IP Library › Granted Patent US 9,822,103

Granted Patent B2

US 9,822,103 · App. 15/037,066 · Granted Nov 21, 2017

Inhibitors of lysine methyl transferase

Inventors: Steven P. Seitz (Swarthmore, PA); Jay A. Markwalder (Lahaska, PA); Ashok Vinayak Purandare (Pennington, NJ)

Assignee: Bristol-Myers Squibb Company

C07D405/12 A61K31/443 A61K31/444 A61K31/4427 A61K31/496 A61K31/506 A61K31/5377 A61K45/06 C07D405/14 C07D413/14

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Quick Facts

Patent No.: US 9,822,103
App. No.: 15/037,066
Granted: Nov 21, 2017
Kind: B2

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Abstract

There are disclosed compounds that are inhibitors of EZH2, pharmaceutical compositions containing said compounds and methods of treating hyperproliferative, inflammatory, infectious, and immunoregulatory disorders and diseases utilizing the compounds of the invention.

Claims (150)

1. A compound of formula (I)

wherein

the dotted line represents an optional double bond;

Z is O, CH 2 or a direct bond;

R 1 is hydrogen, halogen, CF 3 , optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 8 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, optionally substituted aryl or optionally substituted heterocyclo;

R 2 is hydrogen, halogen, CF 3 , optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 8 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, optionally substituted aryl or optionally substituted heterocyclo;

R 3 is hydrogen, halogen, —CN, —CONR 12 R 13 , optionally substituted C 6 -C 10 mono or bicyclic aryl, optionally substituted C 6 -C 10 mono or bicyclic heteroaryl, optionally substituted C 1 -C 6 alkyl C 6 aryl or optionally substituted C 1 -C 6 alkyl C 5 -C 8 heteroaryl, wherein the optional substituents are halogen, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, —CONR 12 R 13 or heterocyclo;

R 4 , R 5 , R 6 , R 7 and R 8 are independently one or more hydrogen, flourine, CF 3 , optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 8 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, optionally substituted aryl or optionally substituted heterocyclo; or

R 6 and R 7 may be taken together to form a fused C 3 -C 8 cycloalkyl group, or

R 4 and R 6 may be taken together to form a spiro C 4 -C 8 cycloalkyl group; or

R 7 and R 8 may be taken together to form a spiro C 3 -C 8 cycloalkyl group;

R 9 , R 10 and R 11 are independently hydrogen, halogen, CF 3 , optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 8 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, optionally substituted aryl or optionally substituted heterocyclo;

R 12 and R 13 are independently hydrogen, C 1 -C 6 alkyl, or

R 12 and R 13 are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocyclo group;

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.

2. The compound according to claim 1

wherein

R 1 is hydrogen, halogen, CF 3 or optionally substituted C 1 -C 6 alkyl;

R 2 is hydrogen, halogen, CF 3 or optionally substituted C 1 -C 6 alkyl;

R 4 , R 5 , R 6 , R 7 and R 8 are independently one or more hydrogen, flourine, CF 3 or optionally substituted C 1 -C 6 alkyl; or

R 6 and R 7 may be taken together to form a fused C 3 -C 8 cycloalkyl group, or

R 4 and R 6 may be taken together to form a spiro C 4 -C 8 cycloalkyl group; or

R 7 and R 8 may be taken together to form a spiro C 3 -C 8 cycloalkyl group;

R 9 , R 10 and R 11 are independently hydrogen, halogen, CF 3 or optionally substituted C 1 -C 6 alkyl;

R 12 and R 13 are independently hydrogen, C 1 -C 6 alkyl, or

R 12 and R 13 are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocyclo group;

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.

3. A compound of Formula (II)

wherein

Z is O, CH 2 or a direct bond;

R 4 , R 5 , R 6 , R 7 and R 8 are independently one or more hydrogen, fluorine, CF 3 , optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 8 cycloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, optionally substituted aryl or optionally substituted heterocyclo; or

R 6 and R 7 may be taken together to form a fused C 3 -C 8 cycloalkyl group, or

R 7 and R 8 may be taken together to form a spiro C 3 -C 8 cycloalkyl group;

R 12 and R 13 are independently hydrogen, C 1 -C 6 alkyl, or

R 12 and R 13 are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocyclo group;

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.

4. The compound according to claim 3 of the formula

wherein

Z is O, CH 2 or a direct bond;

R 1 is hydrogen, halogen, CF 3 or optionally substituted C 1 -C 6 alkyl;

R 2 is hydrogen, halogen, CF 3 or optionally substituted C 1 -C 6 alkyl;

R 4 , R 5 , R 6 , R 7 and R 8 are independently one or more hydrogen, fluorine, CF 3 or optionally substituted C 1 -C 6 alkyl; or

R 6 and R 7 may be taken together to form a fused C 3 -C 8 cycloalkyl group, or

R 7 and R 8 may be taken together to form a spiro C 3 -C 8 cycloalkyl group;

R 9 , R 10 and R 11 are independently hydrogen, halogen, CF 3 or optionally substituted C 1 -C 6 alkyl;

R 12 and R 13 are independently hydrogen, C 1 -C 6 alkyl, or

R 12 and R 13 are taken together with the nitrogen atom to which they are attached to form an optionally substituted heterocyclo group;

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.

5. The compound which is

7-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-2,3-dihydrobenzofuran-5-carboxamide,

7-Chloro-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2,7-trimethyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-7-(trifluoromethyl)-2,3-dihydrobenzofuran-5-carboxamide,

7-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2,4-trimethyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2,4-trimethyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2,4,7-tetramethyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-7-(4-(morpholinomethyl)phenyl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-7-(6-(piperazin-1-yl)pyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-7-(6-morpholinopyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-7-(quinolin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-methoxypyridin-3-yl)-2,2-dimethyl-2,3-dihydrobenzofuran-5-carboxamide,

(E)-N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-7-styryl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-7-(4-(4-methylpiperazine-1-carbonyl)phenyl)-2,3-dihydrobenzofuran-5-carboxamide,

t-Butyl 4-(5-(5-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)pyrimidin-2-yl)piperazine-1-carboxylate,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-7-(4-(piperazin-1-yl)phenyl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-7-(4-(piperidin-1-ylmethyl)phenyl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-7-(2-(piperazin-1-yl)pyrimidin-5-yl)-2,3-dihydrobenzofuran-5-carboxamide,

7-Benzyl-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-2,3-dihydrobenzofuran-5-carboxamide,

7-Cyano-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethyl-2,3-dihydrobenzofuran-5-carboxamide,

7-Chloro-2,2-dimethyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-2,3-dihydrobenzofuran-5-carboxamide,

7-Bromo-2,2-dimethyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-methoxypyridin-3-yl)-2,2,4-trimethyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2,4-trimethyl-7-(6-(piperazin-1-yl)pyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-7-(6-morpholinopyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-7-(4-(morpholinomethyl)phenyl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-7-(6-(piperazin-1-yl)pyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-methoxypyridin-3-yl)-3-methyl-2,3-dihydrobenzofuran-5-carboxamide,

7-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-methoxypyridin-3-yl)-2-methyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-7-(6-morpholinopyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-7-(6-(piperazin-1-yl)pyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-7-(4-(morpholinomethyl)phenyl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-methoxypyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-morpholinopyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-(piperazin-1-yl)pyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-methoxypyridin-3-yl)-3,3-dimethyl-2,3-dihydrobenzofuran-5-carboxamide,

(2S,3R)-7-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,3-dimethyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethylchroman-6-carboxamide,

8-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2,2-dimethylchroman-6-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-8-(6-methoxypyridin-3-yl)-2,2-dimethylchroman-6-carboxamide,

9-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4-methyl-2,5-dihydrobenzo[b]oxepine-7-carboxamide,

9-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-4-methyl-2,3,4,5-tetrahydrobenzo[b]oxepine-7-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-9-(6-methoxypyridin-3-yl)-4-methyl-2,3,4,5-tetrahydrobenzo[b]oxepine-7-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-2,3-dihydrobenzo[b]oxepine-7-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-2,3,4,5-tetrahydrobenzo[b]oxepine-7-carboxamide,

9-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-2,3,4,5-tetrahydrobenzo[b]oxepine-7-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-9-(4-(morpholinomethyl)phenyl)-2,3,4,5-tetrahydrobenzo[b]oxepine-7-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-9-(6-(piperazin-1-yl)pyridin-3-yl)-2,3,4,5-tetrahydrobenzo[b]oxepine-7-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-9-(6-methoxypyridin-3-yl)-2-methyl-2,3,4,5-tetrahydrobenzo[b]oxepine-7-carboxamide,

9-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-2,3,4,5-tetrahydrobenzo[b]oxepine-7-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3-methyl-9-(6-(piperazin-1-yl)pyridin-3-yl)-2,3,4,5-tetrahydrobenzo[b]oxepine-7-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-methoxypyridin-3-yl)-2-methyl-2-vinyl-2,3-dihydrobenzofuran-5-carboxamide,

7-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-2-vinyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-7-(4-(morpholinomethyl)phenyl)-2-vinyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-7-(6-(piperazin-1-yl)pyridin-3-yl)-2-vinyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-ethyl-7-(6-methoxypyridin-3-yl)-2-methyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-ethyl-2-methyl-7-(6-(piperazin-1-yl)pyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-ethyl-2-methyl-7-(p-tolyl)-2,3-dihydrobenzofuran-5-carboxamide,

rac-(3aS,8bS)-5-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3a-methyl-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-7-carboxamide,

rac-(3aS,8bS)—N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3a-methyl-5-(6-(piperazin-1-yl)pyridin-3-yl)-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-7-carboxamide,

rac-(3aS,8bS)—N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(6-methoxypyridin-3-yl)-3a-methyl-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-7-carboxamide,

rac-(3aS,8bS)—N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3a-methyl-5-(4-(piperidin-1-ylmethyl)phenyl)-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-7-carboxamide,

rac-(3aS,8bS)—N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3a-methyl-5-(4-(piperazin-1-yl)phenyl)-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-7-carboxamide,

rac-(3aS,8bS)-5-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3a,6-dimethyl-2,3,3a,8b-tetrahydro-1H-cyclopenta[b]benzofuran-7-carboxamide,

7-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3H-spiro[benzofuran-2,1′-cyclopentane]-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-methoxypyridin-3-yl)-3H-spiro[benzofuran-2,1′-cyclopentane]-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-(piperazin-1-yl)pyridin-3-yl)-3H-spiro[benzofuran-2,1′-cyclopentane]-5-carboxamide,

tert-Butyl 4-(5-(5-(((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)carbamoyl)-3H-spiro[benzofuran-2,1′-cyclopentan]-7-yl)pyrimidin-2-yl)piperazine-1-carboxylate,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(4-(piperidin-1-ylmethyl)phenyl)-3H-spiro[benzofuran-2,1′-cyclopentane]-5-carboxamide,

7-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2H-spiro[benzofuran-3,1′-cyclopentane]-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-methoxypyridin-3-yl)-2H-spiro[benzofuran-3,1′-cyclopentane]-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-(piperazin-1-yl)pyridin-3-yl)-2H-spiro[benzofuran-3,1′-cyclopentane]-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(4-(piperidin-1-ylmethyl)phenyl)-2H-spiro[benzofuran-3,1′-cyclopentane]-5-carboxamide,

7-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-isopropyl-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-isopropyl-7-(6-(piperazin-1-yl)pyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide,

9-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dimethyl-2,5-dihydrobenzo[b]oxepine-7-carboxamide,

7-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-2-(prop-1-en-2-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-7-(6-methoxypyridin-3-yl)-2-methyl-2-(prop-1-en-2-yl)-2,3-dihydrobenzofuran-5-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-isopropyl-7-(6-methoxypyridin-3-yl)-2-methyl-2,3-dihydrobenzofuran-5-carboxamide, HCl,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methyl-7-(6-(piperazin-1-yl)pyridin-3-yl)-2-(prop-1-en-2-yl)-2,3-dihydrobenzofuran-5-carboxamide, 2 TFA,

9-Bromo-3,4-dimethyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-2,5-dihydrobenzo[b]oxepine-7-carboxamide,

2-Methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-7-(6-(piperazin-1-yl)pyridin-3-yl)-2-(prop-1-en-2-yl)-2,3-dihydrobenzofuran-5-carboxamide, 2 TFA,

2-isopropyl-2-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl) methyl)-7-(6-(piperazin-1-yl)pyridin-3-yl)-2,3-dihydrobenzofuran-5-carboxamide, 2 HCl,

9-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-3,4-dimethyl-2,5-dihydrobenzo[b]oxepine-7-carboxamide,

8-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-vinyl-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide,

8-Bromo-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-ethyl-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide,

N-((4,6-Dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-ethyl-8-(6-(piperazin-1-yl)pyridin-3-yl)-2,3-dihydrobenzo[b][1,4]dioxine-6-carboxamide, 2 TFA,

2-Isopropyl-7-(6-(4-isopropylpiperazin-1-yl)pyridin-3-yl)-2-methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-2,3-dihydrobenzofuran-5-carboxamide,

2-Methyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-7-(2-(piperazin-1-yl)pyrimidin-5-yl)-2-(prop-1-en-2-yl)-2,3-dihydrobenzofuran-5-carboxamide, 2 HCl,

or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof.

6. A pharmaceutical composition comprising one or more compounds according to claim 1 and a pharmaceutically acceptable carrier or diluent.

7. A compound according to claim 1 for use in therapy.

Continuity (2)

Provisional Application 61907527 · Nov 22, 2013

Related Publication 20160297805A1 · Oct 13, 2016