IP Library › Granted Patent US 12,516,059
Granted Patent B2
US 12,516,059 · App. 18/545,201 · Granted Jan 6, 2026

Pyrazolopyridine compounds and uses thereof

Inventors: Kai Liu (Chadds Ford, PA); Jun Pan (Media, PA); Alexander Sokolsky (Philadelphia, PA); Oleg Vechorkin (Wilmington, DE); Hai Fen Ye (Newark, DE); Qinda Ye (Claymont, DE); Wenqing Yao (Chadds Ford, PA)
Assignee: Incyte Corporation
C07D471/04C07D519/00
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Quick Facts
Patent No.
US 12,516,059
App. No.
18/545,201
Granted
Jan 6, 2026
Kind
B2
Abstract

Disclosed are compounds of Formula (I), methods of using the compounds for inhibiting HPK1 activity and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders associated with HPK1 activity such as cancer.

Claims (64)

1 . A compound selected from:

1-(3,5-Difluoro-4-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)phenyl)-N-methylmethanamine;

5-(2-Fluoro-6-methylphenyl)-3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

5-(2-Fluoro-6-methylphenyl)-3-(2-morpholinopyrimidin-5-yl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

3-(4-(4-Ethylpiperazin-1-yl)phenyl)-5-(2-fluoro-6-methylphenyl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

5-(6-Cyano-5-(2-fluoro-6-methylphenyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-N-methylpicolinamide;

5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(2-(4-methylpiperazin-1-yl)pyrimidin-5-yl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

3-(4-(4-Ethylpiperazin-1-yl)phenyl)-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(2-morpholinopyrimidin-5-yl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

5-(6-Cyano-5-(2-fluoro-6-methyl-4-((methylamino)methyl)phenyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-N-methylpicolinamide;

5-(2-Fluoro-6-methyl-4-((methylamino)methyl)phenyl)-3-(pyridin-3-yl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

5-(6-Fluoro-1,2,3,4-tetrahydroisoquinolin-5-yl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

3-(4-(4-Ethylpiperazin-1-yl)phenyl)-5-(6-fluoro-1,2,3,4-tetrahydroisoquinolin-5-yl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

5-(6-Fluoro-1,2,3,4-tetrahydroisoquinolin-5-yl)-3-(6-(4-methylpiperazin-1-yl)pyridin-3-yl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

5-(2-Fluoro-6-methylphenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-b]pyridine-6-carbonitrile;

3-(4-(4-Methylpiperazin-1-yl)phenyl)-5-phenyl-1H-pyrazolo[4,3-b]pyridine;

5-(2-Methoxyphenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridine;

3-(4-(4-Methylpiperazin-1-yl)phenyl)-5-o-tolyl-1H-pyrazolo[4,3-b]pyridine;

5-(2-Fluorophenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridine;

3-(4-(4-Methylpiperazin-1-yl)phenyl)-5-(2-(trifluoromethyl)phenyl)-1H-pyrazolo[4,3-pyridine;

2-Methyl-3-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)aniline;

5-(2-Fluoro-6-methylphenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-pyridine;

5-(2-Fluoro-6-methoxyphenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-pyridine;

5-(2,3-Difluorophenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridine;

5-(2,3-Difluoro-6-methoxyphenyl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-pyridine;

(3-Fluoro-2-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-enyl) methanol;

Ethyl 2-fluoro-3-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-bennzoate;

N-(2-Fluoro-3-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-enyl)methanesulfonamide;

2-(3-(4-(4-Methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)phenol;

5-(2,3-Dihydrobenzofuran-7-yl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-pyridine;

5-(2,3-Dihydrobenzo[b][1,4]dioxin-5-yl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridine;

N-Methyl-3-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-benzamide;

N,N-Dimethyl-3-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-iline;

2-(3-(4-(4-Methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)benzonitrile;

Methyl 2-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)benzoate;

N-(2-(3-(4-(4-Methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-enyl)acetamide;

5-(Biphenyl-2-yl)-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridine;

4-(3-(4-(4-Methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)indolin-2-one;

2-Fluoro-3-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)benzamide;

2-Fluoro-N-methyl-3-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-benzamide;

N-Benzyl-2-fluoro-3-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-benzamide;

2-Fluoro-3-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-N-(1-methylperidin-4-ylmethyl)benzamide;

5-(3-(4-(4-Methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-1,2,3,4-hydroisoquinoline;

4-(3-(4-(4-Methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-2,3-dihydro-1H-1-amine;

N-Methyl-4-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-2,3-dihydro-1H-inden-1-amine;

2-(4-(3-(4-(4-Methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-2,3-dihydro-1H-iden-1-ylamino) ethanol;

N-Benzyl-4-(3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrazolo[4,3-b]pyridin-5-yl)-2,3-dihydro-1H-inden-1-amine;

5-(2-Fluorophenyl)-3-phenyl-1H-pyrazolo[4,3-b]pyridine;

5-(2-Fluorophenyl)-3-(pyridin-4-yl)-1H-pyrazolo[4,3-b]pyridine;

4-(5-(2-Fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-N-methylbenzamide;

5-(2-Fluorophenyl)-3-(1-methyl-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-b]pyridine;

4-(5-(2-Fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-N-(1-methylpiperidin-4-benzamide;

(4-(5-(2-Fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)phenyl)(4-methylpiperazin-1-methanone;

4-(5-(2-Fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-N-phenylbenzamide;

5-(2-Fluorophenyl)-3-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo[4,3-b]pyridine;

5-(2-Fluorophenyl)-3-(1-(1-(methylsulfonyl)piperidin-4-yl)-1H-pyrazol-4-yl)-1H-pyrazolo 4,3-b]pyridine; and

1-(4-(4-(5-(2-Fluorophenyl)-1H-pyrazolo[4,3-b]pyridin-3-yl)-1H-pyrazol-1-yl)piperidin-1-ethanone;

or a pharmaceutically acceptable salt thereof.

2 . A pharmaceutical composition comprising a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient.

3 . A method of inhibiting HPK1 activity, said method comprising administering to a patient a compound of claim 1 , or a pharmaceutically acceptable salt thereof.

4 . A method for treating a cancer in a patient, said method comprising administering to the patient a therapeutically effective amount of the compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the cancer is selected from breast cancer, colorectal cancer, lung cancer, ovarian cancer, and pancreatic cancer.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 26, 2024
From: LIU, KAI; PAN, JUN; SOKOLSKY, ALEXANDER; VECHORKIN, OLEG; YE, HAI FEN; YE, QINDA; YAO, WENQING
To: INCYTE CORPORATION
Reel/Frame 067237/0215 →
Continuity (6)
Continuation 17558824 · Dec 22, 2021
Continuation 16786169 · Feb 10, 2020
Continuation 16454661 · Jun 27, 2019
Continuation 15698753 · Sep 8, 2017
Provisional Application 62385620 · Sep 9, 2016
Related Publication 20240383889A1 · Nov 21, 2024
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