IP Library Granted Patent US 8,623,889
Granted Patent B2
US 8,623,889 · App. 13/325,751 · Granted Jan 7, 2014

Substituted 6,6-fused nitrogenous heterocyclic compounds and uses thereof

Inventors: Joseph P. Lyssikatos (Piedmont, CA); Lewis J. Gazzard (Belmont, CA); Emily Hanan (Redwood City, CA); Samuel Kintz (Redwood City, CA); Hans Edward Purkey (Burlingame, CA)
Assignee: Genentech, Inc.
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Quick Facts
Patent No.
US 8,623,889
App. No.
13/325,751
Granted
Jan 7, 2014
Kind
B2
Abstract

The invention provides novel compounds having the general formula: wherein X 1 is N or N + O − , and one of X 2 , X 3 and X 4 is N or N + —O − and the remainder of X 2 , X 3 and X 4 is C. R 2 , R 3 , R 4 , R 5 , R 6 . A, B and Y are as described herein. Additionally compositions compounds of Formula I and methods of use are further described herein.

Claims (440)

1. Compounds of formula (I)

or pharmaceutically acceptable salts thereof, having the subformula Ia, Ib or Id selected from the group consisting of:

or an N-oxide thereof,

wherein:

Y is absent or is selected from the group consisting of —C(═O)—, —N(H)C(═O)—, —N(R a )C(═O)—, —O—C(═O)—, —N(H)S(O) 1-2 —, —N(R a )S(O) 1-2 — and —S(O) 2 —, wherein R a is selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 heteroalkyl, C 2-6 alkenyl and C 2-6 alkynyl;

R 2 is —(X b ) 0-1 —R b , wherein X b is selected from the group consisting of C 1-6 alkylene, C 2-6 alkenylene, C 2-6 alkynylene, C 1-6 heteroalkylene, 3-6 membered cycloalkylene and 3-6 membered heterocycloalkylene, R b is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, 3-6 membered cycloalkyl, 3-6 membered heterocycloalkyl, 6-10 membered aryl and 5-10 membered heteroaryl, wherein the aliphatic and aromatic portions of X b and R b are each independently optionally substituted with 1 to 5 R b1 substituents selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, F, Cl, Br, I, —OH, —NH 2 , —SH, —CN, —NO 2 , —N 3 , —C(═O)OH, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 dialkylamino, —(C 1-4 alkenylene) 0-1 -C(═O)—(C 1-4 alkyl), —(C 1-4 alkenylene) 0-1 -C(═O)O—(C 1-4 alkyl), —(C 1-4 alkenylene) 0-1 -C(═O)N(H)—(C 1-4 alkyl), —(C 1-4 alkenylene) 0-1 -C(═O)N(C 1-4 alkyl) 2 , —(C 1-4 alkenylene) 0-1 -S(O) 2 —(C 1-4 alkyl), —(C 1-4 alkenylene) 0-1 -C(═O)—(C 1-4 heteroalkyl) and —(C 1-4 alkenylene) 0-1 -C(═O)—(C 3-6 heterocycloalkyl), and wherein if R b is a 6 membered aryl or a 5-6 membered heteroaryl then any two substituents attached to adjacent atoms said aryl or heteroaryl are optionally combined to from a 3-6 membered carbocyclic or a 3-6 membered heterocyclic ring comprising 1-3 heteroatoms selected from N, O and S, and optionally substituted with 1 to 3 R b1 substituents;

X 1 is N or N + —O − ;

X 2 , X 3 and X 4 are each C, or one of X 2 , X 3 and X 4 is N or N + —O − and the remainder of X 2 , X 3 and X 4 are each C;

R 3 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 dialkyamino, F, Cl, Br, I, —CN, —CF 3 , —OCF 3 , —SF 5 and —N 3 ;

R 4 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, F, Cl, Br, I, —CN, —NO 2 , —N 3 , —SH, —OH, C 1-6 alkoxy, —CF 3 , —OCF 3 , —SF 5 , C 1-6 alkylamino and C 1-6 dialkylamino, or is absent if X 4 is N or N + —O;

R 5 is (X c ) 0-1 —R c , wherein X c is selected from the group consisting of C 1-6 alkylene, C 2-6 alkenylene, C 2-6 heteroalkylene, C 2-6 alkynylene, —N(H)—, —N(R xc )—, —O—, —S(O) 2 —, —C(═O)—, —C(═O)O—, —C(═O)N(H)—, —N(H)C(═O)— and —OC(═O)—, wherein R xc is selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, and wherein R c is selected from the group consisting of hydrogen, F, Cl, Br, I, —CN, —NO 2 , —NH 2 , —OH, —CF 3 , —OCF 3 , —SF 5 , C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 dialkylamino, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, 3-6 membered cycloalkyl, 3-6 membered heterocycloalkyl, 6 membered aryl and 5-6 membered heteroaryl, wherein the aliphatic and aromatic portions of X c and R c are optionally substituted with 1 to 5 R c1 substituents selected from the group consisting of C 1-6 alkyl, C 1-6 heteroalkyl, F, Cl, Br, I, —OH, —NH 2 , —SH, —CN, —NO 2 , —N 3 , —C(═O)OH, —N(C 1-6 alkyl) 2 , —NH(C 1-6 alkyl), —O(C 1-6 alkyl), —(C 1-4 alkenylene) 0-1 -C(═O)—(C 1-4 alkyl), —(C 1-4 alkenylene) 0-1 -C(═O)O—(C 1-4 alkyl), —(C 1-4 alkenylene) 0-1 -C(═O)N(H)—(C 1-4 alkyl), —(C 1-4 alkenylene) 0-1 -C(═O)N(C 1-4 alkyl) 2 , —(C 1-4 alkenylene) 0-1 -S(O) 2 —(C 1-4 alkyl), —(C 1-4 alkenylene) 0-1 -C(═O)—(C 1-4 heteroalkyl) and —(C 1-4 alkenylene) 0-1 -C(═O)—(C 3-6 heterocycloalkyl), or R 5 is absent if X 3 is N or N + —O − ;

R 6 is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 dialkylamino, C 2-6 alkenyl, C 2-6 alkynyl, F, Cl, Br, I, —OH, —NH 2 , —SH, —CN, —NO 2 , —CF 3 , —OCF 3 , —SF 5 and —N 3 , or R 6 is absent if X 2 is N or N + —O − ;

A is absent or is selected from the group consisting of —O—, —N(H)—, —N(R d )—, —S(O) 2 —, —S(O)—, —S—, —(X d ) 0-1 —N(H)C(═O)—, —(X d ) 0-1 —N(R d )C(═O)—, —X d —, —(X d ) 0-1 —C(═O)N(H)—, —(X d ) 0-1 —C(═O)N(R d )—, —(X d ) 0-1 —C(═O)—, —C(═O)—(X d ) 0-1 —, —(X d ) 0-1 —OC(═O)— and —(X d ) 0-1 C(═O)O—, wherein X d is selected from the group consisting of C 1-6 alkylene, C 2-6 alkenylene, C 2-6 alkynylene, C 1-6 heteroalkylene, 6-10 membered arylene, 5-10 membered heteroarylene, 3-10 membered cycloalkylene, 3-10 membered heterocycloalkylene, and R d at each occurrence is independently selected from the group consisting of C 1-6 alkyl, C 2-6 alkenyl, C 1-6 heteroalkyl and C 1-6 haloalkyl, wherein the aliphatic or aromatic portions of X d and R d are each independently optionally substituted with 1 to 5 R d1 substituents selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkylamino, C 1-6 dialkylamino, F, Cl, Br, I, —OH, —NH 2 , —SH, —CN, —NO 2 , —CF 3 , —OCF 3 , —SF 5 , and —N 3 ;

B is selected from the group consisting of 3-6 membered cycloalkyl, 4-9 membered heterocycloalkyl, 6-10 membered aryl and 5-6 membered heteroaryl, wherein the aliphatic or aromatic portions of B are independently optionally substituted with 1 to 5 R B1 substituents selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 dialkylamino, C 3-6 heterocycloalkyl, F, Cl, Br, I, —OH, —NH 2 , —SH, —CF 3 , —OCF 3 , —SF 5 , —(X e ) 0-1 —CN, —(X e ) 0-1 —NO 2 , —(X e ) 0-1 —N 3 , —(X e ) 0-1 —OH, —(X e ) 0-1 —H, —(X e ) 0-1 —N(H)R e , —(X e ) 0-1 —N(R e ) 2 , —(X e ) 0-1 —SR e , —(X e ) 0-1 —C(O)R e , —(X e ) 0-1 —S(O) 2 R e , —(X e ) 0-1 —S(O)R e , —N(H)S(O) 2 R e , —N(R e )S(O) 2 R e , —(X e ) 0-1 —C(═O)OR e , —(X e ) 0-1 —C(═O)OH, —(X e ) 0-1 —C(═O)N(H)R e , —(X e ) 0-1 —C(═O)N(R e )R e , —(X e ) 0-1 —N(H)C(═O)R e , —(X e ) 0-1 —N(R e )C(═O)R e , wherein if B is a 6 membered aryl or a 5-6 membered heteroaryl then any two substituents attached to adjacent atoms of said aryl or heteroaryl are optionally combined to from a 3-6 membered carbocyclic or a 3-6 membered heterocyclic ring optionally comprising 1-3 heteroatoms selected from N, O and S, and optionally substituted with 1 to 3 R B1 substituents; wherein X e is selected from the group consisting of C 1-6 alkylene, C 2-6 alkenylene, C 2-6 alkynylene, C 1-6 heteroalkylene, C 3-6 cycloalkylene and C 3-6 heterocycloalkylene, and R e at each occurrence is independently selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, 3-7 membered cycloalkyl, 3-7 membered heterocycloalkyl, phenyl and 5-6 membered heteroaryl, wherein the aliphatic or aromatic portions of X e and R e are each independently optionally substituted with 1 to 5 R e1 substituents selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkylamino, C 1-6 dialkylamino, F, Cl, Br, I, —OH, —NH 2 , —SH, —CN, —NO 2 , —CF 3 , —OCF 3 , —SF 5 and —N 3 , and wherein any two R e groups attached to the same nitrogen atom are optionally combined to form a 3-7 membered heterocyclic or 5-10 membered heteroaryl ring comprising 1-3 heteroatoms selected from N, O and S; and

wherein if X 3 is N, R 3 is H, R 4 is H or NH 2 , R 6 is —OH and —Y—R 2 is other than H, then -A-B is not thiazol-4-yl substituted with 2-thiophenyl-S(O) 2 CH 2 —, phenyl-S(O) 2 —CH 2 —, 4-pyridyl, or pyridyl-S(O) 2 CH 2 —, if X 3 is N, R 3 is H or Cl, R 4 is H, R 6 is —OH, —NH 2 , or —NHCH 3 and —Y—R 2 is hydrogen, 4-tetrahydropyranyl, 4-((CH 3 CH 2 ) 2 N(CH 2 ) 3-4 O)-phenyl, (CH 3 CH 2 ) 2 N(CH 2 ) 4 —, 3-(4-methylpiperazinyl)-propyl or trifluoroacetyl, then -A-B is not 2-chlorophenyl, 2-methylphenyl, 2,6-dichlorophenyl, 3,5-dimethoxyphenyl, 3,4-dimethoxypheny, phenyl, 2-chloro-6-(2-ethoxyethoxy)phenyl, if X 3 is N, R 3 , R 4 and R 6 are each H, and —Y—R 2 is hydrogen, cyclohexyl, (CH 3 CH 2 ) 2 NCH 2 CH 2 —, CH 3 N(H)CH 2 CH 2 —, (CH 3 ) 2 NCH 2 CH 2 —, (CH 3 ) 3 CC(═O)— or 2-(4-morpholinyl)ethyl, then -A-B is not 3,4-dimethoxyphenyl or optionally substituted pyridine-2-on-3-yl, if X 4 is N, R 3 is H, R 5 is isopropyl, R 6 is methoxy, -A-B is propyl or isopropyl, then —Y—R 2 is other than optionally substituted pyridyl, if X 4 is N, R 3 , R 5 , R 6 are each H, -A-B is methyl, then —Y—R 2 is other than hydrogen, if R 3 , R 4 , R 5 and R 6 are each H, and —Y—R 2 is hydrogen, cyclohexyl, (CH 3 CH 2 ) 2 NCH 2 CH 2 —, CH 3 N(H)CH 2 CH 2 —, (CH 3 ) 2 NCH 2 CH 2 —, (CH 3 ) 3 CC(═O)— or 2-(4-morpholinyl)ethyl, then -A-B is not 3,4-dimethoxyphenyl or optionally substituted pyridine-2-on-3-yl, if R 3 , R 4 and R 5 are each hydrogen, —Y—R 2 is other than hydrogen, then one of R 6 and -A-B is other than ethoxy.

2. The compound of claim 1 , wherein R 3 , R 4 and R 6 , if present, are each independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, —CF 3 , —OCF 3 , —SF 5 , F, Cl, Br and I.

3. The compound of claim 1 , wherein in R 2 , X b is absent or is selected from C 1-6 alkylene and 3-6 membered cycloalkylene; and R b is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 2-6 alkenyl, C 2-6 alkynyl, 3-6 membered cycloalkyl, 3-6 membered heterocycloalkyl, 6-10 membered aryl, and 5-10 membered heteroaryl, wherein X b and R b are each independently optionally substituted.

4. The compound of claim 3 , wherein in R 2 , X b is absent.

5. The compound of claim 3 , wherein in R 2 , R b is selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 2-6 alkenyl and C 2-6 alkynyl.

6. The compound of claim 3 , wherein in R 2 , R b is optionally substituted with from 1 to 5 R b1 groups selected from the group consisting of F, Cl, Br, I, OH, NH 2 , SH, CN, NO 2 , C 1-6 alkoxy, C 1-6 alkylamino and C 1-6 dialkylamino.

7. The compound of claim 1 , wherein in R 2 , R b is selected from the group consisting of cycloprop-1-yl, cyclobut-1-yl, cyclopent-1-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridin-2-yl, pyridin-4-yl, pyridin-3-yl, pyridin-2-on-6-yl, pyridine-2-on-5-yl, pyridine-2-on-4-yl, pyridine-2-on-3-yl, cyclohex-1-yl, phenyl, 4,5-dihydrooxazol-2-yl, oxazol-2-yl, piperidin-4-yl, piperidin-3-yl, piperidin-2-yl, piperidin-1-yl, piperazin-1-yl, piperazin-2-yl, piperazin-3-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, tetrahydropyran-4-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, oxetan-3-yl, oxetan-2-yl, pyrazol-5-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, tert-butyl, pyrrolidin-3-yl, pyrrolidin-2-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl and 3-oxabicyclo[3.1.0]hexan-6-yl, wherein said R b is further optionally substituted.

8. The compound of claim 1 , wherein Y is absent or is selected from the group consisting of —C(═O)—, —N(H)C(═O)—, —N(R a )C(═O)— and —S(O) 2 —.

9. The compound of claim 8 , wherein in R 2 , R b is selected from the group consisting of cycloprop-1-yl, cyclobut-1-yl, cyclopent-1-yl, pyrimidin-2-yl, pyrimidin-4-yl, pyrimidin-5-yl, pyridin-2-yl, pyridin-4-yl, pyridin-3-yl, pyridin-2-on-6-yl, pyridine-2-on-5-yl, pyridine-2-on-4-yl, pyridine-2-on-3-yl, cyclohex-1-yl, phenyl, 4,5-dihydrooxazol-2-yl, oxazol-2-yl, piperidin-4-yl, piperidin-3-yl, piperidin-2-yl, piperidin-1-yl, piperazin-1-yl, piperazin-2-yl, piperazin-3-yl, morpholin-2-yl, morpholin-3-yl, morpholin-4-yl, tetrahydropyran-4-yl, tetrahydropyran-2-yl, tetrahydropyran-3-yl, oxetan-3-yl, oxetan-2-yl, pyrazol-5-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, methyl, ethyl, propyl, isopropyl, butyl, iso-butyl, tert-butyl, pyrrolidin-3-yl, pyrrolidin-2-yl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl and 3-oxabicyclo[3.1.0]hexan-6-yl, and wherein in R 2 , R b is optionally substituted.

10. The compound of claim 9 , wherein the Y is —C(═O)—.

11. The compound of claim 7 , wherein in R 2 , R b is selected from the group as set forth on FIG. 1-A and FIG. 1-B .

12. The compound of claim 1 , wherein A is absent.

13. The compound of claim 1 , wherein A is present is selected from the group consisting of O—, —N(H)—, —N(R d )—, —S(O) 2 —, —S(O)— and —S—.

14. The compound of claim 1 , wherein A is present and is selected from the group consisting of —(X d ) 0-1 —N(H)C(═O)—, —(X d ) 0-1 —N(R d )C(═O)—, —X d —, —(X d ) 0-1 —C(═O)N(H)—, —(X d ) 0-1 —C(═O)N(R d )—, —(X d ) 0-1 —C(═O)—, —C(═O)—(X d ) 0-1 —, —(X d ) 0-1 —OC(═O)—, —(X d ) 0-1 C(═O)O— and wherein the X d group in A is selected from the group consisting of C 1-6 alkylene, C 2-6 alkenylene C 1-6 heteroalkylene, 6-10 membered arylene and a 5-10 membered heteroarylene comprising 1 to 3 heteroatoms selected from N, O and S, wherein said X d is optionally substituted.

15. The compound of claim 14 , wherein the X d group in A is selected from the group consisting of phenylene, pyridylene, pyrimidinylene, pyridazinylene, pyrazinylene, and wherein said X d is optionally substituted.

16. The compound of claim 15 , wherein A is selected from the group consisting of

17. The compound of claim 1 , wherein A is selected from the group consisting of:

18. The compound of claim 1 , wherein B is selected from the group consisting of phenyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrrolidin-3-yl, pyrazol-1-yl, pyrazol-3-yl, pyrazol-4-yl, pyrazol-5-yl, thiazol-2-yl, thiazol-4-yl, thiazol-5-yl, pyridin-4-on-3-yl, pyridin-4-on-2-yl, pyridin-4-on-1-yl, pyridin-2-on-1-yl, pyridin-2-on-3-yl, pyridin-2-on-4-yl, pyrrol-1-yl, pyrrol-3-yl, pyrrol-4-yl, pyridazin-3-yl, pyridazin-4-yl, pyridazin-5-yl, pyrazin-2-yl, cyclohexyl, cyclobutyl, cyclopropyl, cyclopentyl, morpholin-4-yl, morpholin-2-yl, morpholin-3-yl, piperazin-1-yl, piperazin-2-yl, cyclopentyl, piperidin-1-yl, piperidin-4-yl, piperidin-2-yl, piperidin-3-yl, indol-5-yl, indol-4-yl, indol-3-yl, indol-2-yl, pyridimdin-5-yl, pyridimdin-4-yl, pyrimidin-2-yl, indazol-3-yl, indazol-4-yl, indazol-5-yl, indazol-6-yl, indazol-7-yl, indolin-2-on-4-yl, indolin-2-on-5-yl, indolin-2-on-6-yl, indolin-2-on-7-yl, tetrahydropyran-4-yl, tetrahydropyran-3-yl, tetrahydropyran-2-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, tetrahydrofuran-4-yl, wherein B is optionally substituted and wherein any two substituent located on adjacent atoms of B are optionally combined to form an optionally substituted 5 to 7 membered heterocyclic ring comprising 1 to 3 heteroatoms selected from N, O and S.

19. The compound of claim 15 , wherein B is selected from the group consisting of phenyl, pyridin-2-yl, pyridin-3-yl and pyridin-4-yl, wherein the B is optionally substituted with 1 to 3 R B1 substitutents selected from the group consisting of C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 dialkylamino, F, Cl, Br, I, —OH, —NH 2 , —SH, —(X e ) 0-1 —CN, —(X e ) 0-1 —NO 2 , —(X e ) 0-1 —N 3 , —(X e ) 0-1 —N(H)R e , —(X e ) 0-1 —N(R e ) 2 , —(X e ) 0-1 —SR e , —(X e ) 0-1 —C(O)R e , —(X e ) 0-1 —S(O) 2 R e , —(X e ) 0-1 —S(O)R e , —(X e ) 0-1 —C(═O)OR e , —(X e ) 0-1 —C(═O)N(H)R e , —(X e ) 0-1 —C(═O)N(R e )R e , —(X e ) 0-1 —N(H)C(═O)R e and —(X e ) 0-1 —N(R e )C(═O)R e , and wherein any two substituent located on adjacent atoms of B are optionally combined to form an optionally substituted 5 to 7 membered heterocyclic ring comprising 1 to 3 heteroatoms selected from N, O and S.

20. The compound of claim 17 , wherein B is selected from the group consisting of

21. The compound of claim 1 , wherein B is selected from the group consisting of:

22. The compound of claim 1 , wherein R 5 is (X c )—R c , wherein X c is absent or is selected from the group consisting of C 1-6 alkylene, —N(H)—, —N(R xc )—, —O—, —S(O) 2 —, and R c is selected from the group consisting of hydrogen, F, Cl, Br, I, —CN, —NO 2 , —CF 3 , —OCF 3 , —SF 5 , C 1-6 alkyl, C 1-6 heteroalkyl, piperidin-1-yl, piperidin-2-yl, piperidin-3-yl, piperidin-4-yl, cyclopropyl, cyclopentyl, phenyl, pyridin-2-yl, pyridin-3-yl, pyridine-4-yl, pyrazol-4-yl, pyrazol-5-yl, thiazol-2-yl, thiazol-3-yl, thiazol-5-yl, piperazin-1yl, piperazin-2-yl, pyrrolidin-1-yl, pyrrolidin-2-yl, pyrroldin-3-yl, tetrahydrofuran-2-yl, tetrahydrofuran-3-yl, wherein R c is optionally substituted.

23. A compound of formula I selected from the group consisting of:

N-(7-(piperidin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

7-(2-chlorophenyl)-N-(pyrimidin-2-yl)isoquinolin-3-amine;

7-(2-chlorophenyl)-N-(pyridin-2-yl)isoquinolin-3-amine;

7-(2-chloro-5-fluorophenyl)-N-(methylthiomethyl)isoquinolin-3-amine;

7-(2-chloro-5-fluorophenyl)-N-methylisoquinolin-3-amine;

N-(7-(5-chloro-2-methoxyphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

7-(5-fluoro-2-methylphenyl)isoquinolin-3-amine;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclobutanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopentanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclohexanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)benzamide;

4-fluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)benzamide;

1-fluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-1-methylcyclopropanecarboxamide;

2-fluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

2,2-difluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2,5-dimethylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(6-aminopyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4-cyanopyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

2-fluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-cyano-5-fluoropyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(3-chloro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4-chloro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methoxyphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-isopropoxyphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(1-methyl-1H-pyrazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(3,5-dimethyl-1H-pyrazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-chloro-5-hydroxyphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4,5-difluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-4,4-dimethyl-4,5-dihydrooxazol-2-amine;

N-(7-(pyrrolidin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-cyclohexylisoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4-methylpiperazin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-cyclopentylisoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)tetrahydro-2H-pyran-4-carboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-1-methylpiperidine-4-carboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)isonicotinamide;

2-fluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)benzamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-4-methoxybenzamide;

N-(7-(3-methylpyridin-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(1H-indol-5-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4-hydroxypiperidin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(piperazin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(1-methyl-6-oxo-1,6-dihydropyridin-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)acetamide;

3,3,3-trifluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)propanamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)pivalamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-2-methoxyacetamide;

N-(7-(5-cyano-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-cyano-6-methoxyphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(pyridin-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1R,2R)-2-fluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

2-(dimethylamino)-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)acetamide;

1-ethyl-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-1H-pyrazole-5-carboxamide;

3-fluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)benzamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-2-methoxybenzamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-3-methoxybenzamide;

N-(7-(1H-indol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-cyano-4,5-difluorophenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-hydroxy-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)propionamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)isobutyramide;

N-(7-(pyrimidin-5-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4,6-dimethylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-methylthiazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(1H-pyrazol-5-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(1-methyl-4-oxo-1,4-dihydropyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

2,2,2-trifluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)acetamide;

N-(7-(2-cyano-5-fluorophenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-chloro-2-cyanophenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-cyano-4-fluorophenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

2,2-difluoro-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)acetamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)methanesulfonamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanesulfonamide;

1-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-3-methylurea;

N-(7-(phenylamino)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4-methylpyrimidin-5-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-methoxy-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-methyl-5-(trifluoromethyl)phenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-(dimethylamino)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(3-methylpyridin-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

3-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-1,1-dimethylurea;

N-(7-(2,4-dimethylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4,6-dimethylpyrimidin-5-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(1-methyl-1H-pyrazol-5-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoropyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-1-hydroxycyclopropanecarboxamide;

N-(7-(1H-pyrrol-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-cyano-5-hydroxyphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(3-hydroxy-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

7-(5-fluoro-2-methylphenyl)-N-(1,1,1-trifluoropropan-2-yl)isoquinolin-3-amine;

N-(cyclopropylmethyl)-7-(5-fluoro-2-methylphenyl)isoquinolin-3-amine;

4-chloro-7-(5-fluoro-2-methylphenyl)isoquinolin-3-amine;

N-(7-(4-fluoro-5-hydroxy-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-(hydroxymethyl)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4-fluoro-3-hydroxyphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylbenzamide;

1-ethyl-3-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)urea;

N-(4-chloro-7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

2-fluoro-N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4-methyl-1H-pyrazol-5-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(4-bromo-7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

1-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-3-(2-methoxyethyl)urea;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)piperidine-4-carboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-1-methylpyrrolidine-3-carboxamide;

1-ethyl-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)piperidine-4-carboxamide;

1-methyl-N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)piperidine-4-carboxamide;

N-(4-fluoro-7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

1-(4-chloro-7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-3-ethylurea;

1-ethyl-3-(4-fluoro-7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)urea;

2-cyclopropyl-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)acetamide;

(2-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-ylamino)pyridin-4-yl)methanol;

N-(7-(pyrazin-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-methylpyrazin-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

1-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-3-isopropylurea;

1-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-3-oxetan-3-yl)urea;

6-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-ylamino)pyridin-2(1H)-one;

N-(7-(5-fluoro-6-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-(2-hydroxypropan-2-yl)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

7-(5-fluoro-2-methylphenyl)-N-(6-methoxypyridin-2-yl)isoquinolin-3-amine;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-4-methylpiperazine-1-carboxamide;

N-(7-(2,5-dimethylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-methylpyridin-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

1-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-3-(tetrahydro-2H-pyran-4-yl)urea;

N-(7-(1H-indazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(1H-indazol-6-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(pyridazin-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(3-methylpyrazin-2-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide;

3-chloro-N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide;

isopropyl 7-(5-fluoro-2-methylphenyl)isoquinolin-3-ylcarbamate;

N-(7-(5-aminopyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-aminopyridin-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(6-chloro-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4-chloropyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(1-methyl-1H-indazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-oxoindolin-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-2-phenylcyclopropanecarboxamide;

(2-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-ylamino)-6-methylpyridin-4-yl)methanol;

2-(2-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-ylamino)-6-methylpyridin-4-yl)propan-2-ol;

N-(7-(6-amino-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(2-(7-(4-methylpyridin-3-yl)isoquinolin-3-ylamino)pyridin-4-yl)methanol;

N-(7-(5-(hydroxymethyl)-2-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-(1-hydroxyethyl)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(3-(hydroxymethyl)phenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-chloro-5-(hydroxymethyl)phenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-fluoro-5-(hydroxymethyl)phenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1S,2S)—N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-2-methylcyclopropanecarboxamide;

(1S,2R)—N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-2-methylcyclopropanecarboxamide;

(1R,2S)—N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-2-methylcyclopropanecarboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-1-methyl-1H-pyrazole-4-carboxamide;

N-(7-(2-(hydroxymethyl)pyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-2-methylisonicotinamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)tetrahydro-2H-pyran-4-carboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-3-(trifluoromethyl)benzamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-1-methylpiperidine-4-carboxamide;

(1R,2R)—N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)-2-methylcyclopropanecarboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-4-((dimethylamino)methyl)benzamide;

N-(7-(5-amino-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-hydroxy-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(6-(hydroxymethyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2-(hydroxymethyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(3-hydroxypyrrolidin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(3-(aminomethyl)phenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-(hydroxymethyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-4-(1-(dimethylamino)ethyl)benzamide;

(6-(7-(4-methylpyridin-3-yl)isoquinolin-3-ylamino)pyridin-2-yl)methanol;

N-(7-(4-(hydroxymethyl)pyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(4-chloro-3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)phenyl)tetrahydro-2H-pyran-4-carboxamide

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-fluorophenyl)tetrahydro-2H-pyran-4-carboxamide;

N-(6-o-tolylisoquinolin-3-yl)cyclopropanecarboxamide;

(R)—N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)tetrahydrofuran-2-carboxamide;

(S)—N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)tetrahydrofuran-2-carboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-fluorophenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide;

N-(4-chloro-3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)cyclobutanecarb(R)—N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)tetrahydrofuran-3-carboxamide;

(S)—N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)tetrahydrofuran-3-carboxamide;

N-(7-(6-(2-hydroxypropan-2-yl)-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

5-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-N,4-dimethylpicolinamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)morpholine-4-carboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-4-methylmorpholine-2-carboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)pyrrolidine-1-carboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-2-(hydroxymethyl)morpholine-4-carboxamide;

N-(7-(4-(trifluoromethyl)pyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-6-(hydroxymethyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(6-methoxy-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-4-(1-methylpyrrolidin-2-yl)benzamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-4-(1-methylpyrrolidin-3-yl)benzamide;

N-(7-(2-amino-4-methylpyrimidin-5-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(5-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylpyridin-3-yl)tetrahydro-2H-pyran-4-carboxamide;

7-(4-methylpyridin-3-yl)isoquinolin-3-amine;

(R)—N-(7-(6-(1-hydroxypropyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(S)—N-(7-(6-(1-hydroxypropyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(S)—N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-1,4-dioxane-2-carboxamide;

(R)—N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-1,4-dioxane-2-carboxamide;

N-(7-(5-amino-2-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(R)—N-(7-(6-(1-hydroxyethyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(S)—N-(7-(6-(1-hydroxyethyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(5-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-6-methylpyridin-3-yl)tetrahydro-2H-pyran-4-caN-(7-(5-methyl-1H-indazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-methyl-1H-pyrazolo[3,4-c]pyridin-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(3-(3-aminoisoquinolin-7-yl)-4-methylphenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide;

(1R,2R)-2-fluoro-N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)-3-oxabicyclo[3.1.0]hexane-6-carboxamide;

N-(7-(2-fluoro-5-methylpyridin-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(2,5-dimethylpyridin-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methyl-N-(tetrahydro-2H-pyran-4-yl)benzamide;

N-(7-(1H-pyrazolo[3,4-c]pyridin-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

2-(4-((dimethylamino)methyl)phenyl)-N-(7-(5-fluoro-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-(2-methoxyacetamido)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

(R)—N-(7-(5-(2-methoxypropanamido)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

(S)—N-(7-(5-(2-methoxypropanamido)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(1H-benzo[d]imidazol-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-(2-methoxy-2-methylpropanamido)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methyl-N-(oxetan-3-yl)benzamide;

N-(5-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-6-methylpyridin-3-yl)-4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)benzamide;

N-(7-(5-(ethylsulfonamido)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-1-hydroxycyclobutanecarboxamide;

N-cyclopropyl-7-(5-fluoro-2-methylphenyl)isoquinoline-3-carboxamide;

(S)—N-(7-(4-methyl-6-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(R)—N-(7-(4-methyl-6-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(4-methoxypyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-(cyclopentanesulfonamido)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)azetidine-1-carboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-1,1-dioxo-1-thiomorpholine-4-carboxamide;

(R)—N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-2-(hydroxymethyl)pyrrolidine-1-carboxamide;

(S)—N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-2-(hydroxymethyl)pyrrolidine-1-carboxamide;

(R)—N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-3-hydroxypyrrolidine-1-carboxamide;

(S)—N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylphenyl)-3-hydroxypyrrolidine-1-carboxamide;

N-(7-(2-(hydroxymethyl)-5-methylpyridin-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(5-hydroxy-2-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(R)-2,2-difluoro-N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(S)-2,2-difluoro-N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1S,2R)-2-fluoro-N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1R,2S)-2-fluoro-N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methyl-N-(1-methylcyclobutyl)benzamide;

3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methyl-N-(1,1-dioxo-3-methyltetrahydrothiophen-3-yl)benzamide;

N-cyclopentyl-3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylbenzamide;

(S)-3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methyl-N-(tetrahydrofuran-3-yl)benzamide;

(R)-3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methyl-N-(tetrahydrofuran-3-yl)benzamide;

3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-N-(2-methoxyethyl)-4-methylbenzamide;

3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-4-methylbenzamide;

3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methyl-N-(1-methyl-1H-pyrazol-4-yl)benzamide;

N-(7-(2-methyl-5-(morpholine-4-carbonyl)phenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(7-(3,5-dimethylpyridin-4-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

3-amino-7-(4-methylpyridin-3-yl)isoquinoline-4-carbonitrile;

N-(4-cyano-7-(4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

5-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methylpicolinic acid;

N-cyclobutyl-7-(5-fluoro-2-methylphenyl)isoquinoline-3-carboxamide;

N-(7-(6-(hydroxy(2H2)methyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-5-fluoro-4-methyl-N-(oxetan-3-yl)benzamide;

3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-2-fluoro-4-methyl-N-(oxetan-3-yl)benzamide;

3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-2-fluoro-4-methyl-N-(tetrahydro-2H-pyran-4-yl)benzamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-5-fluoro-4-methylphenyl)cyclobutanecarboxamide;

N-(7-(4-(2-hydroxyprop an-2-yl)-2-methylphenyl)isoquinolin-3-yl)cyclopropanecarboxamide;

N-(3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-2-fluoro-4-methylphenyl)cyclobutanecarboxamide;

3-(3-(cyclopropanecarboxamido)isoquinolin-7-yl)-4-methyl-N-(3-methyloxetan-3-yl)benzamide;

3-(3-((1S,2S)-2-fluorocyclopropanecarboxamido)isoquinolin-7-yl)-4-methyl-N-(3-methyloxetan-3-yl)benzamide;

2-fluoro-N-(7-(4-methyl-6-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(7-(4-methyl-6-((R)-2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

1-methyl-3-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)urea;

N-(7-(2-chloro-5-fluorophenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(5-chloro-7-(2-chlorophenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(2-chlorophenyl)-5-methyl-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(2-chlorophenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(2-chlorophenyl)-8-hydroxy-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

3-(2-chlorophenyl)-7-(cyclopropanecarboxamido)-2,6-naphthyridine 2-oxide;

N-(7-(2-chlorophenyl)-5-methoxy-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(2-chlorophenyl)-5-ethyl-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(2-chlorophenyl)-5-cyclopropyl-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-cyclohexyl-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(4-methylpyridin-3-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

7-(cyclopropanecarboxamido)-3-(5-fluoro-2-methylphenyl)-1-methyl-2,6-naphthyridine 2-oxide;

7-(cyclopropanecarboxamido)-3-(5-fluoro-2-methylphenyl)-2,6-naphthyridine 2-oxide;

N-(7-(5-fluoro-2-methylphenyl)-5-methyl-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(5-cyano-7-(5-fluoro-2-methylphenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(piperidin-1-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(5-(cyclopentyloxy)-7-(5-fluoro-2-methylphenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(hydroxymethyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-phenoxy-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(pyridin-3-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(phenylamino)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(5-(cyclopentylamino)-7-(5-fluoro-2-methylphenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(fluoromethyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(1-methyl-1H-pyrazol-5-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(methylsulfonyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-phenyl-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(5-(2,4-dimethylthiazol-5-yl)-7-(5-fluoro-2-methylphenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(4-methylpyridin-3-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(pyridin-4-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(1H-pyrazol-5-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(1-methyl-1H-pyrazol-4-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(1H-pyrazol-4-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(2-hydroxypropan-2-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-(hydroxymethyl)-2-methylphenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(piperidin-4-yloxy)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(5-((dimethylamino)methyl)-7-(5-fluoro-2-methylphenyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(piperazin-1-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-((methylamino)methyl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(pyrrolidin-3-yloxy)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

N-(7-(5-fluoro-2-methylphenyl)-5-(tetrahydrofuran-3-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(7-(4-methylpyridin-3-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(7-(5-methyl-1H-indazol-4-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

3-(7-((1S,2S)-2-fluorocyclopropanecarboxamido)-2,6-naphthyridin-3-yl)-4-methyl-N-(3-methyloxetan-3-yl)benzamide;

N-(2-(2,6-dichlorophenyl)-1,7-naphthyridin-6-yl)cyclopropanecarboxamide;

(3-(2-(2-chlorophenyl)-1,7-naphthyridin-6-ylamino)phenyl)methanol;

N-(2-(2-chlorophenyl)-1,7-naphthyridin-6-yl)cyclopropanecarboxamide;

N-(2-(2-chloro-5-fluorophenyl)-3-methyl-1,7-naphthyridin-6-yl)cyclopropanecarboxamide;

N-(2-(5-fluoro-2-methylphenyl)-4-methyl-1,7-naphthyridin-6-yl)cyclopropanecarboxamide;

N-(2-(1-hydroxycyclohexyl)-1,7-naphthyridin-6-yl)cyclopropanecarboxamide;

N-(2-(1-hydroxycyclopentyl)-1,7-naphthyridin-6-yl)cyclopropanecarboxamide;

Cyclopropanecarboxylic acid [7-(2-chloro-4-methyl-pyrimidin-5-yl)-isoquinolin-3-yl]-amide;

(R)—N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)oxetane-2-carboxamide;

(S)—N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)oxetane-2-carboxamide;

Cyclopropanecarboxylic acid [7-(2-chloro-4,6-difluoro-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(2-chloro-3,6-difluoro-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(2-fluoro-6-methyl-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(2-chloro-6-methyl-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(2,5-difluoro-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(2,6-difluoro-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(5-fluoro-2-methyl-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(5-chloro-2-methyl-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(3-chloro-pyridin-4-yl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid (7-pyridin-4-yl-isoquinolin-3-yl)-amide;

Cyclopropanecarboxylic acid (7-pyridin-3-yl-isoquinolin-3-yl)-amide;

Cyclopropanecarboxylic acid [7-(3-fluoro-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(3-chloro-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(2-chloro-5-fluoro-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(2,5-dichloro-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(2,6-dimethyl-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(2-chloro-6-trifluoromethyl-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(2-chloro-6-fluoro-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(2-cyano-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid (7-o-tolyl-isoquinolin-3-yl)-amide;

Cyclopropanecarboxylic acid [7-(2-chloro-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(2-fluoro-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid (7-phenyl-isoquinolin-3-yl)-amide;

Cyclopropanecarboxylic acid [7-(2,6-dichloro-phenyl)-isoquinolin-3-yl]-amide;

[7-(2,6-Dichloro-phenyl)-isoquinolin-3-yl]-[2-(4-methyl-piperazin-1-yl)-pyrimidin-4-yl]-amine;

[7-(2,6-Dichloro-phenyl)-isoquinolin-3-yl]-(2-morpholin-4-yl-pyrimidin-4-yl)-amine;

[7-(2,6-Dichloro-phenyl)-isoquinolin-3-yl]-(6-ethyl-2-morpholin-4-yl-pyrimidin-4-yl)-amine;

N-{7-[2,6-Difluoro-3-(propane-1-sulfonylamino)-phenyl]-isoquinolin-3-yl}-acetamide;

Cyclopropanecarboxylic acid [7-(3-fluoro-2-hydroxymethyl-6-methyl-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(5-fluoro-4-hydroxymethyl-2-methyl-phenyl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid {7-[5-fluoro-4-(1-hydroxy-1-methyl-ethyl)-2-methyl-phenyl]-isoquinolin-3-yl}-amide;

(1S,2S)—N-(7-(5-chloro-4-methyl-6-((R)-2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)isoquinolin-3-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)—N-(7-(5-chloro-4-methyl-6-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)isoquinolin-3-yl)-2-fluorocyclopropanecarboxamide;

2-Fluoro-cyclopropanecarboxylic acid [7-(4-methyl-pyridin-3-yl)-[2,6]naphthyridin-3-yl]-amide;

2-Fluoro-cyclopropanecarboxylic acid [7-(4-methyl-pyridin-3-yl)-[2,6]naphthyridin-3-yl]-amide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid [7-(5-fluoro-4-methyl-pyridin-3-yl)-5-methyl-[2,6]naphthyridin-3-yl]-amide;

2-Fluoro-cyclopropanecarboxylic acid [7-(2,4-dimethyl-azetidin-1-yl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(5-fluoro-4-methyl-pyridin-3-yl)-6-oxy-[2,6]naphthyridin-3-yl]-amide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid [7-(5-fluoro-4-methyl-pyridin-3-yl)-[2,6]naphthyridin-3-yl]-amide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid [7-(2-methoxy-4-methyl-pyridin-3-yl)-isoquinolin-3-yl]-amide;

(1R,2R)-2-Fluoro-cyclopropanecarboxylic acid [7-(4-methyl-pyridin-3-yl)-[2,6]naphthyridin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(1H-benzotriazol-4-yl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(6-fluoro-1H-indazol-4-yl)-isoquinolin-3-yl]-amide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid {7-[5-fluoro-6-(1-hydroxy-1-methyl-ethyl)-4-methyl-pyridin-3-yl]-isoquinolin-3-yl}-amide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid [7-(5-fluoro-4-methyl-pyridin-3-yl)-isoquinolin-3-yl]-amide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid [7-(5-fluoro-2-hydroxymethyl-4-methyl-pyridin-3-yl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(4-cyclopropyl-pyridin-3-yl)-isoquinolin-3-yl]-amide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid [7-(5-hydroxy-4-methyl-pyridin-3-yl)-isoquinolin-3-yl]-amide;

Cyclopropanecarboxylic acid [7-(3-methyl-1-oxy-pyridin-2-yl)-isoquinolin-3-yl]-amide;

2-Fluoro-cyclopropanecarboxylic acid [7-(6-methanesulfinyl-4-methyl-pyridin-3-yl)-isoquinolin-3-yl]-amide;

(1S,2S)—N-(7-(6-((R)-1-amino-2,2,2-trifluoroethyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)—N-(7-(6-((S)-1-amino-2,2,2-trifluoroethyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)-2-fluorocyclopropanecarboxamideyl}-amide;

(1R,2R)-2-ethoxy-N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1S,2S)-2-ethoxy-N-(7-(4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(7-(2-((R)-1-hydroxyethyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(7-(4-methyl-2-((R)-2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(7-(4-methyl-2-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(7-(2-((S)-1-hydroxyethyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(S)—N-(7-(4-methyl-6-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)isoquinolin-3-yl)isobutyramide;

(R)—N-(7-(4-methyl-6-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)isoquinolin-3-yl)isobutyramide;

(1S,2S)—N-(7-(6-(2,2-difluoro-1-hydroxyethyl)-4-methylpyridin-3-yl)isoquinolin-3-yl)-2-fluorocyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(7-((R)-2-methyl-5-oxopyrrolidin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(7-[((S)-2-methyl-5-oxopyrrolidin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide;

3-[3-(Cyclopropanecarbonyl-amino)-isoquinolin-7-yl]-N-(3,3-difluoro-cyclobutyl)-4-methyl-benz amide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid {7-[6-(1-hydroxy-1-methyl-ethyl)-4-methyl-pyridin-3-yl]-isoquinolin-3-yl}-amide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid {7-[6-(1-hydroxy-1-methyl-ethyl)-4-methyl-pyridin-3-yl]-[2,6]naphthyridin-3-yl}-amide;

(1S,2S)-2-fluoro-N-(7-(4-methyl-6-((S)-2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

(1S,2S)-2-fluoro-N-(7-(4-methyl-6-((R)-2,2,2-trifluoro-1-hydroxyethyl)pyridin-3-yl)-2,6-naphthyridin-3-yl)cyclopropanecarboxamide;

Cyclopropanecarboxylic acid [7-(4-methyl-1-oxy-pyridin-3-yl)-isoquinolin-3-yl]-amide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid [7-(4-methyl-pyridin-3-yl)-2-oxy-[2,6]naphthyridin-3-yl]-amide;

3-[3-(Cyclopropanecarbonyl-amino)-isoquinolin-7-yl]-N-(1-hydroxymethyl-cyclobutyl)-4-methyl-benzamide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid [7-(2-hydroxymethyl-4-methyl-pyridin-3-yl)-isoquinolin-3-yl]-amide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid [7-(2-trifluoromethoxy-phenyl)-[2,6]naphthyridin-3-yl]-amide;

(1S,2S)-2-Fluoro-cyclopropanecarboxylic acid [7-(5-methyl-1H-indazol-4-yl)-isoquinolin-3-yl]-amide;

N-Cyclobutyl-3-[3-(cyclopropanecarbo(1S,2S)—N-(7-(5-chloro-6-(2-hydroxypropan-2-yl)-4-methylpyridin-3-yl)isoquinolin-3-yl)-2-fluorocyclopropanecarboxamide;

3-(3-aminoisoquinolin-7-yl)-4-methyl-N-(1-methylcyclobutyl)benzamide;

3-(3-aminoisoquinolin-7-yl)-4-methyl-N-(3-methyloxetan-3-yl)benzamide;

5-(3-aminoisoquinolin-7-yl)-N-cyclobutyl-6-methylnicotinamide;

5-(3-aminoisoquinolin-7-yl)-6-methyl-N-(1-methylcyclobutyl)nicotinamide;

3-(3-aminoisoquinolin-7-yl)-2-fluoro-4-methyl-N-(3-methyloxetan-3-yl)benzamide and

3-(3-amino-4-chloroisoquinolin-7-yl)-4-methyl-N-(1-methylcyclobutyl)benzamidenyl-amino)-isoquinolin-7-yl]-4-methyl-benzamide.

24. A pharmaceutical composition comprising a compound in accordance with claim 1 and a pharmaceutically acceptable carrier, diluent or excipient.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 15, 2012
From: GENENTECH, INC.
To: F. HOFFMANN-LA ROCHE AG
Reel/Frame 028213/0016 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 11, 2012
From: LYSSIKATOS, JOSEPH P.; GAZZARD, LEWIS J.; HANAN, EMILY; KINTZ, SAMUEL; PURKEY, HANS EDWARD
To: GENENTECH, INC.
Reel/Frame 027519/0041 →
Continuity (2)
Provisional Application 61424567 · Dec 17, 2010
Related Publication 20120322785A1 · Dec 20, 2012