US2008075692A1PendingUtilityA1

Methods for treating blood disorders

Assignee: PERRINE SUSAN PPriority: May 9, 2006Filed: May 9, 2007Published: Mar 27, 2008
Est. expiryMay 9, 2026(expired)· nominal 20-yr term from priority
C07D 311/12C07D 285/125A61K 31/517A61K 31/353A61K 31/194A61P 7/06A61P 7/00A61K 31/433A61P 43/00A61K 31/415A61K 31/39A61K 31/36A61K 31/192
59
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Claims

Abstract

Methods of treating blood disorders are described.

Claims

exact text as granted — not AI-modified
1 . A method for treating or preventing a blood disorder in a subject, comprising administering to said subject an effective amount of a compound of formula I:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is hydroxy or alkoxy;  
 X is C(O), C(S), SO, SO 2  or PO 2 ;  
 R 2  and R 3  are each independently hydrogen, alkyl, halogen, hydroxyl, thiol, alkenyl, alkynyl, aryl, acyl, alkoxy, amino, alkylamino or heterocyclic;  
 R 4  is alkyl, cycloalkyl, alkenyl, alkynyl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, heteroaryl, halogen or  
                     
 R 5  is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy, nitro, halogen or optionally linked to R 6  to form a ring;  
 R 6  is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy, nitro, halogen or optionally linked to R 5  or R 7  to form a ring;  
 R 7  is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy, nitro, halogen or optionally linked to R 6  or R 8  to form a ring;  
 R 8  is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy, nitro, halogen or optionally linked to R 7  or R 9  to form a ring;  
 R 9  is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy, nitro, halogen or optionally linked to R 8  to form a ring;  
 and racemates, isolated enantiomers or diastereomers, and pharmaceutically acceptable salts thereof;  
 provided that when R 4  is  
                     
  R 5 , R 6 , R 7 , R 8 , and R 9  are each not hydrogen; and when R 6 , R 7 , R 8 , and R 9  are each hydrogen, R 5  is not methoxy; and when R 5 , R 7 , R 8 , R 9  are hydrogen, R 6  is not methoxy; and when R 5 , R 8  and R 9  are hydrogen, R 6  and R 7  are not methoxy.  
 
     
     
         2 . The method of  claim 1 , wherein R 1  is hydroxy, X is C(O), R 4  is  
       
         
           
           
               
               
           
         
       
       and R 2 , R 3  and R 5  are each hydrogen.  
     
     
         3 . The method of  claim 2 , wherein R 6 , R 8  and R 9  are each hydrogen, and R 7  is alkoxy.  
     
     
         4 . The method of  claim 3 , wherein R 7  is methoxy.  
     
     
         5 . The method of  claim 2 , wherein R 7  and R 8  are each hydrogen, and R 6  and R 9  are each alkyl.  
     
     
         6 . The method of  claim 5 , wherein R 6  and R 9  are methyl.  
     
     
         7 . The method of  claim 2 , wherein R 8  are R 9  are each hydrogen and R 6  and R 7  are each hydroxyl.  
     
     
         8 . The method of  claim 2 , wherein R 8  are R 9  are each hydrogen and R 6  and R 7  are linked by —O—CH 2 —O— to form a ring.  
     
     
         9 . The method of  claim 2 , wherein R 6  and R 9  are each hydrogen, R 7  is alkoxy and R 8  is hydroxyl.  
     
     
         10 . The method of  claim 1 , wherein R 4  is heteroaryl.  
     
     
         11 . The method of  claim 10 , wherein R 4  is quinoline or substituted or unsubstituted thiophene.  
     
     
         12 . The method of  claim 11 , wherein R 4  is chlorothiophene.  
     
     
         13 . The method of  claim 1 , wherein said compound is:  
       
         
           
           
               
               
           
         
       
     
     
         14 . A method for treating or preventing a blood disorder in a subject, comprising administering to said subject an effective amount of a compound of formula II:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1′  is hydroxy or alkoxy;  
 Y is C(O);  
 n is 0 or an integer from 1 to 5;  
 R 10  and R 10′  are each independently hydrogen, alkyl, halogen, hydroxyl, thiol, alkenyl, alkynyl, aryl, acyl, alkoxy, amino, alkylamino, heterocyclic or optionally joined to form a ring;  
 R 11  is CR 11′ R 11″ R 11′″ , alkenyl, cycloalkyl, alkynyl, arylalkyl, amido, alkylamino, amino, arylamino, carbonylalkyl, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, heteroaryl, hydroxy, halogen or  
                     
 R 11′  and R 11″  are each independently hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxyl, halogen or R 11′  and R 11″  are optionally joined to form a ring;  
 R 11′″  is alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy or halogen;  
 R 12  is hydrogen, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic or optionally linked to R 13  to form a ring;  
 R 13  is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy or optionally linked to R 12  or R 14  to form a ring;  
 R 14  is hydrogen, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, halogen or optionally linked to R 13  or R 15  to form a ring;  
 R 15  is hydrogen, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, halogen or optionally linked to R 14  or R 16  to form a ring;  
 R 16  is hydrogen, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, halogen or optionally linked to R 15  to form a ring;  
 and racemates, isolated enantiomers or diastereomers, and pharmaceutically acceptable salts thereof;  
 provided that when R 11  is  
                     
  R 12 , R 13 , R 14 , R 15 , and R 16  are each not hydrogen; and provided when n is 2, R 11  is  
                     
  and R 10 , R 10′ , R 12 , R 15 , and R 16  are hydrogen, then R 14  and R 15  are not methoxy; and provided when n is 1, R 11  is  
                     
  and R 10 , R 10′ , R 13 , R 14 , and R 16  are hydrogen, then R 12  and R 15  are not methoxy.  
 
     
     
         15 . The method of  claim 14 , wherein R 1′  is hydroxy.  
     
     
         16 . The method of  claim 15 , wherein n is 5, R 10  and R 10′  are hydrogen and R 11  is alkylcarbonyl.  
     
     
         17 . The method of  claim 15 , wherein n is 2, R 10  and R 10′  are each hydrogen and R 11  is CR 11′ R 11″ R 11′″ .  
     
     
         18 . The method of  claim 17 , wherein R 11′  and R 11″  are joined by —(CH 2 ) 5 — to form a cyclohexyl ring and R 11′″  is a substituted or unsubstituted heterocycle.  
     
     
         19 . The method of  claim 18 , wherein R 11′″  is chlorothiophene.  
     
     
         20 . The method of  claim 15 , wherein n is 0.  
     
     
         21 . The method of  claim 20 , wherein R 11  is  
       
         
           
           
               
               
           
         
       
     
     
         22 . The method of  claim 21 , wherein R 13 , R 14 , R 15 , and R 16  are hydrogen.  
     
     
         23 . The method of  claim 22 , wherein R 12  is arylthioalkyl.  
     
     
         24 . The method of  claim 22 , wherein R 12  is alkoxy substituted aryloxy.  
     
     
         25 . The method of  claim 21 , wherein R 12 , R 14 , R 15  and R 16  are hydrogen.  
     
     
         26 . The method of  claim 25 , wherein R 13  is a substituted or unsubstituted heterocycle.  
     
     
         27 . The method of  claim 26 , wherein R 13  is chromen-2-one, nitro-substituted pyrazole, or chloro-substituted pyrazole.  
     
     
         28 . The method of  claim 21 , wherein R 12 , R 13 , R 15  and R 16  are hydrogen and R 13  is alkoxy.  
     
     
         29 . The method of  claim 28 , wherein R 13  is ethoxy.  
     
     
         30 . The method of  claim 21 , wherein R 12 , R 15  and R 16  are hydrogen, and R 13  and R 14  are linked by —N(H)C(O)CH 2 S— to form a ring.  
     
     
         31 . The method of  claim 21 , wherein R 14 , R 15  and R 16  are each hydrogen, and R 12  and R 13  are linked by —CH═C(CH 3 )O— to form a ring.  
     
     
         32 . The method of  claim 20 , wherein R 11  is a substituted or unsubstituted heterocycle.  
     
     
         33 . The method of  claim 32 , wherein R 11  is a substituted aryl-substituted furan.  
     
     
         34 . The method of  claim 20 , wherein R 11  is a substituted or unsubstituted cycloalkyl.  
     
     
         35 . The method of  claim 34 , wherein R 11  is tetrahydrobenzothiadiazole or dihydrobenzothiophenone.  
     
     
         36 . The method of  claim 15 , wherein n is 1.  
     
     
         37 . The method of  claim 36 , wherein R 10  and R 10′  are hydrogen.  
     
     
         38 . The method of  claim 37 , wherein R 11  is a substituted or unsubstituted cycloalkyl.  
     
     
         39 . The method of  claim 38 , wherein R 11  is dimethylcyclobutane carboxylic acid.  
     
     
         40 . The method of  claim 37 , wherein R 11  is  
       
         
           
           
               
               
           
         
       
     
     
         41 . The method of  claim 40 , wherein R 12 , R 13  and R 16  are hydrogen, and R 14  and R 15  are linked by —O—CH 2 —O— to form a ring.  
     
     
         42 . The method of  claim 37 , wherein R 11  is a substituted or unsubstituted heterocycle.  
     
     
         43 . The method of  claim 42 , wherein R 11  is substituted thiazolidinedione, substituted pyridinone or substituted pyrazole.  
     
     
         44 . The method of  claim 37 , wherein R 11  is substituted or unsubstituted arylamino.  
     
     
         45 . The method of  claim 44 , wherein R 11  arylamino is trifluorothio-substituted arylamino.  
     
     
         46 . The method of  claim 37 , wherein R 11  is substituted or unsubstituted arylthio or substituted or unsubstituted heterocyclic thio.  
     
     
         47 . The method of  claim 46 , wherein R 11  is methoxyphenylthio.  
     
     
         48 . The method of  claim 46 , said R 11  is substituted triazolethio, substituted thiadiazolethio or substituted thiophenethio.  
     
     
         49 . The method of  claim 37 , wherein R 11  is CR 11′ R 11″ R 11′″ .  
     
     
         50 . The method of  claim 49 , wherein R 11′  is hydrogen, R 11″  is amino and R 11′″  is alkoxy-substituted aryl.  
     
     
         51 . The method of  claim 36 , wherein R 10  is hydrogen and R 10′  is alkyl.  
     
     
         52 . The method of  claim 51 , wherein R 10′  is isopropyl.  
     
     
         53 . The method of  claim 52 , wherein R 11  is substituted or unsubstituted arylthio.  
     
     
         54 . The method of  claim 53 , wherein R 11  is alkoxy-substituted phenylthio or alkoxy-substituted pyrimadinylthio.  
     
     
         55 . The method of  claim 51 , wherein R 10′  is ethyl.  
     
     
         56 . The method of  claim 55 , wherein R 11  is heteroarylamino.  
     
     
         57 . The method of  claim 56 , wherein R 11  is quinazolinylamino.  
     
     
         58 . The method of  claim 36 , wherein R 10  and R 10′  are linked by —(CH 2 ) 5 — to form a cyclohexyl ring.  
     
     
         59 . The method of  claim 58 , wherein R 11  is heterocyclic substituted carbonylalkyl.  
     
     
         60 . The method of  claim 14 , wherein said compound is  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         61 . A method for treating or preventing a blood disorder in a subject, comprising administering to said subject an effective amount of a compound of formula III:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1″  is hydroxy or alkoxy;  
 Z is C(S), SO, SO 2  or PO 2 ;  
 m is 0 or an integer from 1-5;  
 R 17  and R 17′  are each independently hydrogen, alkyl, halogen, hydroxyl, thiol, alkenyl, alkynyl, aryl, acyl, alkoxy, amino, alkylamino or heterocyclic;  
 R 18  is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, heteroaryl, hydroxyl or halogen;  
 and racemates, isolated enantiomers or diastereomers, and pharmaceutically acceptable salts thereof.  
 
     
     
         62 . The method of  claim 61 , wherein R 1″  is hydroxyl, Z is SO 2 , m is 0, and R 18  is disubstituted aryl.  
     
     
         63 . The method of  claim 62 , wherein R 18  is substituted by nitro and fluoro.  
     
     
         64 . The method of  claim 61 , wherein the compound is of the formula:  
       
         
           
           
               
               
           
         
       
     
     
         65 . A method for treating or preventing a blood disorder in a subject, comprising administering to said subject an effective amount of a compound of formula:  
       
         
           
           
               
               
           
         
       
     
     
         66 . The method of any one of claims  1 ,  14 ,  61  or  65 , wherein the blood disorder is sickle cell anemia, β-thalassemia, neutropenia or thrombocytopenia.  
     
     
         67 . The method of any one of claims  1 ,  14 ,  61  or  65 , wherein said compound stimulates fetal hemoglobin production.  
     
     
         68 . The method of any one of  claim 1 ,  14 ,  61  or  65 , wherein said compound stimulates hematopoiesis.  
     
     
         69 . The method of any one of claims  1 ,  14 ,  61  or  65 , wherein said compound stimulates erythropoiesis.  
     
     
         70 . The method of any one of claims  1 ,  14 ,  61  or  65 , wherein said compound stimulates myelopoiesis.  
     
     
         71 . The method of any one of claims  1 ,  14 ,  61  or  65 , wherein said compound stimulates neutrophil production.  
     
     
         72 . The method of any one of claims  1 ,  14 ,  61  or  65 , wherein said compound is administered in combination with one or more cytokines.  
     
     
         73 . The method of  claim 72 , wherein said cytokine is selected from the group consisting of IL-3, GM-CSF, C-CSF, SCF and IL-6.  
     
     
         74 . A pharmaceutical composition comprising an effective amount of a compound of any one of claims  1 ,  13 ,  14 ,  60 ,  61  or  65  and racemates, isolated enantiomers or diastereomers thereof, and a pharmaceutically acceptable carrier.  
     
     
         75 . A compound of formula I:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1  is hydroxy or alkoxy;  
 X is C(O), C(S), SO, SO 2  or PO 2 ;  
 R 2  and R 3  are each independently hydrogen, alkyl, halogen, hydroxyl, thiol, alkenyl, alkynyl, aryl, acyl, alkoxy, amino, alkylamino or heterocyclic;  
 R 4  is alkyl, cycloalkyl, alkenyl, alkynyl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, heteroaryl, halogen or  
                     
 R 5  is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy, nitro, halogen or optionally linked to R 6  to form a ring;  
 R 6  is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy, nitro, halogen or optionally linked to R 5  or R 7  to form a ring;  
 R 7  is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy, nitro, halogen or optionally linked to R 6  or R 8  to form a ring;  
 R 8  is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy, nitro, halogen or optionally linked to R 7  or R 9  to form a ring;  
 R 9  is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy, nitro, halogen or optionally linked to R 8  to form a ring;  
 and racemates, isolated enantiomers or diastereomers, and pharmaceutically acceptable salts thereof;  
 provided that when R 4  is  
                     
  R 5 , R 6 , R 7 , R 8 , and R 9  are each not hydrogen; and when R 6 , R 7 , R 8 , and R 9  are each hydrogen, R 5  is not methoxy; and when R 5 , R 7 , R 8 , R 9  are hydrogen, R 6  is not methoxy; and when R 5 , R 8  and R 9  are hydrogen, R 6  and R 7  are not methoxy;  
 and provided that the compound is not a compound of  claim 13 .  
 
     
     
         76 . A compound of formula II:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1′  is hydroxy or alkoxy;  
 Y is C(O);  
 n is 0 or an integer from 1 to 5;  
 R 10  and R 10′  are each independently hydrogen, alkyl, halogen, hydroxyl, thiol, alkenyl, alkynyl, aryl, acyl, alkoxy, amino, alkylamino, heterocyclic or optionally joined to form a ring;  
 R 11  is CR 11′ R 11″ R 11′″ , alkenyl, cycloalkyl, alkynyl, arylalkyl, amido, alkylamino, amino, arylamino, carbonylalkyl, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, heteroaryl, hydroxy, halogen or  
                     
 R 11′  and R 11″  are each independently hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxyl, halogen or R 11′  and R 11″  are optionally joined to form a ring;  
 R 11′″  is alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy or halogen;  
 R 12  is hydrogen, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic or optionally linked to R 13  to form a ring;  
 R 13  is hydrogen, alkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, hydroxy or optionally linked to R 12  or R 14  to form a ring;  
 R 14  is hydrogen, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, halogen or optionally linked to R 13  or R 15  to form a ring;  
 R 15  is hydrogen, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, halogen or optionally linked to R 14  or R 16  to form a ring;  
 R 16  is hydrogen, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, halogen or optionally linked to R 15  to form a ring;  
 and racemates, isolated enantiomers or diastereomers, and pharmaceutically acceptable salts thereof;  
 provided that when R 11  is  
                     
  R 12 , R 13 , R 14 , R 15 , and R 16  are each not hydrogen; and provided when n is 2, R 11  is  
                     
  and R 10 , R 10′ , R 12 , R 15 , and R 16  are hydrogen, then R 14  and R 15  are not methoxy; and provided when n is 1, R 11  is  
                     
 and R 10 , R 10′ , R 13 , R 14 , and R 16  are hydrogen, then R 12  and R 15  are not methoxy;  
 and provided that the compound is not a compound of  claim 60 .  
 
     
     
         77 . A compound of formula III:  
       
         
           
           
               
               
           
         
       
       wherein 
 R 1″  is hydroxy or alkoxy;  
 Z is C(S), SO, SO 2  or PO 2 ;  
 m is 0 or an integer from 1-5;  
 R 17  and R 17′  are each independently hydrogen, alkyl, halogen, hydroxyl, thiol, alkenyl, alkynyl, aryl, acyl, alkoxy, amino, alkylamino or heterocyclic;  
 R 18  is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, arylalkyl, amido, alkylamino, amino, arylamino, alkylcarbonyl, arylcarbonyl, alkylaminocarbonyl, alkoxy, alkoxycarbonyl, alkylcarbonyloxy, alkyloxycarbonyloxy, arylcarbonyloxy, aryloxy, thiol, alkylthio, arylthio, alkenyl, heterocyclic, heteroaryl, hydroxyl or halogen;  
 and racemates, isolated enantiomers or diastereomers, and pharmaceutically acceptable salts thereof;  
 provided that the compound is not a compound of  claim 64.

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