IP Library › Granted Patent US 9,951,064
Granted Patent B2
US 9,951,064 · App. 15/152,947 · Granted Apr 24, 2018

Azaindazole compounds as inhibitors of T790M containing EGFR mutants

Inventors: Marian C. Bryan (San Francisco, CA); Bryan Chan (Foster City, CA); Francois Diederich (Basel, CH); Jennafer Dotson (Belmont, CA); Emily Hanan (Redwood City, CA); Timothy Heffron (Burlingame, CA); Michael Lainchbury (Harlow, GB); Robert Heald (Harlow, GB); Eileen M. Seward (Harlow, GB)
Assignee: GENENTECH, INC.
C07D471/04A61K31/506A61K31/517A61K31/5377A61K31/5386A61K31/541A61K45/06C07D519/00
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Quick Facts
Patent No.
US 9,951,064
App. No.
15/152,947
Granted
Apr 24, 2018
Kind
B2
Abstract

This invention relates to novel compounds which are inhibitors of T790M containing EGFR mutants, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the prevention or treatment of cancer.

Claims (232)

1. A compound of Formula (I)

wherein,

R1 is C 3 -C 7 heterocycloalkyl, heteroaryl, —O(C 1 -C 6 alkyl), or —NR a R b , wherein said C 3 -C 7 heterocycloalkyl and heteroaryl may be further substituted with one to five R f groups;

R2 is hydrogen, C 3 -C 7 cycloalkyl, C 3 -C 7 heterocycloalkyl or unsubstituted C 1 -C 6 alkyl;

R3 is C 1 -C 6 alkyl, C 3 -C 7 heterocycloalkyl, C 3 -C 7 cycloalkyl, —O(C 1 -C 6 alkyl), CN, —NR a R b , —NHC(O)(C 1 -C 3 alkyl), —C(O)NR a R b , or heteroaryl;

wherein each R f is independently selected from the group consisting of C 1 -C 3 alkyl, alkoxy, amino, hydroxy, alkylamino, amide, urea, oxo, halo, pyrazolyl, imidazolyl, triazolyl, CN, —NHC(O)(C 1 -C 3 alkyl), acyl, sulfonyl, sulfoxide, sulfonamide, sulfoximinyl, —(CH 2 ) m C 3 -C 7 heterocycloalkyl, —O(C 1 -C 6 alkyl), —C(O)OR a ;

wherein each R a is independently H or C 1 -C 6 alkyl, each R b is independently H, C 1 -C 6 alkyl, alkoxy, amino, —(CH 2 ) m C(O)NH 2 , —(CH 2 ) m C 3 -C 7 cycloalkyl, —(CH 2 ) m C 3 -C 7 heterocycloalkyl or —(CH 2 ) m heteroaryl, or R a and R b together may form a C 3 -C 7 cycloalkyl, C 3 -C 7 heterocycloalkyl or heteroaryl ring, wherein said C 3 -C 7 cycloalkyl, C 3 -C 7 heterocycloalkyl and heteroaryl may each be further substituted with one to three groups selected from the group consisting of halo, hydroxy, C 1 -C 3 alkyl, amino, oxo, amide, sulfonyl, sulfoxide, sulfoximinyl, sulfonamide, alkoxy, CN and acyl; each m is independently 0, 1, 2 or 3;

or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , wherein R1 is C 3 -C 7 heterocycloalkyl; or a pharmaceutically acceptable salt thereof.

3. A compound according to claim 1 , wherein R1 is heteroaryl; or a pharmaceutically acceptable salt thereof.

4. A compound according to claim 1 , wherein R1 is —NR a R b ; or a pharmaceutically acceptable salt thereof.

5. A compound of claim 1 , wherein R1 is heteroaryl or C 3 -C 7 heterocycloalkyl, R f is sulfonyl or alkoxy, R3 is —NR a R b or heteroaryl, R2 is C 1 -C 6 alkyl, or a pharmaceutically acceptable salt thereof.

6. A compound of claim 5 , wherein R1 is piperdinyl or pyrazolyl, or a pharmaceutically acceptable salt thereof.

7. A compound of claim 1 , wherein R f is —SO 2 (cyclopropyl), halo, hydroxy, C 1 -C 6 alkyl or methoxy, or a pharmaceutically acceptable salt thereof.

8. A compound according to claim 1 , wherein R2 is unsubstituted C 1 -C 6 alkyl.

9. A compound according to claim 8 , wherein R3 is C 1 -C 3 alkyl, C 3 -C 7 heterocycloalkyl, heteroaryl, —NR a R b or —C(O)NR a R b ; or a pharmaceutically acceptable salt thereof.

10. A compound according to claim 1 , wherein R1 is a C 3 -C 7 heterocycloalkyl or heteroaryl selected from the group consisting of piperidinyl and pyrazolyl, wherein said C 3 -C 7 heterocycloalkyl or heteroaryl may be further substituted with one to three R f groups selected from C 1 -C 6 alkyl, alkoxy, hydroxyl, halo, sulfonyl, and sulfonamide; or a pharmaceutically acceptable salt thereof.

11. A compound according claim 1 , wherein R2 is isopropyl or sec-butyl; or a pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

13. A method of treating cancer comprising administering to a human in need thereof an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof in a pharmaceutical composition.

14. A method of claim 13 , wherein said cancer is non-small cell lunch cancer.

15. A compound, selected from the group consisting of:

4-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)thiomorpholine 1,1-dioxide;

1-Isopropyl-N-(2-(4-methoxypiperdin-1-yl)pyrimidin-4-yl)-3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrazolo[4,3-c]pyridine-6-amine;

1-(4-((1-Isopropyl-3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-3,3-dimethylpiperidin-4-ol;

N-(2-(1-(Cyclopropylmethyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-amine

N-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-amine;

2-((6-((2-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)amino)ethanol;

N-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-3-fluoro-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-amine;

1-(4-((1-Isopropyl-3-(pyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino) pyrimidin-2-yl)-3,3-dimethylpiperidin-4-ol;

N-(2-(1-((Cyclopropylmethyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-3-morpholino-1H-pyrazolo[4,3-c]pyridin-6-amine;

1-(4-((1-Isopropyl-3-(4-methyl-1H-pyrazol-5-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-3,3-dimethylpiperidin-4-ol;

1-Isopropyl-6-((2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridine-3-carboxamide;

1-(4-((1-(sec-Butyl)-3-(3-(2-hydroxypropan-2-yl)azetidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-3,3-dimethylpiperidin-4-ol;

2-(1-(1-(sec-Butyl)-6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)propan-2-ol;

1-Isopropyl-N-(2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)-3-(pyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-amine;

N 6 -(2-(1-(Ethylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-N 3 -(oxetan-3-yl)-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

1-(6-(2-(1-(Ethylsulfonyl)-1H-pyrazol-4-yl) pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c] pyridin-3-yl)-N,N-dimethylazetidine-3-carboxamide;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl) pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c] pyridin-3-yl) pyrrolidin-3-ol;

N-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl) pyrimidin-4-yl)-1-isopropyl-3-(tetrahydrofuran-3-yl)-1H-pyrazolo [4,3-c] pyridin-6-amine;

(±)-cis-3-Fluoro-1-[4-(1-isopropyl-3-morpholin-4-yl-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl]piperidin-4-ol;

(±)-cis-3-Fluoro-1-{4-[1-isopropyl-3-(2-oxa-6-azaspiro[3.3]hept-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino]-pyrimidin-2-yl}piperidin-4-ol;

(±)-1-(6-((2-(cis-3-Fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)imidazolidin-2-one;

(±)-2-(cis-3-Fluoro-4-methoxypiperidin-1-yl)pyrimidin-4-yl]-[1-isopropyl-3-(2-oxa-6-azaspiro[3.3]hept-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]amine;

1-(4-(Aminocyclohexyl)methyl)-N 6 -[2-(4-methoxypiperidin-1-yl)-pyrimidin-4-yl]-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

1-(1-(sec-Butyl)-6-((2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)imidazolidin-2-one;

(±)-1-(1-(sec-Butyl)-6-((2-(cis-3-fluoro-4-methoxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)imidazolidin-2-on;

1-(sec-Butyl)-N-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-3-morpholino-1H-pyrazolo[4,3-c]pyridin-6-amine;

(R)-1-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidine-3-carbonitrile;

N-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-3-(tetrahydrofuran-3-yloxy)-1H-pyrazolo[4,3-c]pyridin-6-amine;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-N-(2-methoxyethyl)azetidine-3-carboxamide;

N-(2-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-3-(pyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-amine;

N-(2-(1-(cyclopropylmethyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-amine;

1-(4-((1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-3,3-dimethylpiperidin-4-ol;

1-(4-((1-isopropyl-3-morpholino-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-3,3-dimethylpiperidin-4-ol;

N6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-N3-(oxetan-3-yl)-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

(1-(6-(2-(1-(ethylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)methanol;

1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-ol;

N6-(2-(1-(ethylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-N3-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

(S)—N6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-N3-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

(R)—N6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-N3-(tetrahydrofuran-3-yl)-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

(R)-(1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidin-3-yl)methanol;

1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-trans-4-fluoropyrrolidin-3-ol;

1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-4,5-dihydro-1H-imidazol-2-ol;

1-isopropyl-N6-(2-(4-methoxypiperidin-1-yl)pyrimidin-4-yl)-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

N6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

N6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-N3,1-diisopropyl-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

3-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-ylamino)propanamide;

2-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-ylamino)acetamide;

3-((6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)(methyl)amino)propane-1,2-diol;

N-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1,3-diisopropyl-1H-pyrazolo[4,3-c]pyridin-6-amine;

N-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-3-morpholino-1H-pyrazolo[4,3-c]pyridin-6-amine;

N6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-N3-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

(4-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)morpholin-2-yl)methanol;

3-(azetidin-1-yl)-N-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-amine;

1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidine-3-carboxamide;

1-(6-(2-(4-hydroxy-3,3-dimethylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-N,N-dimethylazetidine-3-carboxamide;

1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-N,N-dimethylazetidine-3-carboxamide;

(S)-(1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidin-3-yl)methanol;

4-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-2-one;

1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidine-3-carboxamide;

1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-ylamino)-2-methylpropan-2-ol;

N-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-3-isopropoxy-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-amine;

(1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)methanol;

(3RS,4SR)-3-Fluoro-1-{4-[1-isopropyl-3-(2-oxa-6-azaspiro[3.3]hept-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino]pyrimidin-2-yl)}-4-methylpiperidin-4-ol;

(3R*,4S*)-1-{4-[1-((S)-sec-Butyl)-3-(2-oxa-6-azaspiro[3.3]hept-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino]pyrimidin-2-yl}-3-fluoro-4-methylpiperidin-4-ol;

(3R*,4S*)-1-{4-[1-((S)-sec-Butyl)-3-(2-oxa-6-azaspiro[3.3]hept-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino]pyrimidin-2-yl}-3-fluoro-4-methylpiperidin-4-ol;

(3R*,4S*)-1-{4-[1-((S)-sec-Butyl)-3-(2-oxa-6-azaspiro[3.3]hept-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino]pyrimidin-2-yl}-3-fluoro-4-methylpiperidin-4-ol;

(3R*,4S*)-1-{4-[1-((R)-sec-Butyl)-3-(2-oxa-6-azaspiro[3.3]hept-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino]pyrimidin-2-yl}-3-fluoro-4-methylpiperidin-4-ol;

(3R*,4S*)-1-{4-[1-((R)-sec-Butyl)-3-(2-oxa-6-azaspiro[3.3]hept-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino]pyrimidin-2-yl}-3-fluoro-4-methylpiperidin-4-ol;

(3R*,4S*)-1-{4-[1-((S)-sec-Butyl)-3-((R)-3-hydroxypyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino]pyrimidin-2-yl}-3-fluoro-4-methylpiperidin-4-ol;

(3R*,4S*)-1-{4-[1-((S)-sec-Butyl)-3-((S)-3-hydroxypyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino]pyrimidin-2-yl}-3-fluoro-4-methylpiperidin-4-ol;

[1-((S)-sec-Butyl)-3-(2-oxa-6-azaspiro[3.3]hept-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-[2-(2-methanesulfonyl-2-methylpropoxy)pyrimidin-4-yl]amine;

3-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)oxazolidin-2-one;

3-(8-Oxa-3-azabicyclo[3.2.1]octan-3-yl)-N-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-amine;

N 3 -tert-Butyl-N 6 -(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

cis-3-Fluoro-1-(4-(3-((R)-2-(hydroxymethyl)morpholino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)piperidin-4-ol;

1-(6-(2-(cis-3-Fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-3-methylimidazolidin-2-one;

4-(6-(2-(4-Hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-ylamino)pyrrolidin-2-one;

2-Hydroxy-1-(4-(6-(2-(4-hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)-2-methylpropan-1-one;

(3RS, 4SR)-3-Fluoro-1-(4-(3-((R)-3-hydroxypyrrolidin-1-yl)-1-((S*)-1,1,1-trifluoropropan-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

(±)-1-(4-(1-sec-Butyl-3-(3-hydroxy-3-(hydroxymethyl)azetidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

2-(1-(4-(1-sec-Butyl-3-((R)-3-hydroxypyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-4-methoxypiperidin-4-yl)acetonitrile;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-3-methylazetidin-3-ol;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-3-methylimidazolidin-2-one;

2-(1-(6-(2-(4-Hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)-2-methylpropanamide;

1-(4-(3-(3,3-Difluoro-4-hydroxypyrrolidin-1-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

4-Amino-1-(6-(2-(4-hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidin-2-one;

4-Methyl-1-[4-[(3-[2-oxa-6-azaspiro[3.3]heptan-6-yl]-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino]pyrimidin-2-yl]piperidin-4-ol;

(±)-1-(6-(2-(cis-3-Fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-4,4-dimethylimidazolidin-2-one;

4-[1-(sec-Butyl)-6-[[2-(4-hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-yl]amino]-1H-pyrazolo[4,3-c]pyridin-3-yl]-1-imino-4-thiomorpholin-1-one;

1-(1-sec-Butyl-6-(2-(cis-5-fluoro-4-hydroxy-3,3-dimethylpiperidin-1-yl)pyrimidin-4-ylamino)-1H-pyrazolo[4,3-c]pyridine-3-yl)imidazolidin-2-one;

N-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-3-(2,5-dimethylpyrrolidin-1-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-amine;

4-(1-sec-Butyl-6-(2-(4-hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-2-one;

6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridine-3-carbonitrile;

1-(4-(1-Isopropyl-3-(2-methyltetrahydrofuran-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

4-(6-(2-(4-Hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyrindin-3-yl)-2,2-dimethyl-1,2-dihydroimidazol-5-one;

[1-((R)-sec-Butyl)-3-(2-oxa-6-azaspiro[3.3]hept-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-[2-(2-methanesulfonyl-2-methylpropoxy)pyrimidin-4-yl]amine;

[1-(sec-Butyl)-3-(2-oxa-6-azaspiro[3.3]hept-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-[2-(2-methanesulfonyl-2-methylpropoxy)pyrimidin-4-yl]amine;

1-{1-(sec-Butyl)-6-[2-((3R,4S)-3-fluoro-4-methoxypiperidin-1-yl)pyrimidin-4-ylamino]-1H-pyrazolo[4,3-c]pyridin-3-yl}imidazolidin-2-one;

1-{1-sec-Butyl-6-[2-(2-methanesulfonyl-2-methylpropoxy)pyrimidin-4-ylamino]-1H-pyrazolo[4,3-c]pyridin-3-yl}imidazolidin-2-one;

N4 (1-Isopropyl-3-morpholin-4-yl-1H-pyrazolo[4,3-c]pyridin-6-yl)-N2-(2-methanesulfonyl-2-methylpropyl)pyrimidine-2,4-diamine;

1-{1-sec-Butyl-6-[2-(2-methanesulfonyl-2-methylpropylamino)pyrimidin-4-ylamino]-1H-pyrazolo[4,3-c]pyridin-3-yl}imidazolidin-2-one;

1-{1-sec-Butyl-6-[2-(4-methanesulfonylpiperidin-1-yl)pyrimidin-4-ylamino]-1H-pyrazolo[4,3-c]pyridin-3-yl}imidazolidin-2-one;

[2-((cis)-(±)-3-Fluoro-4-methoxypiperidin-1-yl)pyrimidin-4-yl]-[1-isopropyl-3-(2-oxa-6-azaspiro[3.3]hept-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl]amine;

(3S*,4R*)-3-fluoro-1-(4-((3-(3-hydroxy-3-methylpyrrolidin-1-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)piperidin-4-ol;

(3S*,4R*)-3-fluoro-1-(4-((3-((R)-3-hydroxypyrrolidin-1-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)piperidin-4-ol;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidin-2-one;

3-((6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)amino)tetrahydrothiophene 1,1-dioxide;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-4-methylimidazolidin-2-one;

2-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-ylamino)propanamide;

4-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)thiomorpholine 1-oxide;

4-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-1-iminothiomorpholine 1-oxide;

7-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-2,7-diazaspiro[4.4]nonan-1-one;

1-(1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)ethanol;

(R)-1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidin-3-ol;

7-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-2,7-diazaspiro[4.4]nonan-3-one;

N-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-2-hydroxy-2-methylpropanamide;

N-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-3-(3-morpholinoazetidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-amine;

N-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-3-(4-ethylpiperazin-1-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-amine;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperidin-4-ol;

N-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-3-(2-oxa-6-azaspiro[3.4]octan-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-amine;

2-(1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)acetonitrile;

(1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-3-methylazetidin-3-yl)methanol;

(S)-1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidin-3-ol;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-3-(hydroxymethyl)azetidin-3-ol;

N6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-N3-(2-(S-methylsulfonimidoyl)ethyl)-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

N-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-3-(6-(2,2,2-trifluoroethyl)-2,6-diazaspiro[3.3]heptan-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-amine;

1-(6-(2-(cis-3-Fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridine-3-yl)-4-methylimidazolidin-2-one;

1-(6-(2-(cis-3-Fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-5-methylimidazolidin-2-one;

(±)cis-3-Fluoro-1-(4-(3-(3-hydroxy-3-(trifluoromethyl)azetidin-1-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)piperidin-4-ol;

(±)-cis-3-Fluoro-1-(4-(3-(3-fluoro-3-(hydroxymethyl)azetidin-1-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)piperidin-4-ol;

cis-3-Fluoro-1-(4-(3-(trans-3-fluoro-4-hydroxypyrrolidin-1-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)piperidin-4-ol;

cis-3-Fluoro-1-(4-(3-((S)-2-(hydroxymethyl)morpholino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)piperidin-4-ol;

(±)-1 (6-(2-(cis-3-Fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidin-2-one;

1-(4-(6-(2-(4-Hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)propan-1-one;

2-Hydroxy-1-(4-(6-(2-(4-hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)ethanone;

2-Hydroxy-1-(4-(6-(2-(4-hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)propan-1-one;

1-(6-(2-(4-Hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-5-oxopyrrolidine-3-carbonitrile;

6-(6-((2-(4-Hydroxy-1-methylpiperidin-1-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-2-thia-6-azaspiro[3.3]heptane 2-oxide;

1-(4-(3-(2-(5-Amino-1,3-dioxan-2-yl)ethylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

(3RS,4SR)-3-Fluoro-1-(4-(3-((R)-3-hydroxypyrrolidin-1-yl)-1-((R*)-1,1,1-trifluoropropan-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

(±)-cis-3-Fluoro-1-(4-(3-((R)-3-hydroxypyrrolidin-1-yl)-1-((S*)-1,1,1-trifluoropropan-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)piperidin-4-ol;

(±)-cis-3-Fluoro-1-(4-(3-((R)-3-hydroxypyrrolidin-1-yl)-1-((R*) 1,1,1-trifluoropropan-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)piperidin-4-ol;

1-(4-(3-((R)-3-Hydroxypyrrolidin-1-yl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

(3S)-1-(1-sec-Butyl-6-(2-(4-hydroxy-4-methylpiperidin-1l-yl)pyrimidin-4-ylamino)-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidine-3-carboxamide;

(3R)-1-(1-sec-Butyl-6-(2-(4-hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidine-3-carboxamide;

1-(4-(1-sec-Butyl-3-(3,3-difluoroazetidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

(4SR,5RS)-1-(4-((1-(sec-Butyl)-3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-5-fluoro-3,3-dimethylpiperidin-4-ol;

cis-5-Fluoro-1-(4-(3-((R)-3-hydroxypyrrolidin-1-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-3,3-dimethylpiperidin-4-ol;

2-(1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyrindin-3-yl)azetidin-3-yl)propan-2-ol;

3-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-tetrahydropyrimidin-2(1H)-one;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-3-ethylimidazolidin-2-one;

N-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-3-(3-(methoxymethyl)azetidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-amine;

2-(1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)-2-methylpropanenitrile;

N-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-3-(3,3-difluoroazetidin-1-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-amine;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidine-3-carbonitrile;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-N,N-dimethylpyrrolidine-3-carboxamide;

1-(6-(2-(4-Hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-3-methylpyrrolidine-3-carboxamide;

(R)-3-Amino-1-(6-(2-(4-hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidin-2-one;

(S)-3-Amino-1-(6-(2-(4-hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidin-2-one;

6-(6-((2-(4-Hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-2-thia-6-azaspiro[3.3]heptane 2,2-dioxide;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-N-methylazetidine-3-carboxamide;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-N-methylazetidine-3-carboxamide;

(1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)(morpholino)methanone;

(R)-(1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)(3-hydroxypyrrolidin-1-yl)methanone;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-N-(2,2,2-trifluoroethyl)azetidine-3-carboxamide;

(S)-(1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)(3-(hydroxymethyl)pyrrolidin-1-yl)methanone;

(R)-(1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)(3-(hydroxymethyl)pyrrolidin-1-yl)methanone;

8-Oxa-3-azabicyclo[3.2.1]octan-3-yl(1-(6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)methanone;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-N-isopropylazetidine-3-carboxamide;

1-(6-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-N-(3-hydroxycyclobutyl)azetidine-3-carboxamide;

1-(6-(2-(4-Hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazolo[4,3-c]pyridin-3-yl)imidazolidin-2-one;

N-(2-(1-Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1-(1,1,1-trifluoropropan-2-yl)-1H-pyrazolo[4,3-c]pyridin-6-amine;

(±)-1-(6-(2-(cis)-3-Fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-4-hydroxypyrrolidin-2-one;

(±)-cis-1-(4-(3-(3,3-Difluoroazetidin-1-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-3-fluoropiperidin-4-ol;

(±)-2-(6-((2-((cis)-3-Fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-2-azaspiro[3.3]heptan-6-ol;

(4S)-1-(1-sec-Butyl-6-(2-(4-hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1H-pyrazolo[4,3-c]pyridin-3-yl)-4-(hydroxymethyl)imidazolidin-2-one;

1-(4-(3-(cis-3-Amino-4-fluoropyrrolidin-1-yl)-1-sec-butyl-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

1-(4-(1-sec-Butyl-3-(trans-3-fluoro-4-hydroxypyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

2-(6-(2-(cis-3-Fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-ylamino)propanenitrile;

N-(2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-3-(3,5-dimethylmorpholino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-amine;

N6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)-1-isopropyl-N3-(2,2,2-trifluoroethyl)-1H-pyrazolo[4,3-c]pyridine-3,6-diamine;

(±)-2-(6-(2-(cis-3-Fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-ylamino)-2-methylpropanamide;

(±)-2-(6-(2-(cis-3-Fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-ylamino)-2-methylpropanenitrile;

1-(4-(3-(4-Amino-3,3-difluoropyrrolidin-1-yl)-1-sec-butyl-1H-pyrazolo[4,3-c]pyridin-6-ylamino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

(3S)-1-(1-sec-Butyl-6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1H-pyrazolo[4,3-c]pyridin-3-yl)-3-hydroxypyrrolidin-2-one;

(3R)-1-(1-sec-Butyl-6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1H-pyrazolo[4,3-c]pyridin-3-yl)-3-hydroxypyrrolidin-2-one;

(2S)-1-(4-(1-sec-Butyl-6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)-2-hydroxypropan-1-one;

(2R)-1-(4-(1-sec-Butyl-6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1H-pyrazolo[4,3-c]pyridin-3-yl)piperazin-1-yl)-2-hydroxypropan-1-one;

(4S)-1-(1-sec-Butyl-6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1H-pyrazolo[4,3-c]pyridin-3-yl)-4-(hydroxymethyl)imidazolidin-2-one;

1-(1-(1-sec-Butyl-6-(2-(1-(cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-ylamino)-1H-pyrazolo[4,3-c]pyridin-3-yl)azetidin-3-yl)ethanol;

(±)-1-(6-(2-(4-Hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidine-cis-3,4-diol;

(3S,4S)-1-(6-(2-(4-Hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-ylamino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidine-3,4-diol;

(3S,4R)-1-((1-((R*)-sec-Butyl)-3-(3-(2-hydroxypropan-2-yl)azetidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-3-fluoropiperidin-4-ol;

(3S,4R)-1-((1-((S*)-sec-Butyl)-3-(3-(2-hydroxypropan-2-yl)azetidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-3-fluoropiperidin-4-ol;

1-(1-(sec-Butyl)-6-((2-((3R,4S)-3-fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)imidazolidin-2-one;

(3R,4S)-1-(4-((1-(sec-Butyl)-3-((R)-3-hydroxypyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-3-fluoropiperidin-4-ol;

(3S,4R)-1-(4-((1-((R*)-sec-Butyl)-3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-3-fluoropiperidin-4-ol;

(3S,4R)-1-(4-((1-((S*)-sec-Butyl)-3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-3-fluoropiperidin-4-ol;

(S)-1-(6-((2-(1-(Cyclopropylsulfonyl)-1H-pyrazol-4-yl)pyrimidin-4-yl)amino)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-3-yl)-3-hydroxypyrrolidin-2-one;

1-(1-(sec-Butyl)-6-((2-((3S,4R)-3-fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidin-2-one;

(3S)-1-(1-(sec-Butyl)-6-((2-((3S,4R)-3-fluoro-4-hydroxypiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)-3-hydroxypyrrolidin-2-one;

1-(4-((1-(sec-Butyl)-3-(2-oxa-6-azaspiro[3.3]heptan-6-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

1-(4-((1-(sec-Butyl)-3-((R)-3-hydroxypyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

1-(1-(sec-Butyl)-6-((2-(4-hydroxy-4-methylpiperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidin-2-one;

(R)-1-(4-((3-(3-Hydroxypyrrolidin-1-yl)-1-isopropyl-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-4-methylpiperidin-4-ol;

(3R)-1-(1-(sec-Butyl)-6-((2-(4-(methyl sulfonyl)piperidin-1-yl)pyrimidin-4-yl)amino)-1H-pyrazolo[4,3-c]pyridin-3-yl)pyrrolidin-3-ol;

9-(4-((1-((S*)-sec-Butyl)-3-((R)-3-hydroxypyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;

9-(4-((1-((R*)-sec-Butyl)-3-((R)-3-hydroxypyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-1-oxa-4,9-diazaspiro[5.5]undecan-3-one;

(S*)-1-(4-((1-((S*)-sec-Butyl)-3-((R)-3-hydroxypyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-3-methylpyrrolidine-3-carboxamide; and

(S*)-1-(4-((1-((R*)-sec-Butyl)-3-((R)-3-hydroxypyrrolidin-1-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)amino)pyrimidin-2-yl)-3-methylpyrrolidine-3-carboxamide.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 8, 2016
From: BRYAN, MARIAN C.; CHAN, BRYAN; DIEDERICH, FRANCOIS; DOTSON, JENNAFER; HANAN, EMILY; HEFFRON, TIMOTHY
To: GENENTECH, INC.
Reel/Frame 039107/0887 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 8, 2016
From: LAINCHBURY, MICHAEL; HEALD, ROBERT; SEWARD, EILEEN M.
To: ARGENTA DISCOVERY 2009 LIMITED
Reel/Frame 039108/0205 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 8, 2016
From: ARGENTA DISCOVERY 2009 LIMITED
To: GENENTECH, INC.
Reel/Frame 039108/0315 →
Continuity (4)
Continuation PCTUS2014044401 · Jun 26, 2014
Provisional Application 61950497 · Mar 10, 2014
Provisional Application 61840716 · Jun 28, 2013
Related Publication 20160257682A1 · Sep 8, 2016