Aryl and heteroaryl fused lactams

Patent metadata

Field	Value
Publication number	US-2017233368-A1
Application number	US-201715585880-A
Country	US
Kind code	A1
Filing date	May 3, 2017
Priority date	Dec 21, 2012
Publication date	Aug 17, 2017
Grant date	—

Abstract

This invention relates to compounds of general formula (I)

in which R 1 , R 2 , U, V, L, M, R 5 , m, X, Y and Z are as defined herein, and the pharmaceutically acceptable salts thereof, to pharmaceutical compositions comprising such compounds and salts, and to methods of using such compounds, salts and compositions for the treatment of abnormal cell growth, including cancer.

First claim

1 - 7 . (canceled)

8 . A compound of formula (II-A):

or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is C 1 -C 4 alkyl or halo;
R 2 is 5-12 membered heteroaryl, where said 5-12 membered heteroaryl is optionally substituted by one or more R 32 ;
R 3 is H;
R 4 is H or halo;
m is 0;
R 5 is absent;
each R 32 is independently selected from the group consisting of —Cl, —F, —OH, —CH 3 , —CH 2 CH 3 , —CF 3 , —CH 2 OH, —CH 2 OCH 3 , —OCH 3 , —OC 2 H 5 , —OCF 3 , —CN, —C(O)NH 2 , —C(O)NHCH 3 , —C(O)N(CH 3 ) 2 , —NHC(O)CH 3 , —NH 2 , —NHCH 3 , —N(CH 3 ) 2 , cyclopropyl, 4-6 membered heterocyclyl, phenyl and 5-6 membered heteroaryl, where said 4-6 membered heterocyclyl, phenyl or 5-6 membered heteroaryl are optionally substituted by 1 to 3 halo, C 1 -C 4 alkyl or C 1 -C 4 alkoxy, which are independently selected;
X and Z are independently C 1 -C 4 alkyl or C 1 -C 4 alkoxy; and
Y is H.

9 . The compound or salt of claim 8 , wherein R 1 is chloro.

10 . The compound or salt of claim 8 , wherein R 2 is 5-12 membered heteroaryl selected from the group consisting of pyrazolyl, isoxazoyl and triazolyl, where said 5-12 membered heteroaryl is optionally substituted by 1 to 3 R 32 .

11 . The compound or salt of claim 10 , wherein each R 32 is independently selected from the group consisting of —CH 3 and —CH 2 CH 3 .

12 - 13 . (canceled)

14 . The compound or salt of claim 8 , wherein R 4 is halo.

15 - 16 . (canceled)

17 . A pharmaceutical composition comprising a compound of claim 8 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

18 . A method for the treatment of abnormal cell growth in a subject, comprising administering to the subject a therapeutically effective amount of a compound of claim 8 , or a pharmaceutically acceptable salt thereof.

19 . The method of claim 18 , wherein the abnormal cell growth is cancer.

20 . The method of claim 18 , wherein the subject is human.

21 . A compound that is 5-bromo-8-chloro-2-[(4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl]-7-(1,4-dimethyl-1H-1,2,3-triazol-5-yl)-3,4-dihydroisoquinolin-1(2H)-one, or a pharmaceutically acceptable salt thereof.

22 . A pharmaceutical composition comprising a compound of claim 21 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

Assignees

• Pfizer

Inventors

• Edwards Martin Paul
• Kumpf Robert Arnold
• Kung Pei-Pei
• McAlpine lndrawan James
• Ninkovic Sacha
• Rui Eugene Yuanjin
• Sutton Scott Channing
• Tatlock John Howard
• Wythes Martin James
• Zehnder Luke Raymond

Classifications

• A61P35/04

  specific for metastasis · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• C07D413/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title