IP Library › Granted Patent US 9,371,336

Granted Patent B2

US 9,371,336 · App. 14/380,385 · Granted Jun 21, 2016

Compounds for treating spinal muscular atrophy

Inventors: Chang-Sun Lee (Belle Mead, NJ); Soongyu Choi (Belle Mead, NJ); Gary Mitchell Karp (Princeton Junction, NJ); Hiroo Koyama (Tokyo, JP); Hasane Ratni (Habsheim, FR)

Assignees: PTC Therapeutics, Inc.; F. Hoffmann-La Roche AG

C07D519/00 C07D491/04 C07D491/052

View Patent ↗

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US 9,371,336
App. No.: 14/380,385
Granted: Jun 21, 2016
Kind: B2

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

Provided herein are compounds, compositions thereof and uses therewith for treating spinal muscular atrophy.

Claims (192)

1. A compound of Formula (IIa1) or Formula (IIIa1), respectively:

or a free acid, free base, salt, stereoisomer, racemate, enantiomer, diastereomer or tautomer thereof, wherein

R 1 is heterocyclyl optionally substituted with one, two or three R 3 substituents and optionally, with one additional R 4 substituent, or optionally substituted with one, two, three or four R 3 substituents;

R 2 is heteroaryl optionally substituted with one, two or three R 6 substituents and optionally, with one additional R 7 substituent;

R a is hydrogen;

R b is hydrogen;

R 3 is, in each instance, independently selected from cyano, halogen, hydroxy, oxo, C 1-8 alkyl, halo-C 1-8 alkyl, C 1-8 alkyl-carbonyl, C 1-8 alkoxy, halo-C 1-8 alkoxy, C 1-8 alkoxy-C 1-8 alkyl, C 1-8 alkoxy-carbonyl, amino, C 1-8 alkyl-amino, (C 1-8 alkyl) 2 -amino, amino-C 1-8 alkyl, C 1-8 alkyl-amino-C 1-8 alkyl, (C 1-8 alkyl) 2 -amino-C 1-8 alkyl, amino-C 1-8 alkyl-amino, C 1-8 alkyl-amino-C 1-8 alkyl-amino, (C 1-8 alkyl-amino-C 1-8 alkyl) 2 -amino, (C 1-8 alkyl) 2 -amino-C 1-8 alkyl-amino, [(C 1-8 alkyl) 2 -amino-C 1-8 alkyl] 2 -amino, (C 1-8 alkyl-amino-C 1-8 alkyl)(C 1-8 alkyl)amino, [(C 1-8 alkyl) 2 -amino-C 1-8 alkyl](C 1-8 alkyl)amino, C 1-8 alkoxy-C 1-8 alkyl-amino, (C 1-8 alkoxy-C 1-8 alkyl) 2 -amino, (C 1-8 alkoxy-C 1-8 alkyl)(C 1-8 alkyl)amino, C 1-8 alkyl-carbonyl-amino, C 1-8 alkoxy-carbonyl-amino, hydroxy-C 1-8 alkyl, hydroxy-C 1-8 alkoxy-C 1-8 alkyl, hydroxy-C 1-8 alkyl-amino, (hydroxy-C 1-8 alkyl) 2 -amino or (hydroxy-C 1-8 alkyl)(C 1-8 alkyl)amino;

R 4 is C 3-14 cycloalkyl, C 3-14 cycloalkyl-C 1-8 alkyl, C 3-14 cycloalkyl-amino, aryl-C 1-8 alkyl, aryl-C 1-8 alkoxy-carbonyl, aryl-sulfonyloxy-C 1-8 alkyl, heterocyclyl or heterocyclyl-C 1-8 alkyl; wherein, each instance of C 3-14 cycloalkyl, aryl and heterocyclyl is optionally substituted with one, two or three R 5 substituents;

R 5 is, in each instance, independently selected from halogen, hydroxy, cyano, nitro, C 1-8 alkyl, halo-C 1-8 alkyl, C 1-8 alkoxy, halo-C 1-8 alkoxy, amino, C 1-8 alkyl-amino, (C 1-8 alkyl) 2 -amino or C 1-8 alkyl-thio;

R 6 is, in each instance, independently selected from halogen, hydroxy, cyano, nitro, C 1-8 alkyl, C 2-8 alkenyl, halo-C 1-8 alkyl, hydroxy-C 1-8 alkyl, C 1-8 alkoxy, halo-C 1-8 alkoxy, C 1-8 alkoxy-C 1-8 alkyl, amino, C 1-8 alkyl-amino, (C 1-8 alkyl) 2 -amino or C 1-8 alkyl-thio; and,

R 7 is C 3-14 cycloalkyl, C 3-14 cycloalkyl-oxy, aryl, heterocyclyl or heteroaryl.

2. The compound of claim 1 , wherein the salt form is a chloride, hydrobromide, hydrochloride, dihydrochloride, acetate, trifluoroacetate or trifluoroacetic acid salt.

3. The compound of claim 1 , wherein the compound is selected from the group consisting of:

3-(1,3-benzothiazol-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(1,3-benzothiazol-2-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(1,3-benzothiazol-2-yl)-7-[4-(2-chloroethyl)piperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-[4-(2-hydroxybenzyl)piperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

tert-butyl 4-[3-(1,3-benzothiazol-2-yl)-2-oxo-2H-pyrano[3,2-c]pyridin-7-yl]piperazine-1-carboxylate

tert-butyl 4-[3-(4-chloro-1,3-benzothiazol-2-yl)-2-oxo-2H-pyrano[3,2-c]pyridin-7-yl]piperazine-1-carboxylate

3-(4-chloro-1,3-benzothiazol-2-yl)-7-(piperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-[4-(2-hydroxyethyl)piperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-(4-ethylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-(4-propylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(1,3-benzothiazol-2-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one

3-(4-methyl-1,3-thiazol-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(piperazin-1-yl)-3-[4-(trifluoromethyl)-1,3-thiazol-2-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(1,3-benzothiazol-2-yl)-7-(4-ethylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(1,3-benzothiazol-2-yl)-7-(4-propylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(1,3-benzothiazol-2-yl)-7-[4-(propan-2-yl)piperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

7-(4-ethylpiperazin-1-yl)-3-(4-methyl-1,3-thiazol-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(4-methyl-1,3-thiazol-2-yl)-7-(4-propylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-[4-(2,3-dihydroxypropyl)piperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-[4-(propan-2-yl)piperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(6-methylimidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(1,3-benzothiazol-2-yl)-7-[4-(2-hydroxyethyl)piperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(1,3-benzothiazol-2-yl)-7-[4-(2,3-dihydroxypropyl)piperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(6-methylimidazo[1,2-a]pyridin-2-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(7-methylimidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(1,4-diazepan-1-yl)-3-(imidazo[1,2-a]pyrimidin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-(1,4-diazepan-1-yl)-2H-pyrano[2,3-a]pyridin-2-one

7-(1,4-diazepan-1-yl)-3-(imidazo[2,1-b][1,3]thiazol-6-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(6-methylimidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one

3-(6-methylimidazo[1,2-a]pyridin-2-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one

3-(8-chloro-6-methylimidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one

3-(imidazo[1,2-a]pyrimidin-2-yl)-7-(4-methyl-1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-(4-methyl-1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[1,2-a]pyridin-2-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(7-methylimidazo[1,2-a]pyridin-2-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(7-methylimidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one

3-(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)-7-(piperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one

3-(imidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one

3-(5-methylpyrazolo[1,5-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[2,1-b][1,3]thiazol-6-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(1,4-diazepan-1-yl)-3-(imidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(1,4-diazepan-1-yl)-3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(8-chloroimidazo[1,2-a]pyridin-2-yl)-7-(1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[1,2-a]pyridin-2-yl)-7-(4-methyl-1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-7-(4-methyl-1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(8-chloroimidazo[1,2-a]pyridin-2-yl)-7-(4-methyl-1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(1,3-benzothiazol-2-yl)-7-(1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(1,3-benzoxazol-2-yl)-7-(1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-methylpiperazin-1-yl)-3-(5-methylpyrazolo[1,5-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[2,1-b][1,3]thiazol-6-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one

3-(1,3-benzothiazol-2-yl)-7-(4-methyl-1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(7-methylimidazo[1,2-a]pyridin-2-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one

3-(7-methylimidazo[1,2-a]pyridin-2-yl)-7-[(3S)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(7-methylimidazo[1,2-a]pyridin-2-yl)-7-[(2S)-2-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3-(imidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(3S)-3,4-dimethylpiperazin-1-yl]-3-(7-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(2S)-2,4-dimethylpiperazin-1-yl]-3-(7-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-7-[(2S)-2-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-7-[(3S)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

7-(1,4-diazepan-1-yl)-3-(7-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(1,4-diazepan-1-yl)-3-(6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3-(6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(2S)-2,4-dimethylpiperazin-1-yl]-3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(3S)-3,4-dimethylpiperazin-1-yl]-3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(6-methylimidazo[1,2-a]pyridin-2-yl)-7-[(3S)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(6-methylimidazo[1,2-a]pyridin-2-yl)-7-[(3R)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

7-[(3S)-3,4-dimethylpiperazin-1-yl]-3-(6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(3R)-3,4-dimethylpiperazin-1-yl]-3-(6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(8-chloroimidazo[1,2-a]pyridin-2-yl)-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3-(imidazo[1,2-a]pyrimidin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[1,2-a]pyridin-2-yl)-7-[(3S)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[1,2-a]pyridin-2-yl)-7-[(3R)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

7-[(3S)-3,4-dimethylpiperazin-1-yl]-3-(imidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(3R)-3,4-dimethylpiperazin-1-yl]-3-(imidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[2,1-b][1,3]thiazol-6-yl)-7-[(3S)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[2,1-b][1,3]thiazol-6-yl)-7-[(3R)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(4-chloro-1,3-benzothiazol-2-yl)-7-[(2R,5S)-2,4,5-trimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

7-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-3-(6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-3-(7-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(1,4-diazepan-1-yl)-3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-2H-pyrano[2,3-b] pyri din-2-one

3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-(4-methyl-1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(6-methylimidazo[1,2-a]pyridin-2-yl)-7-[(2R,5S)-2,4,5-trimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(8-chloroimidazo[1,2-a]pyridin-2-yl)-7-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(7-methylimidazo[1,2-a]pyridin-2-yl)-7-[(2R,5S)-2,4,5-trimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-7-[(2R,5S)-2,4,5-trimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(8-chloroimidazo[1,2-a]pyridin-2-yl)-7-[(2R,5S)-2,4,5-trimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3-(7-methylimidazo[1,2-a]pyrimidin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3-(7-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3-(6-methylimidazo[1,2-a]pyrazin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-3-(6-methylimidazo[1,2-a]pyrazin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(6-methylimidazo[1,2-a]pyrazin-2-yl)-7-[(2R,5S)-2,4,5-trimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

7-(1,4-diazepan-1-yl)-3-(6-methylimidazo[1,2-a]pyrazin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-methyl-1,4-diazepan-1-yl)-3-(6-methylimidazo[1,2-a]pyrazin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(3R,5S)-3,5-dimethylpiperazin-1-yl]-3-(8-fluoro-6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(1,4-diazepan-1-yl)-3-(8-fluoro-6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(8-chloroimidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(8-chloroimidazo[1,2-a]pyridin-2-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[1,2-a]pyrimidin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(8-fluoro-6-methylimidazo[1,2-a]pyridin-2-yl)-7-(4-methyl-1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[2,1-b][1,3]thiazol-6-yl)-7-(4-methyl-1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-methyl-1,4-diazepan-1-yl)-3-(7-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-methyl-1,4-diazepan-1-yl)-3-(6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[1,2-a]pyrimidin-2-yl)-7-(4-methylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[1,2-a]pyrimidin-2-yl)-7-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-7-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(8-chloroimidazo[1,2-a]pyridin-2-yl)-7-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(imidazo[1,2-a]pyridin-2-yl)-7-[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

7-[(2R,5S)-2,5-dimethylpiperazin-1-yl]-3-(8-fluoro-6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-[(2R,5S)-2,4,5-trimethylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

7-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]-3-(6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]hept-2-yl]-3-(6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-ethyl-1,4-diazepan-1-yl)-3-(imidazo[1,2-a]pyrimidin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-ethyl-1,4-diazepan-1-yl)-3-(imidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-(4-ethyl-1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(3R,5S)-4-ethyl-3,5-dimethylpiperazin-1-yl]-3-(imidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-ethylpiperazin-1-yl)-3-(6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-ethylpiperazin-1-yl)-3-(7-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-ethylpiperazin-1-yl)-3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(8-chloroimidazo[1,2-a]pyridin-2-yl)-7-(4-ethylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-ethylpiperazin-1-yl)-3-(8-fluoro-6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]-3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(1S,4S)-2,5-diazabicyclo[2.2.1]hept-2-yl]-3-(8-fluoro-6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(3S)-4-ethyl-3-methylpiperazin-1-yl]-3-(8-fluoro-6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-ethyl-1,4-diazepan-1-yl)-3-(8-fluoro-6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-ethyl-1,4-diazepan-1-yl)-3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-(4-ethylpiperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(8-chloroimidazo[1,2-a]pyridin-2-yl)-7-(4-ethyl-1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-(4-ethyl-1,4-diazepan-1-yl)-3-(6-methylimidazo[1,2-a]pyrazin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

7-[(3S)-4-ethyl-3-methylpiperazin-1-yl]-3-(6-methylimidazo[1,2-a]pyrazin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one

3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-[(3S)-4-ethyl-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

3-(8-chloroimidazo[1,2-a]pyridin-2-yl)-7-[(3S)-4-ethyl-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one, or

3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-[(3S)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one

or a salt, stereoisomer, racemate, enantiomer, diastereomer or tautomer thereof.

4. The compound of claim 2 , wherein a salt form of the compound is selected from:

3-(4-chloro-1,3-benzothiazol-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(4-chloro-1,3-benzothiazol-2-yl)-7-(piperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one hydrochloride

3-(4-methyl-1,3-thiazol-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

7-(piperazin-1-yl)-3-[4-(trifluoromethyl)-1,3-thiazol-2-yl]-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(6-methylimidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(imidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(7-methylimidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

7-(1,4-diazepan-1-yl)-3-(imidazo[1,2-a]pyrimidin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(4-chloro-1,3-benzothiazol-2-yl)-7-(1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

7-(1,4-diazepan-1-yl)-3-(imidazo[2,1-b][1,3]thiazol-6-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(8-chloro-6-methylimidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one hydrochloride

3-(7-methylimidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one hydrochloride

3-(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)-7-(piperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one hydrochloride

3-(imidazo[1,2-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[3,2-c]pyridin-2-one hydrochloride

3-(5-methylpyrazolo[1,5-a]pyridin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(imidazo[2,1-b][1,3]thiazol-6-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

7-(1,4-diazepan-1-yl)-3-(imidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

7-(1,4-diazepan-1-yl)-3-(8-fluoroimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(8-chloroimidazo[1,2-a]pyridin-2-yl)-7-(1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(1,3-benzothiazol-2-yl)-7-(1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(1,3-benzoxazol-2-yl)-7-(1,4-diazepan-1-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(imidazo[1,2-a]pyridin-2-yl)-7-[(3S)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(imidazo[1,2-a]pyridin-2-yl)-7-[(3R)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(imidazo[2,1-b][1,3]thiazol-6-yl)-7-[(3S)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

3-(imidazo[2,1-b][1,3]thiazol-6-yl)-7-[(3R)-3-methylpiperazin-1-yl]-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

7-(1,4-diazepan-1-yl)-3-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

7-(1,4-diazepan-1-yl)-3-(6-methylimidazo[1,2-a]pyrazin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

7-(1,4-diazepan-1-yl)-3-(8-fluoro-6-methylimidazo[1,2-a]pyridin-2-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride, or

3-(imidazo[1,2-a]pyrimidin-2-yl)-7-(piperazin-1-yl)-2H-pyrano[2,3-b]pyridin-2-one hydrochloride

or a stereoisomer, racemate, enantiomer, diastereomer or tautomer thereof.

5. A pharmaceutical composition comprising an effective amount of the compound of claim 1 and a pharmaceutically acceptable carrier, excipient or diluent.

Assignments (2)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 27, 2015

From: LEE, CHANG-SUN; CHOI, SOONGYU; KARP, GARY MITCHELL; KOYAMA, HIROO

To: PTC THERAPEUTICS, INC.

Reel/Frame 035054/0329 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Feb 27, 2015

From: RATNI, HASANE

To: F. HOFFMANN-LA ROCHE AG

Reel/Frame 035054/0600 →

Continuity (2)

Provisional Application 61605487 · Mar 1, 2012

Related Publication 20150166575A1 · Jun 18, 2015