Granted Patent B2

US 12,643,890 · App. 18/062,896 · Granted Jun 2, 2026

Inventors: Virginie Brom (Blotzheim, FR); Luke Green (Basel, CH); Christian Kramer (Lörrach, DE); Dmitry Mazunin (Grenzach-Wyhlen, DE); Emmanuel Pinard (Linsdorf, FR); Hasane Ratni (Habsheim, FR)

Assignee: Hoffmann-La Roche Inc.

C07D413/04C07D403/04

Abstract

Claims (68)

1 . A compound of formula I

or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from the group consisting of

i) 5- or 6-member heteroaryl,

ii) substituted 5- or 6-member heteroaryl,

iii) 5- or 6-member heterocycloalkyl, and

iv) substituted 5- or 6-member heterocycloalkyl,

wherein the substituted 5- or 6-member heteroaryl or substituted 5- or 6-member heterocycloalkyl is substituted with one or more C 1-6 -alkyl substituents;

R 2 is selected from the group consisting of

i) H,

ii) cyano,

iii) halogen,

iv) C 1-6 -alkyl, and

v) halo-C 1-6 -alkyl; and

R 3 is halogen.

2 . A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 3 is Cl.

3 . A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from the group consisting of:

i) H, and

ii) cyano.

4 . A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from the group consisting of

i) 5- or 6-member heteroaryl,

ii) substituted 5- or 6-member heteroaryl, and

iii) substituted 5- or 6-member heterocycloalkyl,

wherein the substituted 5- or 6-member heteroaryl or substituted 5- or 6-member heterocycloalkyl is substituted with one or more C 1-6 -alkyl substituents; and

R 2 is selected from the group consisting of

i) H, and

ii) cyano.

5 . A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein;

R 1 is selected from the group consisting of

i) 5- or 6-member heteroaryl,

ii) substituted 5- or 6-member heteroaryl, and

iii) substituted 5- or 6-member heterocycloalkyl,

wherein the substituted 5- or 6-member heteroaryl or substituted 5- or 6-member heterocycloalkyl is substituted with one or more C 1-6 -alkyl substituents;

R 2 is selected from the group consisting of

i) H, and

ii) cyano; and

R 3 is Cl.

6 . A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein R 1 is selected from the group consisting of 3-methyl-1,2,4-oxadiazol-5-yl, 3-methyl-1,2,4-triazol-1-yl, 3-methylisoxazol-5-yl, 3-methylpyrazol-1-yl, 4-methyloxazol-2-yl, 4-methylpyrazol-1-yl, 4-methyltriazol-2-yl, 5,5-dimethyl-4H-isoxazol-3-yl, 5-methyl-1,3,4-oxadiazol-2-yl, 5-methyloxazol-2-yl, 5-methylpyrazin-2-yl, 5-methylpyrimidin-2-yl, oxazol-2-yl, pyrazin-2-yl, and pyridazin-3-yl.

7 . A compound according to claim 1 , or a pharmaceutically acceptable salt thereof, wherein:

R 1 is selected from the group consisting of 3-methyl-1,2,4-oxadiazol-5-yl, 3-methyl-1,2,4-triazol-1-yl, 3-methylisoxazol-5-yl, 3-methylpyrazol-1-yl, 4-methyloxazol-2-yl, 4-methylpyrazol-1-yl, 4-methyltriazol-2-yl, 5,5-dimethyl-4H-isoxazol-3-yl, 5-methyl-1,3,4-oxadiazol-2-yl, 5-methyloxazol-2-yl, 5-methylpyrazin-2-yl, 5-methylpyrimidin-2-yl, oxazol-2-yl, pyrazin-2-yl, and pyridazin-3-yl;

R 2 is selected from the group consisting of

i) H, and

ii) cyano; and

R 3 is Cl.

8 . A compound according to claim 1 , selected from the group consisting of

N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)pyrimidin-2-amine;

N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-5-(5-methyl-1,3,4-oxadiazol-2-yl)pyrimidin-2-amine;

N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-5-(4-methyloxazol-2-yl)pyrimidin-2-amine;

N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-5-(3-methylisoxazol-5-yl)pyrimidin-2-amine;

N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-5-(4-methyl-1H-pyrazol-1-yl)pyrimidin-2-amine;

N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-5-(3-methyl-1H-pyrazol-1-yl)pyrimidin-2-amine;

N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-5-(4-methyltriazol-2-yl)pyrimidin-2-amine;

N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-5-(5-methyloxazol-2-yl)pyrimidin-2-amine;

(S or R)—N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)pyrimidin-2-amine;

(R or S)—N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-5-(3-methyl-1,2,4-oxadiazol-5-yl)pyrimidin-2-amine;

N-(5-chloro-2,3-dihydro-1H-inden-2-yl)-5-(5,5-dimethyl-4,5-dihydroisoxazol-3-yl)pyrimidin-2-amine;

(S)-6-chloro-2-((5-(3-methyl-1,2,4-oxadiazol-5-yl)pyrimidin-2-yl)amino)-2,3-dihydro-1H-indene-4-carbonitrile;

(S)-6-chloro-2((5-(3-methylisoxazol-5-yl)pyrimidin-2-yl)amino)-2,3-dihydro-1H-indene-4-carbonitrile;

(S)-6-chloro-2-((5-(4-methyloxazol-2-yl)pyrimidin-2-yl)amino)-2,3-dihydro-1H-indene-4-carbonitrile;

(S)-6-chloro-2-((5-(5-methyloxazol-2-yl)pyrimidin-2-yl)amino)-2,3-dihydro-1H-indene-4-carbonitrile;

(S)-6-chloro-2-((5-(5-methylpyrazin-2-yl)pyrimidin-2-yl)amino)-2,3-dihydro-1H-indene-4-carbonitrile;

(S)-6-chloro-2-((5-methyl-[2,5″-bipyrimidin]-2″-yl)amino)-2,3-dihydro-1H-indene-4-carbonitrile; and

(S)-6-chloro-2-[[5-(3-methyl-1,2,4-triazol-1-yl)pyrimidin-2-yl]amino]-2,3-dihydro-1H-indene-4-carbonitrile;

or a pharmaceutically acceptable salt thereof.

9 . A process to prepare a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, the process comprising the reaction of a compound of formula II with a compound of formula III to provide a compound of formula I, wherein R 1 , R 2 , and R 3 are as defined in claim 1 and X is halogen or a thiomethyl group:

10 . A pharmaceutical composition comprising a compound according to claim 1 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

11 . A pharmaceutical composition comprising a compound according to claim 8 , or a pharmaceutically acceptable salt thereof, and a therapeutically inert carrier.

Assignments (2)

Priority Claims (1)

Continuity (2)

References Cited (16)