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-10087182-B2
Application number	US-201715454760-A
Country	US
Kind code	B2
Filing date	Mar 9, 2017
Priority date	May 17, 2010
Publication date	Oct 2, 2018
Grant date	Oct 2, 2018

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

The invention claimed is:

1. 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;
Cy 2 is selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocyclic group, substituted 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 (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 (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 heterocyclyalkyl, 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 —(CR a R b ) n —;

wherein
each occurrence of R a and R b may be the same or different and are independently selected from hydrogen, and methyl;
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 cycloralkylalkyl, and substituted or unsubstituted C 3-6 cycloalkenyl; and
n is 1.

2. The method of claim 1 , wherein D is selected from

3. The method of claim 1 , wherein
each occurrence of R a and R b is hydrogen.

4. The method of claim 1 , wherein L 2 is —CH 2 —, —CH(CH 3 )— or —C(CH 3 ) 2 —.

5. The method of claim 1 , wherein L 2 is —CH 2 — or —CH(CH 3 )—.

6. The method of claim 1 , wherein Cy 2 is substituted aryl or substituted or unsubstituted bicyclic heteroaryl.

7. The method of claim 1 , wherein Cy 2 is selected from

8. The method of claim 1 , wherein Cy 2 is selected from

9. The method of claim 1 , wherein the compound of formula (IA-1) is selected from
(3-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)phenyl)methanol;
(4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)phenyl)methanol;
N-Methyl-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;
2-Fluoro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;
(2-Fluoro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)phenyl)methanol;
N-(2-Hydroxyethyl)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;
4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;
(4-Methylpiperazin-1-yl)(4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)phenyl)methanone;
N-(2-(dimethylamino)ethyl)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;
4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N-(tetrahydro-2H-pyran-4-yl)benzamide;
tert-Butyl 4-(4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamido)piperidine-1-carboxylate;
N-(Piperidin-4-yl)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide hydrochloride;
N-(2-(dimethylamino)ethyl)-2-fluoro-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]-triazolo[4,5-b]pyridin-5-yl)benzamide;
(S)-(2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-yl)(4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)phenyl)methanone hydrochloride;
(4-(2-hydroxyethyl)piperazin-1-yl)(4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)phenyl)methanone;
(R)-(3-hydroxypyrrolidin-1-yl)(4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)phenyl)methanone hydrochloride;
N-(2-(piperidin-1-yl)ethyl)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo-[4,5-b]pyridin-5-yl)benzamide;
N-(2-morpholinoethyl)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;
N-(2-(pyrrolidin-1-yl)ethyl)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;
(4-(pyrrolidin-1-yl)piperidin-1-yl)(4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]-triazolo[4,5-b]pyridin-5-yl)phenyl)methanone;
N-(3-(dimethylamino)propyl)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)benzamide;
N,N-Bis(2-methoxyethyl)-4-(3-(quinolin-6-ylmethyl)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-

Assignees

• Incozen Therapeutics Pvt Ltd
• Rhizen Pharmaceuticals Sa

Inventors

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

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/08

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

• A61P37/02

  Immunomodulators · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P35/00

  Antineoplastic agents · CPC title