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 protein kinases

Patent metadata

Field	Value
Publication number	US-2017240542-A1
Application number	US-201715454760-A
Country	US
Kind code	A1
Filing date	Mar 9, 2017
Priority date	May 17, 2010
Publication date	Aug 24, 2017
Grant date	—

Abstract

The present invention provides, inter alia, compounds of formula I as protein kinase modulators, methods of preparing them, pharmaceutical compositions containing them and methods of treatment, prevention and/or amelioration of kinase mediated diseases or disorders with them.

First claim

1 .- 66 . (canceled)

67 . A method of inhibiting the HGF/c-Met kinase signalling pathway in a cell comprising contacting the cell with a compound of formula (IA-1):

or a tautomer, stereoisomer, enantiomer, diastereomer, salt, or N-oxide thereof, wherein
X is N;
Cy2 is selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
D is phenyl substituted with one to five substituents selected from halogen, substituted or unsubstituted alkyl, and —CONR x R y ;
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 z C(S)R z —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 );
each occurrence of R z 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 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 );
R 2 is hydrogen; and
L 2 is substituted or unsubstituted alkyl.

68 . A method of inhibiting the proliferative activity of a cell comprising contacting the cell with a compound of formula (IA-1):

or a tautomer, stereoisomer, enantiomer, diastereomer, salt, or N-oxide thereof, wherein
X is N;
Cy2 is selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic group, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl;
D is phenyl substituted with one to five substituents selected from halogen, substituted or unsubstituted alkyl, and —CONR x R y ;
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 z C(S)R z —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 );
each occurrence of R z 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 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 );
R 2 is hydrogen; and
L 2 is substituted or unsubstituted alkyl.

69 . The method of claim 68 , wherein D is selected from

70 . The method of claim 68 , wherein the substituted or unsubstituted alkyl in L 2 is —CR a CR b —, wherein
each occurrence of R a and R b may be the same or different and are independently selected from hydrogen, nitro, hydroxy, cyano, halogen, substituted or unsubstituted C 1-6 alkyl, s

Assignees

• Incozen Therapeutics Pvt Ltd
• Rhizen Pharmaceuticals Sa

Inventors

• Muthuppalaniappan Meyyappan
• Viswanadha Srikant
• Babu Govindarajulu
• Vakkalanka Swaroop K

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title