# US 10,501,482 B2 · Compounds for treating spinal muscular atrophy

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- Number: US 10,501,482 B2
- Document ID: US10501482B2
- Status: Granted
- Kind: B2
- Application number: 15/948,444
- Filed: 2018-04-09
- Published: 2018-08-09
- Granted: 2019-12-10
- Earliest claimed: 2013-06-25
- Assignees: Hoffmann-La Roche Inc.; PTC Therapeutics, Inc.
- Applicants: Hoffmann-La Roche Inc.; PTC Therapeutics Inc.
- Inventors: Amal Dakka; Luke Green; Gary Karp; Jana Narasimhan; Nikolai Naryshkin; Emmanuel Pinard; Hongyan Qi; Hasane Ratni; Nicole Risher; Marla Weetall; Matthew Woll
- Web page: https://patentgrep.com/patent/US10501482B2

## CPC

- C07D 519/00: Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
- A61P 21/00: Drugs for disorders of the muscular or neuromuscular system
- A61P 21/04: for myasthenia gravis
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/02: for peripheral neuropathies
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D 263/56: with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 2
- C07D 413/12: linked by a chain containing hetero atoms as chain links
- C07D 471/04: Ortho-condensed systems
- C07D 487/04: Ortho-condensed systems
- C07D 487/10: Spiro-condensed systems
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The present invention provides compounds of formula (I) wherein A, B, X, Y, R1 and R2 are as described herein, as well as pharmaceutically acceptable salts thereof. Further the present invention is concerned with the manufacture of the compounds of formula (I), pharmaceutical compositions comprising them and their use as medicaments.

## Claims

### Claim 1

A compound of formula (I):
wherein:
X is N or CR3;
Y is N or CR4; with the proviso that not both X and Y are N;
A is a bicyclic 9-membered heteroaryl comprising two or three heteroatoms independently selected from N or O, wherein A can be optionally substituted with one, two or three R5;
B is a saturated or partially unsaturated mono- or bicyclic 4 to 9-membered heterocycloalkyl comprising one or two ring nitrogen atoms, the remaining ring atoms being carbon, wherein B can be optionally substituted with one, two or three R6;
R1 is hydrogen, halo, C1-7-alkyl, C1-7-haloalkyl, C1-7-alkoxy or C1-7-haloalkoxy;
R2 is hydrogen, halo, C1-7-alkyl, C1-7haloalkyl, C1-7-alkoxy or C1-7-haloalkoxy;
R3 is hydrogen, halo, C1-7-alkyl, C1-7-haloalkyl, C1-7-alkoxy or C1-7-haloalkoxy;
R4 is hydrogen, halo, C1-7-alkyl, C1-7-haloalkyl, C1-7-alkoxy or C1-7-haloalkoxy;
each R5 is independently selected from halo, cyano, C1-7-alkyl, C1-7-haloalkyl or C3-7-cycloalkyl;
each R6 is independently selected from C1-7-alkyl, or two R6 together form a C2-7-alkylene;
or a pharmaceutically acceptable salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein A is selected from the group of imidazo[1,2-a]pyrazin-2-yl, imidazo[1,2-a]pyridinyl, and benzo[d]oxazolyl, which can be optionally substituted with one, two or three R5.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein A is selected from the group of imidazo[1,2-a]pyrazin-2-yl substituted with two C1-7-alkyl, imidazo[1,2-a]pyridin-6-yl substituted with one or two C1-7-alkyl, imidazo[1,2-a]pyridin-6-yl substituted with one C1-7-alkyl and one halo, imidazo[1,2-a]pyridin-6-yl substituted with one C1-7-alkyl and one C1-7-haloalkyl, benzo[d]oxazol-6-yl substituted with one C1-7-alkyl, and benzo[d]oxazol-6-yl substituted with one C1-7-alkyl and one halo.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein A is selected from 2-methylbenzo[d]oxazol-6-yl, 4-fluoro-2-methylbenzo[d]oxazol-6-yl, 6,8-dimethylimidazo[1,2-a]pyrazin-2-yl, 2-methylimidazo[1,2-a]pyridin-6-yl, 2,7-dimethylimidazo[1,2-a]pyridin-6-yl, 2,8-dimethylimidazo[1,2-a]pyridin-6-yl, 2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl, 8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl, and 8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein each R5 is independently selected from halo, C1-7-alkyl, or C1-7-haloalkyl.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein each R5 is independently selected from methyl, fluoro, chloro, and trifluoromethyl.

### Claim 7 (depends on 1)

The compound according to claim 1, wherein B as defined herein is further characterized in that one ring nitrogen atoms is basic.

### Claim 8 (depends on 1)

The compound according to claim 1, wherein B is selected from 1,2,3,6-tetrahydropyridinyl, 2,6-diazaspiro[3.3]heptanyl, hexahydropyrrolo[3,4-c]pyrrolyl, hexahydropyrrolo[1,2-a]pyrazinyl, piperazinyl, and piperidinyl, wherein each can be optionally substituted with one, two or three R6.

### Claim 9 (depends on 1)

The compound according to claim 1, wherein B is selected from piperazin-1-yl, 3-methyl-piperazin-1-yl, and 3,3-dimethylpiperazin-1-yl.

### Claim 10 (depends on 1)

The compound according to claim 1, wherein each R6 is C1-7-alkyl.

### Claim 11 (depends on 1)

The compound according to claim 1, wherein each R6 is independently selected from methyl, and ethyl.

### Claim 12 (depends on 1)

The compound according to claim 1, wherein X is CR3 and Y is CR4, or X is N and Y is CR4, or X is CR3 and Y is N.

### Claim 13 (depends on 1)

The compound according to claim 1, wherein X is CR3 and Y is CR4.

### Claim 14 (depends on 1)

The compound according to claim 1, wherein X is N and Y is CR4.

### Claim 15 (depends on 1)

The compound according to claim 1, wherein R1 is hydrogen, halo, C1-7-alkoxy or C1-7-haloalkoxy.

### Claim 16 (depends on 1)

The compound according to claim 1, wherein R1 is hydrogen, fluoro, methoxy, ethoxy or trifluoroethoxy.

### Claim 17 (depends on 1)

The compound according to claim 1, wherein R1 is hydrogen.

### Claim 18 (depends on 1)

The compound according to claim 1, wherein R2 is hydrogen, halo, or C1-7-alkyl.

### Claim 19 (depends on 1)

The compound according to claim 1, wherein R2 is hydrogen, fluoro or methyl.

### Claim 20 (depends on 1)

The compound according to claim 1, wherein R2 is hydrogen.

### Claim 21 (depends on 1)

The compound according to claim 1, wherein R3 is hydrogen or fluoro.

### Claim 22 (depends on 1)

The compound according to claim 1, wherein R3 is hydrogen.

### Claim 23 (depends on 1)

The compound according to claim 1, wherein R4 is hydrogen, halo or C1-7-alkoxy.

### Claim 24 (depends on 1)

The compound according to claim 1, wherein R4 is hydrogen, fluoro, methoxy, ethoxy or trifluoroethoxy.

### Claim 25 (depends on 1)

The compound according to claim 1, wherein R4 is hydrogen or fluoro.

### Claim 26 (depends on 1)

The compound according to claim 1, wherein R4 is hydrogen, halo or C1-7-alkoxy.

### Claim 27 (depends on 1)

The compound according to claim 1, selected from the group consisting of:
N-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-4-(piperazin-1-yl)benzamide;
rac-N-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-4-(3-methylpiperazin-1-yl)benzamide;
N-(6,8-Dimethyl-imidazo[1,2-a]pyrazin-2-yl)-4-((S)-3-methyl-piperazin-1-yl)-benzamide;
N-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-2-fluoro-4-(4-methylpiperazin-1-yl)benzamide;
rac-N-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-2-fluoro-4-(3-methylpiperazin-1-yl)benzamide;
N-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-6-(4-methylpiperazin-1-yl)nicotinamide;
rac-N-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-6-(3-methylpiperazin-1-yl)nicotinamide;
N-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-6-(4-ethylpiperazin-1-yl)nicotinamide;
N-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-5-(4-methylpiperazin-1-yl)picolinamide;
rac-N-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-5-(3-methylpiperazin-1-yl)picolinamide;
N-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-5-(piperazin-1-yl)picolinamide;
rac-N-(2-methylimidazo[1,2-a]pyridin-6-yl)-6-(3-methylpiperazin-1-yl)nicotinamide;
6-(3,3-dimethylpiperazin-1-yl)-N-(2-methylimidazo[1,2-a]pyridin-6-yl)nicotinamide;
N-(2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)nicotinamide;
6-hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)-N-(2-methylimidazo[1,2-a]pyridin-6-yl)nicotinamide;
N-(2-methylimidazo[1,2-a]pyridin-6-yl)-6-(2,6-diazaspiro[3.3]heptan-2-yl)nicotinamide;
rac-N-(2-methylimidazo[1,2-a]pyridin-6-yl)-5-(3-methylpiperazin-1-yl)picolinamide;
rac-2-fluoro-N-(2-methylimidazo[1,2-a]pyridin-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
N-(2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)nicotinamide:
rac-N-(2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl)-6-(3-methylpiperazin-1-yl)nicotinamide;
(S)-6-(hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)-N-(2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl)nicotinamide;
6-(3,5-dimethylpiperazin-1-yl)-N-(2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl)nicotinamide;
6-(3,5-dimethylpiperazin-1-yl)-N-(4-fluoro-2-methylbenzo[d]oxazol-6-yl)nicotinamide;
N-(4-fluoro-2-methylbenzo[d]oxazol-6-yl)-6-(4-methylpiperazin-1-yl)nicotinamide;
(S)—N-(4-fluoro-2-methylbenzo[d]oxazol-6-yl)-6-(hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)nicotinamide;
N-(4-Fluoro-2-methyl-benzooxazol-6-yl)-6-piperazin-1-yl-nicotinamide;
rac-N-(4-Fluoro-2-methyl-benzooxazol-6-yl)-6-(3-methyl-piperazin-1-yl)-nicotinamide;
N-(4-fluoro-2-methylbenzo[d]oxazol-6-yl)-4-(piperazin-1-yl)benzamide;
rac-N-(4-fluoro-2-methylbenzo[d]oxazol-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
4-(3,5-dimethylpiperazin-1-yl)-N-(4-fluoro-2-methylbenzo[d]oxazol-6-yl)benzamide;
(S)-2-fluoro-4-(hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)-N-(2-methylimidazo[1,2-a]pyridin-6-yl)benzamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(4-methylpiperazin-1-yl)nicotinamide;
(S)-2-Fluoro-N-(4-fluoro-2-methyl-benzooxazol-6-yl)-4-(S)-hexahydro-pyrrolo[1,2-a]pyrazin-2-yl-benzamide;
(R)-2-fluoro N-(4-fluoro-2-methylbenzo[d]oxazol-6-yl)-4-(hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)benzamide;
(S)-2-fluoro-4-(hexahydropyrrolo[1,2-a]pyrazin-2(1H)-yl)-N-(2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl)benzamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(piperazin-1-yl)benzamide;
rac-N-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-2-fluoro-4-(3-methylpiperazin-1-yl)benzamide;
rac-2-fluoro-N-(2-methylbenzo[d]oxazol-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
rac-2-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
2-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(piperazin-1-yl)benzamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)nicotinamide;
rac-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(3-methylpiperazin-1-yl)nicotinamide;
rac-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-5-(3-methylpiperazin-1-yl)picolinamide;
2-fluoro-N-(2-methylimidazo[1,2-a]pyridin-6-yl)-4-(piperazin-1-yl)benzamide;
rac-2,3-difluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
rac-2,5-difluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
rac-5-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(3-methylpiperazin-1-yl)nicotinamide;
rac-3-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-5-(3-methylpiperazin-1-yl)picolinamide;
rac-2,6-difluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
(S)-2-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
(R)-2-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
rac-N-(2,7-dimethylimidazo[1,2-a]pyridin-6-yl)-2-fluoro-4-(3-methylpiperazin-1-yl)benzamide;
rac-N-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-5-fluoro-6-(3-methylpiperazin-1-yl)nicotinamide;
rac-N-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-2-fluoro-4-(3-methylpiperazin-1-yl)benzamide;
rac-N-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(3-methylpiperazin-1-yl)nicotinamide;
rac-N-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-3-fluoro-5-(3-methylpiperazin-1-yl)picolinamide;
rac-N-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-2,6-difluoro-4-(3-methylpiperazin-1-yl)benzamide;
2-fluoro-N-(4-fluoro-2-methylbenzo[d]oxazol-6-yl)-4-(piperazin-1-yl)benzamide;
2-fluoro-N-(2-methyl-8-(trifluoromethyl)imidazo[1,2-a]pyridin-6-yl)-4-(piperazin-1-yl)benzamide;
2-fluoro-N-(2-methylimidazo[1,2-a]pyridin-6-yl)-4-(1,2,3,6-tetrahydropyridin-4-yl)benzamide;
2-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(1,2,3,6-tetrahydropyridin-4-yl)benzamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(1,2,3,6-tetrahydropyridin-4-yl)nicotinamide;
N-(2-methylimidazo[1,2-a]pyridin-6-yl)-5-(1,2,3,6-tetrahydropyridin-4-yl)picolinamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-2-methoxy-6-(piperazin-1-yl)nicotinamide;
2-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)nicotinamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-3-methyl-4-(piperazin-1-yl)benzamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-5-methyl-6-(piperazin-1-yl)nicotinamide;
4-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)nicotinamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-methoxy-6-(piperazin-1-yl)nicotinamide;
4-ethoxy-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)nicotinamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)-4-(2,2,2-trifluoroethoxy)nicotinamide;
2-ethoxy-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)nicotinamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)-2-(2,2,2-trifluoroethoxy)nicotinamide;
rac-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-2-methoxy-6-(3-methylpiperazin-1-yl)nicotinamide;
6-(3,3-dimethylpiperazin-1-yl)-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-2-methoxynicotinamide;
rac-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-methoxy-6-(3-methylpiperazin-1-yl)nicotinamide;
N-(2-methylimidazo[1,2-a]pyridin-6-yl)-6-(1,2,3,6-tetrahydropyridin-4-yl)nicotinamide;
N-(2-methylimidazo[1,2-a]pyridin-6-yl)-6-(1-methylpiperidin-4-yl)nicotinamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperidin-4-yl)nicotinamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(1-methylpiperidin-4-yl)nicotinamide;
2-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(piperidin-4-yl)benzamide; and
rac-6-(3,4-dimethylpiperazin-1-yl)-N-(2-methylimidazo[1,2-a]pyridin-6-yl)nicotinamide;
or a pharmaceutically acceptable salt thereof.

### Claim 28 (depends on 1)

The compound according to claim 1, selected from the group consisting of:
rac-2-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
2-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(piperazin-1-yl)benzamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)nicotinamide;
rac-3-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-5-(3-methylpiperazin-1-yl)picolinamide;
rac-2,6-difluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
(S)-2-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
(R)-2-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(3-methylpiperazin-1-yl)benzamide;
rac-N-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-2-fluoro-4-(3-methylpiperazin-1-yl)benzamide;
rac-N-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-3-fluoro-5-(3-methylpiperazin-1-yl)picolinamide;
2-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-(1,2,3,6-tetrahydropyridin-4-yl)benzamide;
N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(1,2,3,6-tetrahydropyridin-4-yl)nicotinamide;
4-fluoro-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)nicotinamide;
4-ethoxy-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)nicotinamide;
2-ethoxy-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-6-(piperazin-1-yl)nicotinamide;
rac-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-2-methoxy-6-(3-methylpiperazin-1-yl)nicotinamide; and
rac-N-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-4-methoxy-6-(3-methylpiperazin-1-yl)nicotinamide;
or a pharmaceutically acceptable salts thereof.

### Claim 29 (depends on 1)

A process for the preparation of a compound according to claim 1, comprising the step of:
a) the Buchwald-Hartwig amination reaction of a compound of formula (II)
with a compound of formula B—H, in the presence of a catalyst and a ligand and a base and a solvent, wherein the hydrogen H of the compound of formula B—H is bound to a ring nitrogen atom of B, V is chloro or bromo, and A, B, X, Y, R1, and R2 are as defined in claim 1; or
b) a nucleophilic aromatic substitution reaction between a compound of formula (II) with a compound of formula B—H by heating in a solvent, wherein the hydrogen H of the compound of formula B—H is bound to a ring nitrogen atom of B, V is fluoro if X is CR3 or V is chloro if X is N, and A, B, X, Y, R1, R2 and R3 are as defined in claim 1; or
c) the Suzuki coupling reaction of a compound of formula (II) with a compound of formula PG-B-pinB in the presence of a base and a catalyst, followed by removal of PG, wherein pinB is pinacolboranyl which is bound to a ring carbon atom of B, PG is an amino-protecting group, V is fluoro or chloro, and wherein A, B, X, Y, R1, and R2 are as defined in claim 1; or
d) the amidation reaction of a compound of formula (III)
with a compound of formula A-NH2 in the presence of a tertiary amine and a coupling reagent, optionally followed by the removal of PG, wherein PG is an optional amino-protecting group, and wherein A, B, X, Y, R1, and R2 are as defined in claim 1.

### Claim 30 (depends on 1)

A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable excipients.

### Claim 31 (depends on 1)

A method for the treatment or prevention of spinal muscular atrophy (SMA), comprising, the step of administering a therapeutically effective amount of a compound according to claim 1, or a pharmaceutically acceptable salt thereof, to a subject in need thereof.