               
           
         
       
       wherein at least one of R 1 , R 2  and R 3  substituents has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 4 , —C 0-11 alkylCONR 5 R 6  wherein R 4 , R 5  and R 6  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 5  and R 6  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of 
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, arylC 1-11 alkylcarbonylamino, —C 0-11 alkylCOOR 7 , —C 0-11 alkylCONR 8 R 9  wherein R 7 , R 8  and R 9  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 8  and R 9  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein the remaining of R 1 , R 2  and R 3  are independently selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl, C 1-11 alkylcarbonyl, substituted C 1-11 alkylcarbonyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl, arylC 0-11 alkylcarbonyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl, mono-, di- and tri-substituted arylC 0 -C 11 alkylcarbonyl wherein the aryl substituents are defined as above,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         25 . A compound as defined in  claim 24  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         26 . A compound as defined in  claim 24  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         27 . A compound as defined in  claim 24  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         28 . A compound as defined in  claim 24  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         29 . A compound as defined in  claim 24  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         30 . A compound as defined in  claim 24  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         31 . A compound with the structure depicted in Formula (A4):  
       
         
           
           
               
               
           
         
       
       wherein at least one of R 1 , R 2  substituents has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-1 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 3 , —C 0-11 alkylCONR 4 R 5  wherein R 3 , R 4  and R 5  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 4  and R 5  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of 
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, —C 0-11 alkylCOOR 6 , —C 0-11 alkylCONR 7 R 8  wherein R 6 , R 7  and R 8  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 7  and R 8  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein the remaining of R 1 , R 2  is selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         32 . A compound as defined in  claim 31  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         33 . A compound as defined in  claim 31  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         34 . A compound as defined in  claim 31  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         35 . A compound as defined in  claim 31  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         36 . A compound as defined in  claim 31  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         37 . A compound as defined in  claim 31  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         38 . A compound as defined in  claim 31  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         39 . A compound with the structure depicted in Formula (A5):  
       
         
           
           
               
               
           
         
       
       wherein at least one of R 1 , R 2  substituents has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 3 , —C 0-11 alkylCONR 4 R 5  wherein R 3 , R 4  and R 5  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 4  and R 5  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of 
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 1-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, —C 0-11 alkylCOOR 6 , —C 0-11 alkylCONR 7 R wherein R 6 , R 7  and R 8  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 7  and R 8  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 (c) mono-, di- and ti-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein the remaining of R 1 , R 2  is selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         40 . A compound as defined in  claim 39  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         41 . A compound as defined in  claim 39  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         42 . A compound as defined in  claim 39  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         43 . A compound as defined in  claim 39  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         44 . A compound as defined in  claim 39  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         45 . A compound as defined in  claim 39  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         46 . A compound as defined in  claim 39  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         47 . A compound with the structure depicted in Formula (A6):  
       
         
           
           
               
               
           
         
       
       wherein at least one of R 1 , R 2 , R 3  and R 4  substituents has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 5 , —C 0-11 alkylCONR 6 R 7  wherein R 5 , R 6  and R 7  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 6  and R 7  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of  
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, —C 0-11 alkylCOOR 8 , —C 0-11 alkylCONR 9 R 10  wherein R 8 , R 9  and R 10  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 9  and R 10  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, 
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein the remaining of R 1 , R 2 , R 3  and R 4  are independently selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above, with the proviso that when R 3  and R 4  are selected from substituted phenyl or substituted furyl then the phenyl and furyl substituents exclude hydroxy, halo, trifluoromethyl, C 1-6 alkyl, C 1-6 alkyloxy, C 1-6 alkylthio, amino, C 1-6 alkylamino, di(C 1-6 alkyl)amino, phenylC 1-6 alkylamino and di(phenylC 1-6 alkyl)amino,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         48 . A compound as defined in  claim 47  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         49 . A compound as defined in  claim 47  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         50 . A compound as defined in  claim 47  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         51 . A compound as defined in  claim 47  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         52 . A compound as defined in  claim 47  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         53 . A compound as defined in  claim 47  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         54 . A compound as defined in  claim 47  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         55 . A compound with the structure depicted in Formula (A6):  
       
         
           
           
               
               
           
         
       
       wherein R 4  is selected from —COR 5 , —COOR 6 , —CONR 7 R 8  wherein R 5  thru R 8  are independently selected from hydrogen, C 1 -C 11 alkyl, substituted C 1-11 alkyl where the alkyl substituents are as defined below, optionally substituted arylC 0 -C 11 alkyl where the aryl substituents are as defined below, or R 7  and R 8  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, and wherein at least one of R 1 , R 2 , and R 3  substituents has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 11-1 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 9 , —C 0-11 alkylCONR 10 R 11  wherein R 9 , R 10  and R 11  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 10  and R 11  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of 
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, —C 0-11 alkylCOOR 12 , —C 0-11 alkylCONR 13 R 14  wherein R 12 , R 13  and R 14  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 13  and R 14  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein the remaining of R 1 , R 2  and R 3  are independently selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         56 . A compound as defined in  claim 55  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         57 . A compound as defined in  claim 55  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         58 . A compound as defined in  claim 55  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         59 . A compound as defined in  claim 55  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         60 . A compound as defined in  claim 55  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         61 . A compound as defined in  claim 55  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         62 . A compound as defined in  claim 55  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         63 . A compound with the structure depicted in Formula (A6):  
       
         
           
           
               
               
           
         
       
       wherein R 3  is selected from —COR 5 , —COOR 6 , —CONR 7 R 8  wherein R 5  thru R 8  are independently selected from hydrogen, C 1 -C 11 alkyl, substituted C 1-11 alkyl where the alkyl substituents are as defined below, optionally substituted arylC 0 -C 11 alkyl where the aryl substituents are as defined below, or R 7  and R 8  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, and wherein at least one of R 1 , R 2 , and R 4  substituents has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 1-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 9 , —C 0-11 alkylCONR 10 R 11  wherein R 9 , R 10  and R 11  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 10  and R 11  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of  
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, C 0-11 alkylCOOR 12 , —C 0-11 alkylCONR 13 R 14  wherein R 12 , R 13  and R 14  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 13  and R 14  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, 
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein the remaining of R 1 , R 2  and R 4  are independently selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         64 . A compound as defined in  claim 63  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         65 . A compound as defined in  claim 63  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         66 . A compound as defined in  claim 63  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         67 . A compound as defined in  claim 63  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         68 . A compound as defined in  claim 63  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         69 . A compound as defined in  claim 63  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         70 . A compound as defined in  claim 63  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         71 . A compound with the structure depicted in Formula (A7):  
       
         
           
           
               
               
           
         
       
       wherein R 2  is selected from —COR 5 , —COOR 6 , —CONR 7 R 8  wherein R 5  thru R 8  are independently selected from hydrogen, C 1 -C 11 alkyl, substituted C 1-11 alkyl where the alkyl substituents are as defined below, optionally substituted arylC 0 -C 11 alkyl where the aryl substituents are as defined below, or R 7  and R 8  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, and wherein at least one of R 1  and R 3  substituents has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 1-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 9 , —C 0-11 alkylCONR 10 R 11  wherein R 9 , R 10  and R 11  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 10  and R 11  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of 
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, C 0-11 alkylCOOR 12 , —C 0-11 alkylCONR 13 R 14  wherein R 12 , R 13  and R 14  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 13  and R 14  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein the remaining of R 1  and R 3  are independently selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         72 . A compound as defined in  claim 71  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         73 . A compound as defined in  claim 71  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         74 . A compound as defined in  claim 71  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         75 . A compound as defined in  claim 71  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         76 . A compound as defined in  claim 71  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         77 . A compound as defined in  claim 71  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         78 . A compound as defined in  claim 71  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         79 . A compound with the structure depicted in Formula (A8):  
       
         
           
           
               
               
           
         
       
       wherein at least one of R 1  and R 2  substituents has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 1-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 4 , —C 0-11 alkylCONR 5 R 6  wherein R 4 , R 5  and R 6  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 5  and R 6  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of  
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, —C 0-11 alkylCOOR 7 , C 0-11 alkylCONR 8 R 9  wherein R 7 , R 8  and R 9  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 8  and R 9  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, 
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein the remaining of R 1  and R 2  is independently selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above,  
 and wherein m is an integer between 0 and 4 and each R 3  is independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 1-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —CH═CHCOOR 10 ,  
 —CH═CHCONR 11 R 12 , —C 1-11 alkylCOOR 13 , —C 0-11 alkylCONR 14 R 15  wherein R 10  thru R 15  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 11  and R 12  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, or R 14  and R 15  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         80 . A compound as defined in  claim 79  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         81 . A compound as defined in  claim 79  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         82 . A compound as defined in  claim 79  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         83 . A compound as defined in  claim 79  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         84 . A compound as defined in  claim 79  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         85 . A compound as defined in  claim 79  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         86 . A compound as defined in  claim 79  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         87 . A compound with the structure depicted in Formula (A8):  
       
         
           
           
               
               
           
         
       
       wherein R 1  is selected from —COR 16 , —COOR 17 , —CONR 18 R 19  wherein R 16  thru R 19  are independently selected from hydrogen, C 1 -C 11 alkyl, substituted C 1-11 alkyl where the alkyl substituents are as defined below, optionally substituted arylC 0 -C 11 alkyl where the aryl substituents are as defined below, or R 18  and R 19  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, and wherein R 2  has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 1-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 4 , —C 0-11 alkylCONR 5 R 6  wherein R 4 , R 5  and R 6  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 5  and R 6  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of 
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, C 0-11 alkylCOOR 7 , —C 0-11 alkylCONR 8 R 9  wherein R 7 , R 8  and R 9  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 8  and R 9  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein R 2  is selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above,  
 and wherein m is an integer between 0 and 4 and each R 3  is independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 1-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, CH═CHCOOR 10 , CH═CHCONR 11 R 12 , C 0-11 alkylCOOR 13 , C 1-11 alkylCONR 14 R 15  wherein R 10  thru R 15  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 11  and R 12  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, or R 14  and R 15  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         88 . A compound as defined in  claim 87  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         89 . A compound as defined in  claim 87  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         90 . A compound as defined in  claim 87  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         91 . A compound as defined in  claim 87  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         92 . A compound as defined in  claim 87  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         93 . A compound as defined in  claim 87  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         94 . A compound as defined in  claim 87  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         95 . A compound with the structure depicted in Formula (A9):  
       
         
           
           
               
               
           
         
       
       wherein at least one of R 1  and R 2  substituents has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 0-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 4 , —C 0-11 alkylCONR 5 R 6  wherein R 4 , R 5  and R 6  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 5  and R 6  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of 
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, —C 0-11 alkylCOOR 7 , —C 0-11 alkylCONR 8 R 9  wherein R 7 , R 8  and R 9  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 8  and R 9  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein the remaining of R 1  and R 2  is independently selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above,  
 and wherein m is an integer between 0 and 3 and each R 3  is independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, C 0-11 alkyloxyC 1-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —CH═CHCOOR 10 , —CH═CHCONR 11 R 12 , —C 0-11 alkylCOOR 13 , C 0-11 alkylCONR 14 R 15  wherein R 10  thru R 15  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 11  and R 12  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, or R 14  and R 15  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         96 . A compound as defined in  claim 95  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         97 . A compound as defined in  claim 95  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         98 . A compound as defined in  claim 95  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         99 . A compound as defined in  claim 95  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         100 . A compound as defined in  claim 95  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         101 . A compound as defined in  claim 95  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         102 . A compound as defined in  claim 95  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         103 . A compound having the structure depicted in Formula (A9):  
       
         
           
           
               
               
           
         
       
       wherein R 1  or R 2  is selected from —COR 16 , —COOR 17 , —CONR 15 R 19  wherein R 16  thru R 19  are independently selected from hydrogen, C 1 -C 11 alkyl, substituted C 1-11 alkyl where the alkyl substituents are as defined below, optionally substituted arylC 0 -C 11 alkyl where the aryl substituents are as defined below, or R 18  and R 19  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, and wherein the remainder of R 1  or R 2  has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-1 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 4 , —C 0-11 alkylCONR 5 R 6  wherein R 4 , R 5  and R 6  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 5  and R 6  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of 
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, —C 0-11 alkylCOOR 7 , —C 0-11 alkylCONR 8 R 9  wherein R 7 , R 8  and R 9  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 8  and R 9  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein R 2  is selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above,  
 and wherein m is an integer between 0 and 3 and each R 3  is independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —CH═CHCOOR 10 ,  
 —CH═CHCONR 11 R 12 , —C 0-11 alkylCOOR 13, —C   0-11 alkylCONR 14 R 15  wherein R 10  thru R 15  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 11  and R 12  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent, or R 14  and R 15  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         104 . A compound as defined in  claim 103  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         105 . A compound as defined in  claim 103  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         106 . A compound as defined in  claim 103  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         107 . A compound as defined in  claim 103  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         108 . A compound as defined in  claim 103  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         109 . A compound as defined in  claim 103  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         110 . A compound as defined in  claim 103  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         111 . A compound with the structure depicted in Formula (A10):  
       
         
           
           
               
               
           
         
       
       wherein Z 1  and Z 2  are independently selected from the group consisting of OR 3 , SR 4 , NR 5 R 6 , wherein R 3 , R 4 , R 5 , R 6  are independently selected from: 
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl, C 1-11 alkylcarbonyl, substituted C 1-11 alkylcarbonyl wherein the alkyl substituents are defined as below,  
 (iii) arylC 0-11 alkyl, arylC 0-11 alkylcarbonyl;  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl; mono-, di- and tri-substituted arylC 0 -C 11 alkylcarbonyl wherein the aryl substituents are defined as in below,  
 and wherein at least one of R 1  and R 2  substituents has the general structure depicted in Formula (B)  
 X—C(R′)═C(R″)COOR″′  (B)  
 wherein  
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 0-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxy C 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 0-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 7 , —C 0-11 alkylCONR 8 R 9  wherein R 7 , R 8  and R 9  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 8  and R 9  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of 
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, —C 0-11 alkylCOOR 10 , —C 0-11 alkylCONR 11 R 12  wherein R 10 , R 11  and R 12  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 11  and R 12  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein the remaining of R 1 , and R 2  is independently selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         112 . A compound as defined in  claim 111  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         113 . A compound as defined in  claim 11   1  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         114 . A compound as defined in  claim 111  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         115 . A compound as defined in  claim 111  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         116 . A compound as defined in  claim 111  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         117 . A compound as defined in  claim 111  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         118 . A compound as defined in  claim 111  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         119 . A compound with the structure depicted in Formula (AI 1):  
       
         
           
           
               
               
           
         
       
       wherein at least one of R 1 , R 2  and R 3  substituents has the general structure depicted in Formula (B)  
       X—C(R′)═C(R″)COOR″′  (B)  
       wherein 
 (i) R′ and R″ are independently selected from the group consisting of hydrogen, halo, cyano, nitro, trihalomethyl, C 1-11 alkyl, optionally substituted arylC 1-11 alkyl wherein the aryl substituents are independently selected from the group consisting of hydrogen, halo, nitro, cyano, trihalomethyl, hydroxypyronyl, C 1-11 alkyl, arylC 1-11 alkyl, C 0-11 alkyloxyC 0-11 alkyl, arylC 0-11 alkyloxyC 0-11 alkyl, C 0-11 alkylthioC 0-11 alkyl, arylC 0-11 alkylthioC 0-11 alkyl, C 0-11 alkylaminoC 0-11 alkyl, arylC 1-11 alkylaminoC 0-11 alkyl, di(arylC 1-11 alkyl)aminoC 0-11 alkyl, C 1-11 alkylcarbonylC 0-11 alkyl, arylC 1-11 alkylcarbonylC 0-11 alkyl, C 1-11 alkylcarboxyC 0-11 alkyl, arylC 1-11 alkylcarboxyC 0-11 alkyl, C 1-11 alkylcarbonylaminoC 0-11 alkyl, arylC 1-11 alkylcarbonylaminoC 0-11 alkyl, —C 0-11 alkylCOOR 5 , C 0-11 alkylCONR 6 R 7  wherein R 5 , R 6  and R 7  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 6  and R 7  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent.  
 (ii) R″′ is selected from the group consisting of 
 (a) hydrogen,  
 (b) C 1-11 alkyl, substituted C 1-11 alkyl wherein the substituents are independently selected from halo, cyano, nitro, trihalomethyl, carbamoyl, tetrahydrofuryl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, hydroxypyronyl, C 0-11 alkyloxy, arylC 0-11 alkyloxy, C 0-11 alkylthio, arylC 0-11 alkylthio, C 0-11 alkylamino, arylC 0-11 alkylamino, di(arylC 0-11 alkyl)amino, C 1-11 alkylcarbonyl, arylC 1-11 alkylcarbonyl, C 1-11 alkylcarboxy, arylC 1-11 alkylcarboxy, C 1-11 alkylcarbonylamino, aryl C 1-11 alkylcarbonylamino, C 0-11 alkylCOOR 8 , C 0-11 alkylCONR 9 R 10  wherein R 8 , R 9  and R 10  are independently selected from hydrogen, C 1 -C 11 alkyl, arylC 0 -C 11 alkyl, or R 9  and R 10  are taken together with the nitrogen to which they are attached forming a cyclic system containing 3 to 8 carbon atoms with at least one C 1 -C 11 alkyl, arylC 0 -C 11 alkyl substituent,  
 (c) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above for R′ and R″,  
 
 (iii) X is a mono-, di- or trisubstituted aryl wherein the aryl substituents are defined as above for R′ and R″, and aryl is selected from phenyl, biphenyl, naphthyl, dihydronaphthyl, tetrahydronaphthyl, indenyl, indanyl, azulenyl, anthryl, phenanthryl, fluorenyl, pyrenyl, thienyl, benzothienyl, isobenzothienyl, 2,3-dihydrobenzothienyl, furyl, pyranyl, benzofuranyl, isobenzofuranyl, 2,3-dihydrobenzofuranyl, pyrrolyl, indolyl, isoindolyl, indolizinyl, indazolyl, imidazolyl, benzimidazolyl, pyridyl, pyrazinyl, pyradazinyl, pyrimidinyl, triazinyl, quinolyl, isoquinolyl, 4H-quinolizinyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 1,8-naphthyridinyl, pteridinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, chromanyl, benzodioxolyl, piperonyl, purinyl, hydroxypyronyl, pyrazolyl, triazolyl, tetrazolyl, thiazolyl, isothiazolyl, benzthiazolyl, oxazolyl, isoxazolyl, benzoxazolyl, oxadiazolyl, or thiadiazolyl,  
 and wherein the remaining of R 1 , R 2  and R 3  are independently selected from the group consisting of:  
 (i) hydrogen;  
 (ii) C 1-11 alkyl, substituted C 1-11 alkyl wherein the alkyl substituents are defined as above,  
 (iii) arylC 0-11 alkyl,  
 (iv) mono-, di- and tri-substituted arylC 0 -C 11 alkyl wherein the aryl substituents are defined as above,  
 or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
 
     
     
         120 . A compound as defined in  claim 119  wherein aryl is selected from phenyl, naphthyl, biphenyl, thienyl, furyl, pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         121 . A compound as defined in  claim 119  wherein aryl is phenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         122 . A compound as defined in  claim 119  wherein aryl is naphthyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         123 . A compound as defined in  claim 119  wherein aryl is biphenyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         124 . A compound as defined in  claim 119  wherein aryl is thienyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         125 . A compound as defined in  claim 119  wherein aryl is furyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         126 . A compound as defined in  claim 119  wherein aryl is pyridyl,  
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         127 . A compound as defined in  claim 1  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         128 . A compound as defined in  claim 1  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         129 . A compound as defined in  claim 63  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         130 . A compound as defined in  claim 63  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         131 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         132 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         133 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         134 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         135 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         136 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         137 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         138 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         139 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         140 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         141 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         142 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         143 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         144 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         145 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         146 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         147 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         148 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         149 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         150 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         151 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         152 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         153 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         154 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         155 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         156 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         157 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         158 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         159 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         160 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         161 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         162 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         163 . A compound with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         164 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         165 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         166 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         167 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         168 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         169 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         170 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         171 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         172 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         173 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         174 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         175 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         176 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         177 . A compound with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         178 . A compound as defined in  claim 39  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         179 . A compound as defined in  claim 39  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         180 . A compound as defined in  claim 39  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         181 . A compound as defined in  claim 3   9  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         182 . A compound as defined in  claim 39  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         183 . A compound as defined in  claim 39  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         184 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         185 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         186 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         187 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         189 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         190 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         191 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         192 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         193 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         194 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         195 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         196 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         197 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         198 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         199 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         200 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         201 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         202 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         203 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         204 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         205 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         206 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         207 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         208 . A compound as defined in  claim 47  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         209 . A compound as defined in  claim 63  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         210 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         211 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         212 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         213 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         214 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         215 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         216 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         217 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         218 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         219 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         220 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         221 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         222 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         223 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         224 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         225 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         226 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         227 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         228 . A compound as defined in  claim 24  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         229 . A compound as defined in  claim 55  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         230 . A compound as defined in  claim 71  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         231 . A compound as defined in  claim 79  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         232 . A compound as defined in  claim 79  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         233 . A compound as defined in  claim 79  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         234 . A compound as defined in  claim 79  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         235 . A compound as defined in  claim 79  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         236 . A compound as defined in  claim 79  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         237 . A compound as defined in  claim 87  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         238 . A compound as defined in  claim 87  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         239 . A compound as defined in  claim 95  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         240 . A compound as defined in  claim 103  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         241 . A compound as defined in  claim 103  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         242 . A compound as defined in  claim 111  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         243 . A compound as defined in  claim 111  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         244 . A compound as defined in  claim 1  I with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         245 . A compound as defined in  claim 111  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         246 . A compound as defined in  claim 111  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         247 . A compound as defined in  claim 119  with the structure as depicted below  
       
         
           
           
               
               
           
         
       
       or its pharmaceutically acceptable salts, prodrugs, esters, or solvates thereof.  
     
     
         248 . A pharmaceutical composition comprising as active component a compound according to any one of the preceding compound claims together with a pharmaceutically acceptable carrier or diluent.  
     
     
         249 . A pharmaceutical composition suitable for modulating the activity of PTPases or other molecules with tyrosine phosphate recognition unit(s) comprising an effective amount of a compound according to any one of the preceding compound claims together with a pharmaceutically acceptable carrier or diluent.  
     
     
         250 . The pharmaceutical composition according to any one of the claims  248  or  249  suitable for treating or preventing type I diabetes, type II diabetes, impaired glucose tolerance, insuline resistance, obesity, immune dysfunctions including autoimmunity and AIDS, diseases with dysfunctions of the coagulation system, allergic diseases, osteoperosis, proliferative disorders including cancer and psoriosis, diseases with decreased or increased synthesis or effects of growth hormone, diseases with decreased or increased synthesis of hormones or cytokines that regulate the release of/or response to growth hormone, diseases of the brain including Alzheimer's disease and schizophrnia, and infectious diseases.  
     
     
         251 . The pharmaceutical composition according to any one of the claims  248 ,  249  or  250  comprising between 0.5 mg and 1000 mg of a compound according to any one of the preceding compound claims per unit dose.  
     
     
         252 . A method of modulating the activity of PTPases or other molecules with phosphotyrosine recognition unit(s) in a subject in need of such treatment comprising administering to said subject an effective amount of a compound or composition according to any one of the preceding compound or composition claims.  
     
     
         253 . The use of a compound according to any one of the preceding compound claims for preparing a medicament.  
     
     
         254 . The use of a compound according to any one of the preceding compound claims for preparing a medicament for modulating the activity of PTPases or other molecules with phosphotyrosine recognition unit(s).  
     
     
         255 . The use of a compound according to any one of the preceding compound claims for preparing a medicament for treating or preventing type I diabetes, type II diabetes, impaired glucose tolerance, insuline resistance, obesity, immune dysfunctions including autoimmunity and AIDS, diseases with dysfunctions of the coagulation system, allergic diseases, osteoperosis, proliferative disorders including cancer and psoriasis, diseases with decreased or increased synthesis or effects of growth hormone, diseases with decreased or increased synthesis of hormones or cytokines that regulate the release of/or response to growth hormone, diseases of the brain including Alzheimer's disease and schizophrnia, and infectious diseases.  
     
     
         256 . The use of a compound according to any one of the preceding compound claims for preparing a medicament for treating a subject in need of such treatment.  
     
     
         257 . The use of a compound according to any one of the preceding compound claims for preparing a medicament for use as an immunosuppressant.  
     
     
         258 . An immobilized compound comprising a suitable solid-phase coupled with a compound according to any one of the preceding compound claim.  
     
     
         259 . A method for coupling a compound according to any one of the preceding compound claims to a suitable solid-phase matrix.  
     
     
         260 . A method for isolating a protein or a glycoprotein with affinity for a compound according to any one of the preceding compound claims from a biological sample, comprising 
 (1) contacting an immobilized compound according to  claim 258  with said biological sample in order for said immobilized compound to form a complex by binding said protein or glycoprotein    (2) removing unbound material from said biological sample and isolating said complex    (3) extracting said protein or glycoprotein from said complex.    
     
     
         261 . A method for isolating a protein-tyrosine phosphatase with affinity for a compound according to any one of the preceding compound claims from a biological sample, comprising 
 (1) contacting an immobilized compound according to  claim 258  with said biological sample in order for said immobilized compound to form a complex by binding said protein-tyrosine phosphatase    (2) removing unbound material from said biological sample and isolating said complex    (3) extracting said protein-tyrosine phosphatase from said complex.    
     
     
         262 . A method for isolating a Src-homology 2 domain containing protein or a phosphotyrosine binding domain containg protein with affinity for a compound according to any one of the preceding compound claims from a biological sample, comprising 
 (1) contacting an immobilized compound according to  claim 258  with said biological sample in order for said immobilized compound to form a complex by binding said Src-homology 2 domain containing protein or a phosphotyrosine binding domain containg protein    (2) removing unbound material from said biological sample and isolating said complex    (3) extracting said Src-homology 2 domain containing protein or a phosphotyrosine binding domain containg protein from said complex.    
     
     
         263 . A compound according to any one of the preceding compound claims coupled to a fluorescent or radioactive molecule.  
     
     
         264 . A method for coupling a fluorescent or radioactive molecule to a compound according to any one of the preceding compound claims comprising 
 (1) contacting said compound with said fluorescent or radioactive molecule in a reaction mixture to produce a complex    (2) removing uncomplexed material and isolating said complex from said reaction mixture.    
     
     
         265 . A method for detecting a protein-tyrosine phosphatase or other molecules with phosphotyrosine recognition unit(s) in a cell or in a subject using a compound according to  claim 263  comprising 
 (1) contacting said cell or an extract thereof or a biological sample from said subject or by injecting said compound into said subject in order for said compound to produce a complex with said protein-tyrosine phosphatase or said other molecules with phosphotyrosine recognition unit(s)  
 (2) detecting said complex, thereby detecting the presence of said protein-tyrosine phosphatase or said other molecules with phosphotyrosine recognition unit(s).  
 
     
     
         266 . A method for quantifying the amount of protein-tyrosine phosphatase or other molecules with phosphotyrosine recognition unit(s) in a cell or in a subject using a compound according to  claim 263  comprising 
 (1) contacting said cell or an extract thereof or a biological sample from said subject or by injecting said compound into said subject in order for said compound to produce a complex with said protein-tyrosine phosphatase or said other molecules with phosphotyrosine recognition unit(s)  
 (2) measuring the amount of said complex, thereby detecting the presence of said protein-tyrosine phosphatase or said other molecules with phosphotyrosine recognition unit(s).  
 
     
     
         267 . A method for determining the function of a given protein-tyrosine phosphatase or group of protein-tyrosine phosphatases or said molecules with phosphotyrosine recognition unit(s) in a cell or in a subject using a compound according to  claim 263  comprising 
 (1) contacting said cell or an extract thereof or a biological sample from said subject or by injecting said compound into said subject in order for said compound to produce a complex with said protein-tyrosine phosphatase or said other molecules with phosphotyrosine recognition unit(s)  
 (2) measuring the biological effects induced by said complex.