Novel 3,5-disubstituted-3h-imidazo[4,5-b]pyridine and 3,5- disubstituted -3h-[1,2,3]triazolo[4,5-b] pyridine compounds as modulators of c-met protein kinases

Abstract

The present invention provides compounds useful as c-Met protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of c-Met kinase mediated disease or disorders with them.

1 - 45 . (canceled) 
     
     
         46 . A method for the treatment of a c-Met associated disease or disorder, comprising the step of administering to a subject in need thereof an effective amount of a compound of formula (IA-I) 
       
         
           
           
               
               
           
         
       
       or a tautomer, stereoisomer, enantiomer, diastereomer, pharmaceutically acceptable salt, or N-oxide thereof, wherein
 X is CR 1  or N; 
 D is monocyclic aryl, wherein D is substituted with a group E which is selected from —CONH—O—(CR x R y ) p —OR x , and —CONH—O—(CR x R y ) p -[cycloalkyl]-(CR x R y ) p —OR x ; and further D can optionally be substituted with one or more of R z ; 
 L 2  is —(CR a R b )—; 
 Cy 2  is substituted or unsubstituted heteroaryl; 
 each occurrence of R 1  and R 2  may be same or different and is independently selected from hydrogen, nitro, hydroxy, cyano, halogen, —OR a , —S(═O) q —R a , —NR a R b , —C(═Y)—R a , —CR a R b —C(═Y)—R a , —CR a R b —Y—CR a R b R b , —C(═Y)—NR a R b , —NR a R b —C(═Y)—NR a R b , —S(═O) q —NR a R b —, —NR a R b —S(═O) q —NR a R b , —NR a R b —NR a R b , substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted C 3-6  cycloalkyl, substituted or unsubstituted C 3-6  cycloalkylalkyl, and substituted or unsubstituted C 3-6  cycloalkenyl; 
 each occurrence of Y is independently selected from O, S, and NR a ; 
 each occurrence of R a  and R b  may be same or different and are independently selected from hydrogen, nitro, hydroxy, cyano, halogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted C 3-6  cycloalkyl, substituted or unsubstituted C 3-6  cycloalkylalkyl, and substituted or unsubstituted C 3-6  cycloalkenyl, or when two R a  and/or R b  substituents are directly bound to a common atom, they may be joined to form a substituted or unsubstituted, saturated or unsaturated 3-10 member ring, which may optionally include one or more heteroatoms which may be same or different and are selected from O, NR c  or S; 
 each occurrence of R c  is independently selected from hydrogen, nitro, hydroxy, cyano, halogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted C 3-6  cycloalkyl, substituted or unsubstituted C 3-6  cycloalkylalkyl, and substituted or unsubstituted C 3-6  cycloalkenyl; 
 each occurrence of R x  and R y  is independently selected from hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, oxo (═O), thio (═S), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted heterocycyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, —COOR z , —C(O)R z , —C(S)R z , —C(O)NR z R z , —C(O)ONR z R z , —NR z R z , —NR z CONR z R z , —N(R z )SOR z , —N(R z )SO 2 R z , —(═N—N(R z )R z ), —NR z C(O)OR z , —NR z C(O)R z —, —NR x C(S)R y —NR z C(S)NR z R z , —SONR z R z —, —SO 2 NR z R z —, —OR z , —OR z C(O)NR z R z , —OR z C(O)OR z —, —OC(O)R z , —OC(O)NR z R z , —R z NR z C(O)R z , —R z OR z , —R z C(O)OR z , —R z C(O)NR z R z , —R z C(O)R z , —R z OC(O)R z , —SR z , —SOR z , —SO 2 R z , and —ONO 2 , or any two of R x  and R y  which are directly bound to a common atom may be joined to form (i) a substituted or unsubstituted, saturated or unsaturated 3-14 membered ring, which may optionally include one or more heteroatoms which may be the same or different and are selected from O, NR z  or S, or (ii) an oxo (═O), thio (═S) or imino (═NR z ); wherein 
 each occurrence of R z  is independently hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, oxo (═O), thio (═S), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted heterocycyl, substituted or unsubstituted heterocyclcyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, and —ONO 2 , or any two of R z  which are directly bound to a common atom may be joined to form (i) a substituted or unsubstituted, saturated or unsaturated 3-14 membered ring, which may optionally include one or more heteroatoms which may be the same or different and are selected from O, NR′ (where R′ is H or alkyl) or S, or (ii) an oxo (═O), thio (═S) or imino (═NR z ); 
 each occurrence of p independently represents 1, 2, 3, 4, 5, 6, 7 or 8; and 
 each occurrence of q independently represents 0, 1 or 2. 
 
     
     
         47 . The method of  claim 46 , wherein the c-Met associated disease, disorder or condition is an immune system-related disease, a disease or disorder involving inflammation, cancer or other proliferative disease, a hepatic disease or disorder, or a renal disease or disorder. 
     
     
         48 . The method of  claim 46 , wherein
 D is   
       
         
           
           
               
               
           
         
       
       and
 X 1 , X 2  and X 3  are independently selected from —CR z  and —CR z ═CR z . 
 
     
     
         49 . The method of  claim 46 , wherein
 L 2 -Cy 2  is   
       
         
           
           
               
               
           
         
       
       (where the squiggly line represents the bond to the bicyclic core in formula (IA-I));
 each occurrence of R a  and R b  are independently selected from hydrogen, halogen, and substituted or unsubstituted (C 1-6 ) alkyl, or both together with the carbon atom to which they are attached form a saturated 3 to 6 member cyclic ring which may optionally include one or more heteroatoms which may be same or different and are selected from O, NR e  and S (where R e  is R z ); 
 Z is selected from CR c , S, O, NR c , R c C═CR c , —N═CR c —, and —R c C═N—; 
 Z 1  is selected from N, NR c  and CR c ; 
 Z 2  and Z 3  are independently selected from C and N; and 
 R c  is absent or selected from hydrogen, hydroxy and halogen. 
 
     
     
         50 . The method of  claim 46 , wherein
 D is   
       
         
           
           
               
               
           
         
         L 2 -Cy 2  is 
       
       
         
           
           
               
               
           
         
       
       (where the squiggly line represents the bond to the bicyclic core in formula (IA-I));
 X 1 , X 2  and X 3  are independently selected from —CR z  and —CR z ═CR z ; 
 Z is selected from CR c , S, O, NR c , R c C═CR c , —N═CR c —, and —R c C═N—; 
 Z 1  is selected from N, NR c  and CR c ; and 
 Z 2  and Z 3  are independently selected from C or N; 
 
       with the proviso that when each occurrence of R 1  and R 2  is hydrogen, and E is —CONH—O—(CR x R y ) p —OR x , then p is not 2. 
     
     
         51 . The method of  claim 46 , wherein the compound of formula (IA-I) is selected from
 2-chloro-N-(2-hydroxyethoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;   2-chloro-N-(2-hydroxyethoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl) benzamide hydrochloride;   2-chloro-N-(2-hydroxyethoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide 4-methylbenzenesulfonate;   2-chloro-N-(2-hydroxyethoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide hydrobromide;   sodium (2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzoyl)(2-hydroxyethoxy)amide;   2-chloro-4-(3-((7-fluoroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N-(2-hydroxyethoxy)benzamide;   2-chloro-4-(3-((7-fluoroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N-(2-hydroxyethoxy)benzamide hydrochloride;   sodium (2-chloro-4-(3-((7-fluoroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzoyl)(2-hydroxyethoxy)amide;   2-chloro-4-(3-((7-fluoro-2-oxo-1,2-dihydroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N-(2-hydroxyethoxy)benzamide;   2,6-difluoro-N-(2-hydroxyethoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;   2,6-difluoro-N-(2-hydroxyethoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide hydrochloride;   sodium (2,6-difluoro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzoyl)(2-hydroxyethoxy)amide;   2,6-difluoro-4-(3-((7-fluoroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N-(2-hydroxyethoxy)benzamide;   2,6-difluoro-4-(3-((7-fluoroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N-(2-hydroxyethoxy)benzamide hydrochloride;   sodium (2,6-difluoro-4-(3-((7-fluoroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzoyl)(2-hydroxyethoxy)amide;   2-fluoro-N-(2-hydroxyethoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;   2-chloro-N-(2-hydroxyethoxy)-4-(3-((2-methylquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;   4-(3-(benzo[d]thiazol-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-2-chloro-N-(2-hydroxyethoxy)benzamide;   4-(3-(benzo[d]thiazol-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-2,6-difluoro-N-(2-hydroxyethoxy)benzamide;   sodium (4-(3-(benzo[d]thiazol-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-2,6-difluorobenzoyl)(2-hydroxyethoxy)amide;   4-(3-(benzo[d]thiazol-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-2-fluoro-N-(2-hydroxyethoxy)benzamide;   2,6-difluoro-N-(2-hydroxyethoxy)-4-(3-((2-methylquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;   2,6-difluoro-N-(2-hydroxyethoxy)-4-(3-((2-methylquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide hydrochloride;   N-(2-hydroxyethoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;   N-(2-hydroxyethoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-2-(trifluoromethyl)benzamide;   4-(3-((7-fluoroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N-(2-hydroxyethoxy)-2-(trifluoromethyl)benzamide;   4-(3-((7-fluoroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N-(2-hydroxyethoxy)-2-(trifluoromethyl)benzamide hydrochloride;   N-(2-hydroxyethoxy)-2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;   N-(2-hydroxyethoxy)-2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide hydrochloride;   N-(2-hydroxyethoxy)-2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide hydrobromide;   N-(2-hydroxyethoxy)-2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide 4-methylbenzenesulfonate;   N-(2-hydroxyethoxy)-2-methyl-4-(3-((2-oxo-1,2-dihydroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;   6-((5-(4-(2-hydroxyethoxycarbamoyl)-3-methylphenyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)methyl)quinoline 1-oxide;   4-(3-((7-fluoroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N-(2-hydroxyethoxy)-2-methylbenzamide;   4-(3-((7-fluoroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N-(2-hydroxyethoxy)-2-methylbenzamide hydrochloride;   2-fluoro-4-(3-((7-fluoroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N-(2-hydroxyethoxy)benzamide;   2-fluoro-4-(3-((7-fluoroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N-(2-hydroxyethoxy)benzamide hydrochloride;   2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl acetate,   (S)-2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl 2-(tert-butoxycarbonylamino)propanoate,   (S)-2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl 2-aminopropanoate,   2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl pivalate,   2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl isobutyrate,   2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl 2-benzamidoacetate,   2-chloro-N-(2-hydroxypropoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   ethyl 2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)acetate,   2-chloro-N-(2-hydroxy-2-methylpropoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   (S)-2-chloro-N-(2-hydroxypropoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   (R)-2-chloro-N-(2-hydroxypropoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   N-(2-hydroxy-2-methylpropoxy)-2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   2,6-difluoro-N-(2-hydroxy-2-methylpropoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   2-fluoro-N-(2-hydroxy-2-methylpropoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   (S)-N-(2-hydroxypropoxy)-2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   N-(2-hydroxy-2-methylpropoxy)-2-methyl-4-(3-((2-oxo-1,2-dihydroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   (R)-N-(2-hydroxypropoxy)-2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   N-(1-hydroxy-2-methylpropan-2-yloxy)-2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   2-chloro-N-(1-hydroxy-2-methylpropan-2-yloxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   N-(2-Hydroxy-2-methyl-propoxy)-2-methyl-4-[3-(1-oxy-quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl]-benzamide,   2-(2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl acetate,   2-(2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl isobutyrate,   2-(2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl pivalate,   2-(2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl benzoate,   2-(2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl furan-2-carboxylate,   
       and pharmaceutically acceptable salts thereof. 
     
     
         52 . The method of  claim 46 , wherein the compound of formula (IA-I) is selected from:
 N-(2-Hydroxy-ethoxy)-2-methyl-4-(3-quinolin-6-ylmethyl-3H-imidazo[4,5-b]pyridin-5-yl)-benzamide;   2-Chloro-N-(2-hydroxy-ethoxy)-4-(3-quinolin-6-ylmethyl-3H-imidazo[4,5-b]pyridin-5-yl)-benzamide;   N-(2-Hydroxy-2-methyl-propoxy)-2-methyl-4-(3-quinolin-6-ylmethyl-3H-imidazo[4,5-b]pyridin-5-yl)-benzamide,   2-Chloro-N-(2-hydroxy-2-methyl-propoxy)-4-(3-quinolin-6-ylmethyl-3H-imidazo[4,5-b]pyridin-5-yl)-benzamide,   
       and pharmaceutically acceptable salts thereof. 
     
     
         53 . A method of inhibiting the proliferative activity of a cell comprising contacting said cell with a compound of formula (IA-I) 
       
         
           
           
               
               
           
         
       
       or a tautomer, stereoisomer, enantiomer, diastereomer, pharmaceutically acceptable salt, or N-oxide thereof; wherein
 X is CR 1  or N; 
 D is monocyclic aryl, wherein D is substituted with a group E which is selected from —CONH—O—(CR x R y ) p —OR x , and —CONH—O—(CR x R y ) p -[cycloalkyl]-(CR x R y ) p —OR x ; and further D can optionally be substituted with one or more of R z ; 
 L 2  is —(CR a R b )—; 
 Cy 2  is substituted or unsubstituted heteroaryl; 
 each occurrence of R 1  and R 2  may be same or different and is independently selected from hydrogen, nitro, hydroxy, cyano, halogen, —OR a , —S(═O) q —R a , —NR a R b , —C(═Y)—R a , —CR a R b —C(═Y)—R a , —CR a R b —Y—CR a R b R b , —C(═Y)—NR a R b , —NR a R b —C(═Y)—NR a R b , —S(═O) q —NR a R b —, —NR a R b —S(═O) q —NR a R b , —NR a R b —NR a R b , substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted C 3-6  cycloalkyl, substituted or unsubstituted C 3-6  cycloalkylalkyl, and substituted or unsubstituted C 3-6  cycloalkenyl; 
 each occurrence of Y is independently selected from O, S, and NR a ; 
 each occurrence of R a  and R b  may be same or different and are independently selected from hydrogen, nitro, hydroxy, cyano, halogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted C 3-6  cycloalkyl, substituted or unsubstituted C 3-6  cycloalkylalkyl, and substituted or unsubstituted C 3-6  cycloalkenyl, or when two R a  and/or R b  substituents are directly bound to a common atom, they may be joined to form a substituted or unsubstituted, saturated or unsaturated 3-10 member ring, which may optionally include one or more heteroatoms which may be same or different and are selected from O, NR c  or S; 
 each occurrence of R c  is independently selected from hydrogen, nitro, hydroxy, cyano, halogen, substituted or unsubstituted C 1-6  alkyl, substituted or unsubstituted C 2-6  alkenyl, substituted or unsubstituted C 2-6  alkynyl, substituted or unsubstituted C 3-6  cycloalkyl, substituted or unsubstituted C 3-6  cycloalkylalkyl, and substituted or unsubstituted C 3-6  cycloalkenyl; 
 each occurrence of R x  and R y  is independently selected from hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, oxo (═O), thio (═S), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted heterocycyl, substituted or unsubstituted heterocyclylalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, —COOR z , —C(O)R z , —C(S)R z , —C(O)NR z R z , —C(O)ONR z R z , —NR z R z , —NR z CONR z R z , —N(R z )SOR z , —N(R z )SO 2 R z , —(═N—N(R z )R z ), —NR z C(O)OR z , —NR z C(O)R z —, —NR x C(S)R y —NR z C(S)NR z R z , —SONR z R z —, —SO 2 NR z R z —, —OR z , —OR z C(O)NR z R z , —OR z C(O)OR z —, —OC(O)R z , —OC(O)NR z R z , —R z NR z C(O)R z , —R z OR z , —R z C(O)OR z , —R z C(O)NR z R z , —R z C(O)R z , —R z OC(O)R z , —SR z , —SOR z , —SO 2 R z , and —ONO 2 , or any two of R x  and R y  which are directly bound to a common atom may be joined to form (i) a substituted or unsubstituted, saturated or unsaturated 3-14 membered ring, which may optionally include one or more heteroatoms which may be the same or different and are selected from O, NR z  or S, or (ii) an oxo (═O), thio (═S) or imino (═NR z ); wherein 
 each occurrence of R z  is independently hydrogen, hydroxy, halogen, carboxyl, cyano, nitro, oxo (═O), thio (═S), substituted or unsubstituted alkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted cycloalkylalkyl, substituted or unsubstituted cycloalkenylalkyl, substituted or unsubstituted heterocycyl, substituted or unsubstituted heterocyclcyalkyl, substituted or unsubstituted aryl, substituted or unsubstituted arylalkyl, substituted or unsubstituted heteroaryl, substituted or unsubstituted heteroarylalkyl, and —ONO 2 , or any two of R z  which are directly bound to a common atom may be joined to form (i) a substituted or unsubstituted, saturated or unsaturated 3-14 membered ring, which may optionally include one or more heteroatoms which may be the same or different and are selected from O, NR′ (where R′ is H or alkyl) or S, or (ii) an oxo (═O), thio (═S) or imino (═NR z ); 
 each occurrence of p independently represents 1, 2, 3, 4, 5, 6, 7 or 8; and 
 each occurrence of q independently represents 0, 1 or 2, 
 
       with the proviso that when Cy 2  is substituted or unsubstituted heteroaryl, each occurrence of R 1  and R 2  is hydrogen, and E is —CONH—O—(CR x R y ) p —OR x , then p is not 2. 
     
     
         54 . The method of  claim 53 , wherein
 D is   
       
         
           
           
               
               
           
         
       
       and
 X 1 , X 2  and X 3  are independently selected from —CR z  and —CR z ═CR z . 
 
     
     
         55 . The method of  claim 53 , wherein
 L 2 -Cy 2  is   
       
         
           
           
               
               
           
         
       
       (where the squiggly line represents the bond to the bicyclic core in formula (IA-I));
 each occurrence of R a  and R b  are independently selected from hydrogen, halogen, and substituted or unsubstituted (C 1-6 ) alkyl, or both together with the carbon atom to which they are attached form a saturated 3 to 6 member cyclic ring which may optionally include one or more heteroatoms which may be same or different and are selected from O, NR e  and S (where R e  is R z ); 
 Z is selected from CR c , S, O, NR c , R c C═CR c , —N═CR c —, and —R c C═N—; 
 Z 1  is selected from N, NR c  and CR c ; 
 Z 2  and Z 3  are independently selected from C or N; and 
 R c  is absent or selected from hydrogen, hydroxy and halogen. 
 
     
     
         56 . The method of  claim 53 ,
 D is E   
       
         
           
           
               
               
           
         
         L 2 -Cy 2  is 
       
       
         
           
           
               
               
           
         
       
       (where the squiggly line represents the bond to the bicyclic core in formula (IA-I));
 X 1 , X 2  and X 3  are independently selected from —CR z  and —CR z ═CR z ; 
 Z is selected from CR c , S, O, NR c , R c C═CR c , —N═CR c —, and —R c C═N—; 
 Z 1  is selected from N, NR c  and CR c ; and 
 Z 2  and Z 3  are independently selected from C and N. 
 
     
     
         57 . The method of  claim 53 , wherein the compound of formula (IA-I) is selected from
 2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl acetate,   (S)-2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl 2-(tert-butoxycarbonylamino)propanoate,   (S)-2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl 2-aminopropanoate,   2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl pivalate,   2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl isobutyrate,   2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl 2-benzamidoacetate,   2-chloro-N-(2-hydroxypropoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   ethyl 2-(2-chloro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)acetate,   2-chloro-N-(2-hydroxy-2-methylpropoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   (S)-2-chloro-N-(2-hydroxypropoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   (R)-2-chloro-N-(2-hydroxypropoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   N-(2-hydroxy-2-methylpropoxy)-2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   2,6-difluoro-N-(2-hydroxy-2-methylpropoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   2-fluoro-N-(2-hydroxy-2-methylpropoxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   (S)-N-(2-hydroxypropoxy)-2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   N-(2-hydroxy-2-methylpropoxy)-2-methyl-4-(3-((2-oxo-1,2-dihydroquinolin-6-yl)methyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   (R)-N-(2-hydroxypropoxy)-2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   N-(1-hydroxy-2-methylpropan-2-yloxy)-2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   2-chloro-N-(1-hydroxy-2-methylpropan-2-yloxy)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide,   N-(2-Hydroxy-2-methyl-propoxy)-2-methyl-4-[3-(1-oxy-quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl]-benzamide,   2-(2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl acetate,   2-(2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl isobutyrate,   2-(2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl pivalate,   2-(2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl benzoate,   2-(2-methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamidooxy)ethyl furan-2-carboxylate,   
       and pharmaceutically acceptable salts thereof. 
     
     
         58 . The method of  claim 53 , wherein the compound of formula (IA-I) is selected from:
 N-(2-Hydroxy-2-methyl-propoxy)-2-methyl-4-(3-quinolin-6-ylmethyl-3H-imidazo[4,5-b]pyridin-5-yl)-benzamide,   2-Chloro-N-(2-hydroxy-2-methyl-propoxy)-4-(3-quinolin-6-ylmethyl-3H-imidazo[4,5-b]pyridin-5-yl)-benzamide,   
       and pharmaceutically acceptable salts thereof.