Substituted azaindazole compounds

Patent metadata

Field	Value
Publication number	US-9266880-B2
Application number	US-201113884676-A
Country	US
Kind code	B2
Filing date	Nov 9, 2011
Priority date	Nov 12, 2010
Publication date	Feb 23, 2016
Grant date	Feb 23, 2016

Abstract

Disclosed are azaindazole compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein: Q is: (i) 5-membered heteroaryl comprising at least one nitrogen heteroatom and substituted with zero to 2 Rg; or (ii) 9- to 10-membered bicyclic heteroaryl selected from Formula (II) and; wherein Ring A is a 5- to 6-membered aryl or heteroaryl fused ring substituted with zero to 2 Rg; and R1, R2, R3, and Rg are defined herein. Also disclosed are methods of using such compounds in the treatment of at least one CYP17 associated condition, such as, for example, cancer, and pharmaceutical compositions comprising such compounds.

First claim

What is claimed is:

1. A compound of Formula (I):

or pharmaceutically acceptable salts thereof, wherein:
Q is:
(i) 5-membered heteroaryl comprising at least one nitrogen heteroatom and substituted with zero to 2 R g ; or
(ii) 9- to 10-membered bicyclic heteroaryl selected from

wherein Ring A is a 5- to 6-membered aryl or heteroaryl fused ring substituted with zero to 2 R g ;
R 1 is:
(i) H, halo, —CN, —OR d , —NR e R e , or —C(O)OR f ;
(ii) C 1-6 alkyl substituted with zero to 4 R a ;
(iii) C 3-6 cycloalkyl substituted with zero to 4 R a ;
(iv) aryl substituted with zero to 6 R b ;
(v) heterocyclyl substituted with zero to 6 R c ; or
(vi) heteroaryl substituted with zero to 6 R c ;

R 2 is:
(i) C 1-6 alkyl substituted with zero to 4 R a ′ where each R a ′ is independently halo, —OH, —CN, C 3-6 cycloalkyl, C 1-2 fluoroalkyl, C 1-6 alkoxy, C 1-2 fluoroalkoxy, —NR f R f , phenoxy substituted with zero to 4 R b , heterocyclyl substituted with zero to 4 R c , and/or heteroaryl substituted with zero to 4 R b ;
(ii) C 3-6 cycloalkyl substituted with zero to 4 R a ;
(iii) —S(O) 2 (C 1-4 alkyl), —S(O) 2 (C 1-4 fluoroalkyl), or —C(O)(C 1-6 alkyl);
(iv) aryl substituted with zero to 6 R b ;
(v) heterocyclyl substituted with zero to 6 R c ; or
(vi) heteroaryl substituted with zero to 6 R c ;

each R a is independently halo, —OH, —CN, C 3-6 cycloalkyl, C 1-2 fluoroalkyl, C 1-6 alkoxy, C 1-2 fluoroalkoxy, —NR f R f , phenyl substituted with zero to 5 R b , phenoxy substituted with zero to 4 R b , heterocyclyl substituted with zero to 4 R c , and/or heteroaryl substituted with zero to 4 R b ;
each R b is independently halo, —OH, —CN, C 1-4 alkyl, C 3-6 cycloalkyl, C 1-2 fluoroalkyl, C 1-6 alkoxy, C 1-4 fluoroalkoxy, —NR f R f , —C(O)OH, —S(O) 2 (C 1-4 alkyl), —S(O) 2 NR f R f , and/or heterocyclyl substituted with zero to 4 R c ;
each R c is independently halo, —CN, —OH, C 1-4 alkyl, C 3-6 cycloalkyl, C 1-2 fluoroalkyl, C 1-6 alkoxy, C 1-4 fluoroalkoxy, —NR f R f , azetidine, and/or pyrrolidine, or two R c attached to the same atom can form ═O;
each R d is:
(i) C 1-4 alkyl substituted with zero to 4 R a ;
(ii) C 3-6 cycloalkyl substituted with zero to 4 R a ;
(iii) aryl substituted with zero to 6 R b ;
(iv) heterocyclyl substituted with zero to 6 R c ; and/or
(v) heteroaryl substituted with zero to 6 R c ;

each R e is independently:
(i) H;
(ii) C 1-4 alkyl substituted with zero to 4 R a ; and/or
(iii) C 3-6 cycloalkyl substituted with zero to 4 R a ;

or two R e attached to the same nitrogen atom can form a 5-6 membered heterocyclyl ring having one additional heteroatom, and substituted with zero to 2 substituents independently selected from —CN, —OH, and/or C 1-4 alkyl:
each R f is independently H, C 1-6 alkyl, C 3-6 cycloalkyl, C 1-4 fluoroalkyl, and/or aryl; and
each R g is independently:
(i) halo, —CN, —OR d , —NR e R e , or —C(O)OR f ;
(ii) C 1-6 alkyl substituted with zero to 4 R a ;
(iii) C 3-6 cycloalkyl substituted with zero to 4 R a ;
(iv) aryl substituted with zero to 6 R b ;
(v) heterocyclyl substituted with zero to 6 R c ; or
(vi) heteroaryl substituted with zero to 6 R c .

2. The compound according to claim 1 or pharmaceutically acceptable salts thereof, wherein Q is an imidazolyl substituted with zero to 2 R g .

3. The compound according to claim 2 or pharmaceutically acceptable salts thereof, wherein Q is:

4. The compound according to claim 1 or pharmaceutically acceptable salts thereof, wherein Q is a 9- to 10-membered bicyclic heteroaryl selected from

wherein Ring A is a 5- to 6-membered aryl or heteroaryl fused ring substituted with zero to 2 R g .

5. The compound according to claim 4 or pharmaceutically acceptable salts thereof, wherein Q is:

6. The compound according to claim 1 or pharmaceutically acceptable salts thereof, wherein Q is

7. The compound according to claim 1 or pharmaceutically acceptable salt thereof, wherein said compound is selected from 4-(1-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)isoquinoline (1); 1-(4-fluorophenyl)-4-(1H-imidazol-1-yl)-1H-pyrazolo[3,4-b]pyridine (2); 5-(1-(4-fluorophenyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)-1,7-naphthyridine (3); 1-(4-fluorophenyl)-4-(1-methyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-b]pyridine (4); 3-(4-(1,7-naphthyridin-5-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)benzenesulfonamide (5); 3-(4-(1-methyl-1H-imidazol-5-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)benzenesulfonamide (6); 3-(4-(isoquinolin-4-yl)-1H-pyrazolo[3,4-b]pyridin-1-yl)benzenesulfonamide (7); and 1-(2,4-difluorophenyl)-4-(pyrrolo[1,2-c]pyrimidin-4-yl)-1H-pyrazolo[3,4-b]pyridine (8).

8. A pharmaceutical composition, comprising a pharmaceutically acceptable carrier and a compound according to claim 1 or pharmaceutically acceptable salts thereof.

9. The compound according to claim 1 or pharmaceutically acceptable salts thereof, wherein Q is pyrrolyl, imidazolyl, isoxazolyl, oxazolyl, isothiazolyl, triazolyl or oxadiazolyl, each of which is substituted with zero to 2 R g .

10. The compound according to claim 6 or pharmaceutically acceptable salts thereof, wherein:
R 1 is H; and
R 2 is fluorophenyl, difluorophenyl, or phenyl substituted with —SO 2 NH 2 .

11. The compound according to claim 4 or pharmaceutically acceptable salts thereof, wherein Q is pyrrolo[1,2-c]pyrimidinyl, isoquinolinyl, 4aH-pyrido[1,2-c]pyrimidinyl, 1,6-naphthyridinyl, or 1,7-naphthyridinyl.

12. The compound according to claim 1 , wherein R 1 is:
(i) H, F, Cl, —CN, —OH, —OCH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , —COOH, or —COOCH 3 ;
(ii) C 1-6 alkyl substituted with zero to 4 R a , in which R a is independently —CH 2 F, —CF 3 , and/or C 3-6 cycloalkyl;
(iii) C 3 -C 6 cycloalkyl substituted with zero to 4 R a ;
(iv) phenyl substituted with zero to 3 R b groups, where R b is independently selected from F, Cl, —CN, —CH 3 , —CF 3 , —OCH 3 , —OCF 3 , —NH 2 , and/or —SO 2 NH 2 ;
(v) azetidinyl, tetrahydrofuranyl, pyrrolidinyl, tetrahydropyranyl, piperidinyl, morpholinyl, or piperazinyl, each of which is substituted with zero to 6 R c ; or
(vi) pyrrolyl, furanyl, pyrazolyl, imidazolyl, isoxazolyl, oxazolyl, thiazolyl, triazolyl, oxadiazolyl, pyridinyl, pyridazinyl, pyrimidinyl, or pyrazinyl, each of which is substituted with zero to 3 R c .

13. The compound according to claim 1 or pharmaceutically acceptable salts thereof wherein R 2 is:
(i) C 1-4 alkyl substituted with zero to 4 R a ′;
(ii) C 3-6 cycloalkyl substituted with zero to 4 R a ;
(iii) —S(O) 2 (C 1-2 alkyl), —S(O) 2 (C 1-2 fluoroalkyl), or C(O)(C 1-3 alkyl);
(iv) phenyl substituted with zero to 4 R b independently selected from F, Cl, —CN, —OH, —CH 3 , —CF 3 , —OCH 3 , —OCF 3 , —NH 2 , and/or —SO 2 NH 2 ;
(v) azetidinyl, tetrahydrofuranyl, pyrrolidinyl, tetrahydropyranyl, piperidinyl, morpholinyl, or piperazinyl, each of which is substituted with zero to 6 R c ; or
(vi) pyrrolyl, furanyl,

Assignees

• Austin Joel F
• Frennesson David B
• Saulnier Mark G
• Bristol Myers Squibb Co

Inventors

• Austin Joel F
• Frennesson David B
• Saulnier Mark G

Classifications

• C07D487/04

  Ortho-condensed systems · CPC title

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• A61P35/00

  Antineoplastic agents · CPC title