IP Library › Granted Patent US 12,194,051
Granted Patent B2
US 12,194,051 · App. 17/288,164 · Granted Jan 14, 2025

5-azaindazole derivatives as adenosine receptor antagonists

Inventors: Anne-Laure Blayo (Credin, FR); Baptiste Manteau (Ways, BE); Camille Amalric (Strassbourg, FR); Stanislas Mayer (Eschau, FR); Stephan Schann (Illkirch, FR); Mickaël Fer (Ostwald, FR)
Assignee: MERCK PATENT GMBH
A61K31/553A61K31/4545A61K31/46A61K31/497A61K31/506A61K31/5386A61P35/00C07D471/04C07D519/00C07B2200/05
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Quick Facts
Patent No.
US 12,194,051
App. No.
17/288,164
Granted
Jan 14, 2025
Kind
B2
Abstract

The present invention relates to novel 5-azaindazole derivatives of formula (I), as described and defined herein, and pharmaceutically acceptable salts, solvates and prodrug thereof, as well as pharmaceutical compositions comprising such compounds. The 5-azaindazole derivatives according to the invention have been found to be highly effective dual A 2A /A 2B adenosine receptor antagonists, and can thus be used as therapeutic agents, particularly in the treatment or prevention of hyperproliferative or infectious diseases or disorders.

Claims (410)

1. A compound of formula (I)

wherein:

R 1A and R 1B are mutually linked to form, together with the nitrogen atom that they are attached to, a group which is selected from

wherein each one of the above-depicted groups is optionally substituted with one or more groups R 11 ;

each R 11 is independently selected from C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —(C 0-3 alkylene)-OH, —(C 0-3 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-O(C 1-5 alkylene)-OH, (C 0-3 alkylene)-O(C 1-5 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-SH, —(C 0-3 alkylene)-S(C 1-5 alkyl), —(C 0-3 alkylene)-NH 2 , —(C 0-3 alkylene)-NH(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-halogen, —(C 0-3 alkylene)-(C 1-5 haloalkyl), —(C 0-3 alkylene)-O—(C 1-5 haloalkyl), —(C 0-3 alkylene)-CF 3 , —(C 0-3 alkylene)-CN, —(C 0-3 alkylene)-NO 2 , —(C 0-3 alkylene)-CHO, —(C 0-3 alkylene)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-COOH, —(C 0-3 alkylene)-CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-CO—NH 2 , —(C 0-3 alkylene)-CO—NH(C 1-5 alkyl), —(C 0-3 alkylene)-CO—N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —NH 2 , —(C 0-3 alkylene)-SO 2 —NH(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-SO—(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-carbocyclyl, and —(C 0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety of said —(C 0-3 alkylene)-carbocyclyl and the heterocyclyl moiety of said —(C 0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —OH, —O(C 1-5 alkyl), —O(C 1-5 alkylene)-OH, —O(C 1-5 alkylene)-O(C 1-5 alkyl), —SH, —S(C 1-5 alkyl), —NH 2 , —NH(C 1-5 alkyl), —N(C 1-5 alkyl)(C 1-5 alkyl), halogen, C 1-5 haloalkyl, —O—(C 1-5 haloalkyl), —CF 3 , —CN, —NO 2 , —CHO, —CO—(C 1-5 alkyl), —COOH, —CO—O—(C 1-5 alkyl), —O—CO—(C 1-5 alkyl), —CO—NH 2 , —CO—NH(C 1-5 alkyl), —CO—N(C 1-5 alkyl)(C 1-5 alkyl), —NH—CO—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —SO 2 —NH 2 , —SO 2 —NH(C 1-5 alkyl), —SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —NH—SO 2 —(C 1-5 alkyl), —N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —SO—(C 1-5 alkyl), —SO 2 —(C 1-5 alkyl), cycloalkyl, and heterocycloalkyl;

R 2 and R 4 are each independently selected from hydrogen, C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —(C 0-3 alkylene)-OH, —(C 0-3 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-O(C 1-5 alkylene)-OH, —(C 0-3 alkylene)-O(C 1-5 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-SH, —(C 0-3 alkylene)-S(C 1-5 alkyl), —(C 0-3 alkylene)-NH 2 , —(C 0-3 alkylene)-NH(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-halogen, —(C 0-3 alkylene)-(C 1-5 haloalkyl), —(C 0-3 alkylene)-O—(C 1-5 haloalkyl), —(C 0-3 alkylene)-CF 3 , —(C 0-3 alkylene)-CN, —(C 0-3 alkylene)-NO 2 , —(C 0-3 alkylene)-CHO, —(C 0-3 alkylene)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-COOH, —(C 0-3 alkylene)-CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-CO—NH 2 , —(C 0-3 alkylene)-CO—NH(C 1-5 alkyl), —(C 0-3 alkylene)-CO—N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —NH 2 , —(C 0-3 alkylene)-SO 2 —NH(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-SO—(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-carbocyclyl, and —(C 0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety of said —(C 0-3 alkylene)-carbocyclyl and the heterocyclyl moiety of said —(C 0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —OH, —O(C 1-5 alkyl), —O(C 1-5 alkylene)-OH, —O(C 1-5 alkylene)-O(C 1-5 alkyl), —SH, —S(C 1-5 alkyl), —NH 2 , —NH(C 1-5 alkyl), —N(C 1-5 alkyl)(C 1-5 alkyl), halogen, C 1-5 haloalkyl, —O—(C 1-5 haloalkyl), —CF 3 , —CN, —NO 2 , —CHO, —CO—(C 1-5 alkyl), —COOH, —CO—O—(C 1-5 alkyl), —O—CO—(C 1-5 alkyl), —CO—NH 2 , —CO—NH(C 1-5 alkyl), —CO—N(C 1-5 alkyl)(C 1-5 alkyl), —NH—CO—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —SO 2 —NH 2 , —SO 2 —NH(C 1-5 alkyl), —SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —NH—SO 2 —(C 1-5 alkyl), —N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —SO—(C 1-5 alkyl), —SO 2 —(C 1-5 alkyl), cycloalkyl, and heterocycloalkyl;

R 3 is —CH 2 —CF 3 or —CH 2 —SO 2 —CH 3 ;

L is C 1-5 alkylene, wherein one or more —CH 2 — units in said alkylene are each optionally replaced by a group independently selected from —N(R L )—, —N(R L )—CO—, —CO—N(R L )—, —CO—, —O—, —CO—O—, —O—CO—, —S—, —SO—, —SO 2 —, —SO 2 —N(R L )—, and —N(R L )—SO 2 —;

each R L is independently selected from hydrogen and C 1-5 alkyl;

ring A is aryl or monocyclic heteroaryl, wherein said aryl or said monocyclic heteroaryl is optionally substituted with one or more groups R A ; and

each R A is independently selected from C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —(C 0-3 alkylene)-OH, —(C 0-3 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-O(C 1-5 alkylene)-OH, (C 0-3 alkylene)-O(C 1-5 alkylene)-O(C 1-5 alkyl), —(C 0-3 alkylene)-SH, —(C 0-3 alkylene)-S(C 1-5 alkyl), —(C 0-3 alkylene)-NH 2 , —(C 0-3 alkylene)-NH(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-halogen, —(C 0-3 alkylene)-(C 1-5 haloalkyl), —(C 0-3 alkylene)-O—(C 1-5 haloalkyl), —(C 0-3 alkylene)-CF 3 , —(C 0-3 alkylene)-CN, —(C 0-3 alkylene)-NO 2 , —(C 0-3 alkylene)-CHO, —(C 0-3 alkylene)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-COOH, —(C 0-3 alkylene)-CO—O—(C 1-5 alkyl), —(C 0-3 alkylene)-O—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-CO—NH 2 , —(C 0-3 alkylene)-CO—NH(C 1-5 alkyl), —(C 0-3 alkylene)-CO—N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—CO—(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —NH 2 , —(C 0-3 alkylene)-SO 2 —NH(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —(C 0-3 alkylene)-NH—SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-SO—(C 1-5 alkyl), —(C 0-3 alkylene)-SO 2 —(C 1-5 alkyl), —(C 0-3 alkylene)-carbocyclyl, and —(C 0-3 alkylene)-heterocyclyl, wherein the carbocyclyl moiety of said —(C 0-3 alkylene)-carbocyclyl and the heterocyclyl moiety of said —(C 0-3 alkylene)-heterocyclyl are each optionally substituted with one or more groups independently selected from C 1-5 alkyl, C 2-5 alkenyl, C 2-5 alkynyl, —OH, —O(C 1-5 alkyl), —O(C 1-5 alkylene)-OH, —O(C 1-5 alkylene)-O(C 1-5 alkyl), —SH, —S(C 1-5 alkyl), —NH 2 , —NH(C 1-5 alkyl), —N(C 1-5 alkyl)(C 1-5 alkyl), halogen, C 1-5 haloalkyl, —O—(C 1-5 haloalkyl), —CF 3 , —CN, —NO 2 , —CHO, —CO—(C 1-5 alkyl), —COOH, —CO—O—(C 1-5 alkyl), —O—CO—(C 1-5 alkyl), —CO—NH 2 , —CO—NH(C 1-5 alkyl), —CO—N(C 1-5 alkyl)(C 1-5 alkyl), —NH—CO—(C 1-5 alkyl), —N(C 1-5 alkyl)-CO—(C 1-5 alkyl), —SO 2 —NH 2 , —SO 2 —NH(C 1-5 alkyl), —SO 2 —N(C 1-5 alkyl)(C 1-5 alkyl), —NH—SO 2 —(C 1-5 alkyl), —N(C 1-5 alkyl)-SO 2 —(C 1-5 alkyl), —SO—(C 1-5 alkyl), —SO 2 —(C 1-5 alkyl), cycloalkyl, and heterocycloalkyl;

or a pharmaceutically acceptable salt or solvate thereof.

2. The compound of claim 1 , wherein R 2 and R 4 are each independently selected from hydrogen, C 1-5 alkyl, —OH, —O(C 1-5 alkyl), —O(C 1-5 alkylene)-OH, —O(C 1-5 alkylene)-O(C 1-5 alkyl), —SH, —S(C 1-5 alkyl), —NH 2 , —NH(C 1-5 alkyl), —N(C 1-5 alkyl)(C 1-5 alkyl), halogen, C 1-5 haloalkyl, —CF 3 , and —CN.

3. The compound of claim 1 , wherein L is C 1-3 alkylene, wherein one —CH 2 — unit in said alkylene is optionally replaced by a group selected from —N(R L )—, —N(R L )—CO—, —CO—N(R L )—, and —CO—, and further wherein each R L is independently selected from hydrogen, methyl and ethyl.

4. The compound of claim 1 , wherein L is —NH—.

5. The compound of claim 1 , wherein ring A is phenyl or a 6-membered monocyclic heteroaryl, wherein said phenyl or said monocyclic heteroaryl is optionally substituted with one or more groups R A .

6. The compound of claim 1 , wherein ring A is phenyl or pyridin-2-yl, wherein said phenyl or said pyridin-2-yl is optionally substituted with one or more groups R A .

7. The compound of claim 1 , wherein each R A is independently selected from C 1-5 alkyl, —OH, —O(C 1-5 alkyl), —O(C 1-5 alkylene)-OH, —O(C 1-5 alkylene)-O(C 1-5 alkyl), —SH, —S(C 1-5 alkyl), —NH 2 , —NH(C 1-5 alkyl), —N(C 1-5 alkyl)(C 1-5 alkyl), halogen, C 1-5 haloalkyl, —CF 3 , and —CN.

8. A compound, wherein said compound is selected from:

1

[3-(2-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-

oxazepan-4-yl)methanone

2

[3-anilino-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-oxazepan-

4-yl)methanone

3

[3-(2-methoxyanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-

(1,4-oxazepan-4-yl)methanone

4

[3-(2-methylanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-

oxazepan-4-yl)methanone

5

[3-(N-methylanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-

oxazepan-4-yl)methanone

6

[3-(3-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-

oxazepan-4-yl)methanone

7

[3-(3-methoxyanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-

(1,4-oxazepan-4-yl)methanone

8

3-[[6-(1,4-oxazepane-4-carbonyl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-3-yl]amino]benzonitrile

9

3-[[6-(1,4-oxazepane-4-carbonyl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-3-yl]amino]benzamide

10

[3-(4-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-

oxazepan-4-yl)methanone

11

[3-(4-methoxyanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-

(1,4-oxazepan-4-yl)methanone

12

1,4-oxazepan-4-yl-[3-(3-pyridylamino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]methanone

13

4-[[6-(1,4-oxazepane-4-carbonyl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-3-yl]amino]benzonitrile

14

4-[[6-(1,4-oxazepane-4-carbonyl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-3-yl]amino]benzamide

15

[3-(3,5-difluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-

(1,4-oxazepan-4-yl)methanone

16

[3-(3-fluoro-4-methylanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(1,4-oxazepan-4-yl)methanone

17

[3-(3,4-difluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-

(1,4-oxazepan-4-yl)methanone

18

[3-(3-chloro-4-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-

yl]-(1,4-oxazepan-4-yl)methanone

19

[3-(4-chloro-3-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-

yl]-(1,4-oxazepan-4-yl)methanone

20

[3-(3-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(8-

oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone

21

[3-(4-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(8-

oxa-3-azabicyclo[3.2.1]octan-3-yl)methanone

22

[3-(4-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(4-

hydroxy-1-piperidyl)methanone

23

[3-(3-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(4-

hydroxy-1-piperidyl)methanone

24

(4-hydroxy-1-piperidyl)-[3-(2-pyridylamino)-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

25

[3-(3-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(3-

endo-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)methanone

26

[3-(4-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(3-

endo-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)methanone

27

[3-(4-fluoroanilino)-1-(methylsulfonylmethyl)pyrazolo[4,3-c]pyridin-6-yl]-

(1,4-oxazepan-4-yl)methanone

28

[3-(3-fluoroanilino)-1-(methylsulfonylmethyl)pyrazolo[4,3-c]pyridin-6-yl]-

(1,4-oxazepan-4-yl)methanone

29

[3-anilino-1-(methylsulfonylmethyl)pyrazolo[4,3-c]pyridin-6-yl]-(3-endo-

hydroxy-8-azabicyclo[3.2.1]octan-8-yl)methanone

30

[3-(4-fluoroanilino)-1-(methylsulfonylmethyl)pyrazolo[4,3-c]pyridin-6-yl]-(3-

endo-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)methanone

31

[3-(3-fluoroanilino)-1-(methylsulfonylmethyl)pyrazolo[4,3-c]pyridin-6-yl]-(3-

endo-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)methanone

32

[3-(3-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(6-

hydroxy-1,4-oxazepan-4-yl)methanone

33

[3-(4-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(6-

hydroxy-1,4-oxazepan-4-yl)methanone

34

[3-(4-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(4-

hydroxy-4-methyl-1-piperidyl)methanone

35

[3-(3-fluoroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(4-

hydroxy-4-methyl-1-piperidyl)methanone

36

1,4-oxazepan-4-yl-[3-(pyrimidin-2-ylamino)-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

37

[3-(3-chloroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-

oxazepan-4-yl)methanone

38

[3-(4-chloroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-

oxazepan-4-yl)methanone

39

[3-(2-chloroanilino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-

oxazepan-4-yl)methanone

40

(6,6-dideuterio-1,4-oxazepan-4-yl)-[3-(3-fluoroanilino)-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

41

(6,6-dideuterio-1,4-oxazepan-4-yl)-[3-(4-fluoroanilino)-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

42

1,4-oxazepan-4-yl-[3-(2-pyridylamino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]methanone

43

1,4-oxazepan-4-yl-[3-(4-pyridylamino)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]methanone

44

[3-[(5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(1,4-oxazepan-4-yl)methanone

45

[3-[(6-methoxy-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

46

[3-[(4-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(1,4-oxazepan-4-yl)methanone

47

8-oxa-3-azabicyclo[3.2.1]octan-3-yl-[3-(2-pyridylamino)-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

48

[3-[(5-chloro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(1,4-oxazepan-4-yl)methanone

49

[3-[(6-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(1,4-oxazepan-4-yl)methanone

50

[3-[(5-methoxy-3-methyl-2-pyridyl)amino]-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

51

[3-[(6-chloro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(1,4-oxazepan-4-yl)methanone

52

(6-hydroxy-1,4-oxazepan-4-yl)-[3-(2-pyridylamino)-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

53

(4-hydroxy-4-methyl-1-piperidyl)-[3-(2-pyridylamino)-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

54

[3-[(3-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(1,4-oxazepan-4-yl)methanone

55

[3-[(3-chloro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(1,4-oxazepan-4-yl)methanone

56

[3-[(5-fluoro-3-methyl-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

57

[3-[(5-fluoro-4-methyl-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

58

[3-[(5-fluoro-6-methyl-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

59

(6,6-dideuterio-1,4-oxazepan-4-yl)-[3-(2-pyridylamino)-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

60

(6,6-dideuterio-1,4-oxazepan-4-yl)-[3-[(4-fluoro-2-pyridyl)amino]-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

61

1,4-oxazepan-4-yl-[3-(pyrazin-2-ylamino)-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

62

1,4-oxazepan-4-yl-[1-(2,2,2-trifluoroethyl)-3-[[4-(trifluoromethyl)-2-

pyridyl]amino]pyrazolo[4,3-c]pyridin-6-yl]methanone

63

[3-[(4-methoxy-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

64

[3-[(4-chloro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(1,4-oxazepan-4-yl)methanone

65

[3-[(6-chloro-5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

66

[3-[(4-chloro-5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

67

[3-[(3-chloro-5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

68

[3-[(4-methyl-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(1,4-oxazepan-4-yl)methanone

69

1,4-oxazepan-4-yl-[3-(pyridazin-3-ylamino)-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

70

[3-[(4-fluoro-3-methyl-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

71

[3-[(5-chloro-4-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

72

[3-[(3,5-difluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

73

[1,4]Oxazepan-4-yl-[3-(pyrimidin-4-ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-

pyrazolo[4,3-c]pyridin-6-yl]-methanone

74

(4-Hydroxy-piperidin-1-yl)-[3-(pyrazin-2-ylamino)-1-(2,2,2-trifluoro-ethyl)-

1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone

75

[3-(5-Chloro-pyrazin-2-ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-

c]pyridin-6-yl]-(4-hydroxy-piperidin-1-yl)-methanone

76

(4-Hydroxy-piperidin-1-yl)-[3-(pyrimidin-4-ylamino)-1-(2,2,2-trifluoro-ethyl)-

1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone

77

[3-(5-Fluoro-pyridin-2-ylamino)-1-methanesulfonylmethyl-1H-pyrazolo[4,3-

c]pyridin-6-yl]-[1,4]oxazepan-4-yl-methanone

78

[3-(5-Chloro-pyridin-2-ylamino)-1-methanesulfonylmethyl-1H-pyrazolo[4,3-

c]pyridin-6-yl]-[1,4]oxazepan-4-yl-methanone

79

[3-(4-Chloro-pyridin-2-ylamino)-1-methanesulfonylmethyl-1H-pyrazolo[4,3-

c]pyridin-6-yl]-[1,4]oxazepan-4-yl-methanone

80

[3-[(5,6-difluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

81

[3-[(5-fluoro-4-methoxy-2-pyridyl)amino]-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

82

[3-[(5-fluoro-6-methoxy-2-pyridyl)amino]-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

83

[3-(5-Methoxy-pyridin-2-ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-

c]pyridin-6-yl]-[1,4]oxazepan-4-yl-methanone

84

[1,4]Oxazepan-4-yl-[3-(thiazol-5-ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-

pyrazolo[4,3-c]pyridin-6-yl]methanone

85

[1,4]Oxazepan-4-yl-[3-(thiazol-2-ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-

pyrazolo[4,3-c]pyridin-6-yl]methanone

86

6-[6-([1,4]Oxazepane-4-carbonyl)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-

c]pyridin-3-ylamino]-1H-pyridin-2-one

87

3-[[6-(1,4-oxazepane-4-carbonyl)-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridin-3-yl]amino]-1H-pyridin-2-one

88

[3-[(5-fluoro-4-hydroxy-2-pyridyl)amino]-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

89

[3-[(5-fluoro-3-hydroxy-2-pyridyl)amino]-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

90

[3-[(4-fluoro-3-hydroxy-2-pyridyl)amino]-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]-(1,4-oxazepan-4-yl)methanone

91

(6,6-dideuterio-1,4-oxazepan-4-yl)-[3-[(5-fluoro-2-pyridyl)amino]-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

92

[3-[(5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(6-hydroxy-1,4-oxazepan-4-yl)methanone

93

[(6S)-6-fluoro-1,4-oxazepan-4-yl]-[3-[(5-fluoro-2-pyridyl)amino]-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

94

[3-[(5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(4-hydroxypiperidin-1-yl)methanone

95

[3-(5-Fluoro-pyridin-2-ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-

c]pyridin-6-yl]-(4-hydroxy-4-methyl-piperidin-1-yl)-methanone

96

(4-Fluoro-piperidin-1-yl)-[3-(5-fluoro-pyridin-2-ylamino)-1-(2,2,2-trifluoro-

ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone

97

[(3R)-3-hydroxy-piperidin-1-yl]-[3-(5-Fluoro-pyridin-2-ylamino)-1-(2,2,2-

trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]methanone

98

[(3S)-3-hydroxy-piperidin-1-yl]-[3-(5-Fluoro-pyridin-2-ylamino)-1-(2,2,2-

trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]methanone

99

[(3R)-3-fluoro-piperidin-1-yl]-[3-(5-Fluoro-pyridin-2-ylamino)-1-(2,2,2-

trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]methanone

100

[(3S)-3-fluoro-piperidin-1-yl]-[3-(5-Fluoro-pyridin-2-ylamino)-1-(2,2,2-

trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]methanone

101

[3-[(5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-[(3R)-3-(hydroxymethyl)-1-piperidyl]methanone

102

[3-[(5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-[(3S)-3-(hydroxymethyl)-1-piperidyl]methanone

103

(3,3-Difluoro-4-hydroxy-piperidin-1-yl)-[3-(5-fluoro-pyridin-2-ylamino)-1-

(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone

104

[3-[(5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(3-hydroxy-3-methyl-piperidin-1-yl)methanone

105

Cis-[3-(5-Fluoro-pyridin-2-ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-

pyrazolo[4,3-c]pyridin-6-yl]-(3-hydroxy-4-methyl-piperidin-1-yl)-methanone

106

Cis-(3-Fluoro-4-hydroxy-piperidin-1-yl)-[3-(5-fluoro-pyridin-2-ylamino)-1-

(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone

107

[3-[(5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(3-endo-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)methanone

108

1-[3-[(5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-

c]pyridine-6-carbonyl]pyridine-4-carboxylic acid

109

[3-[(4-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(6-hydroxy-1,4-oxazepan-4-yl)methanone

110

[(6S)-6-fluoro-1,4-oxazepan-4-yl]-[3-(4-fluoro-pyridin-2-ylamino)-1-(2,2,2-

trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone

111

[3-[(4-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(4-hydroxypiperidin-1-yl)methanone

112

[3-(4-Fluoro-pyridin-2-ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-

c]pyridin-6-yl]-(4-hydroxy-4-methyl-piperidin-1-yl)-methanone

113

[3-(4-Fluoro-pyridin-2-ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-

c]pyridin-6-yl]-(4-ethyl-4-hydroxypiperidin-1-yl)-methanone

114

[3-(4-Fluoro-pyridin-2-ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-

c]pyridin-6-yl]-(4-isopropyl-4-hydroxypiperidin-1-yl)-methanone

115

[3-(4-Fluoro-pyridin-2-ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-

c]pyridin-6-yl]-(4-cyclopropyl-4-hydroxypiperidin-1-yl)-methanone

116

(4-Fluoro-piperidin-1-yl)-[3-(4-fluoro-pyridin-2-ylamino)-1-(2,2,2-trifluoro-

ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone

117

[(3S)-3-hydroxy-piperidin-1-yl]-[3-(4-fluoro-pyridin-2-ylamino)-1-(2,2,2-

trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]methanone

118

[3-(4-Fluoro-pyridin-2-ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-

c]pyridin-6-yl]-(4-hydroxy-2,2-dimethyl-piperidin-1-yl)-methanone

119

(3,3-Difluoro-4-hydroxy-piperidin-1-yl)-[3-(4-fluoro-pyridin-2-ylamino)-1-

(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone

120

[3-[(4-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-(3-endo-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)methanone

121

6,6-dideuterio-1,4-oxazepan-4-yl)-[3-(pyrazin-2ylamino)-1-(2,2,2-

trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

122

[(6S)-6-fluoro-1,4-oxazepan-4-yl]-[3-(pyrazin-2ylamino)-1-(2,2,2-trifluoro-

ethyl)-1H-pyrazolo[4,3-c]pyridin-6-yl]-methanone

123

[3-(pyrazin-2ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-

yl]-(4-hydroxy-4-methyl-piperidin-1-yl)-methanone

124

[3-(pyrazin-2ylamino)-1-(2,2,2-trifluoro-ethyl)-1H-pyrazolo[4,3-c]pyridin-6-

yl]-(4-fluoro-piperidin-1-yl)-methanone

125

[3-[(5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-[(2R)-2-(2-hydroxy-2-methyl-propyl)pyrrolidin-1-yl]methanone

126

[3-[(5-fluoro-2-pyridyl)amino]-1-(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-

6-yl]-[(2S)-2-(2-hydroxy-2-methyl-propyl)pyrrolidin-1-yl]methanone

127

(3-endo-hydroxy-8-azabicyclo[3.2.1]octan-8-yl)-[3-(2-pyridylamino)-1-

(2,2,2-trifluoroethyl)pyrazolo[4,3-c]pyridin-6-yl]methanone

and pharmaceutically acceptable salts and solvates thereof.

9. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

10. A set or kit comprising separate packs of:

(a) the compound as defined in claim 1 ; and

(b) a further therapeutic agent.

11. The compound of claim 1 , wherein ring A is phenyl, pyridinyl, pyrimidinyl or pyrazinyl, wherein said phenyl, said pyridinyl, said pyrimidinyl and said pyrazinyl are each optionally substituted with one or more groups R A .

12. The compound of claim 1 , wherein each R A is independently halogen.

13. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient and one or more further pharmaceutically active agents.

14. The compound of claim 1 , or a pharmaceutically acceptable salt thereof.

15. The compound of claim 8 , or a pharmaceutically acceptable salt thereof.

Assignments (4)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 15, 2025
From: MERCK PATENT GMBH; MERCK HEALTHCARE KGAA
To: DOMAIN THERAPEUTICS
Reel/Frame 072033/0504 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 21, 2021
From: BLAYO, ANNE-LAURE; MANTEAU, BAPTISTE; AMALRIC, CAMILLE; MAYER, STANISLAS; SCHANN, STEPHAN; FER, MICKAËL
To: DOMAIN THERAPEUTICS SA
Reel/Frame 056315/0922 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 21, 2021
From: DOMAIN THERAPEUTICS SA
To: MERCK HEALTHCARE KGAA
Reel/Frame 056316/0023 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 21, 2021
From: MERCK HEALTHCARE KGAA
To: MERCK PATENT GMBH
Reel/Frame 056316/0166 →
Priority Claims (1)
EP 18306390 · Oct 25, 2018 · regional
Continuity (1)
Related Publication 20210361669A1 · Nov 25, 2021
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