2,3-disubstituted pyridine compounds as TGF-beta inhibitors and methods of use

Patent metadata

Field	Value
Publication number	US-10233170-B2
Application number	US-201515128051-A
Country	US
Kind code	B2
Filing date	Apr 2, 2015
Priority date	Apr 8, 2014
Publication date	Mar 19, 2019
Grant date	Mar 19, 2019

Abstract

The invention described herein comprises compounds of formula (IV) and a method of treating cancer comprising administering to a subject having cancer one of the compounds in conjunction with another therapeutic treatment of cancer. The compounds (IV) inhibit signaling by a member of the TGF-β superfamily such as Nodal or Activin.

First claim

We claim:

1. A compound of formula (IV):

or a pharmaceutically acceptable salt thereof, wherein
Cy 1 is phenyl substituted with 2, 3, or 4 moieties independently selected from halo, C 1-3 alkyl optionally substituted with 1, 2, or 3 halo, ethynyl, or (trimethylsilyl)ethynyl, and —O—C 1-3 alkyl optionally substituted with 1-3 halo; benzofuranyl; 2,3-dihydrobenzofuranyl; or phenylethenyl; or Cy 1 is phenyl substituted with a single substituent selected from halo, C 1-3 alkyl optionally substituted with 1, 2, or 3 halo, ethynyl, or (trimethylsilyl)ethynyl, —O—C 1-3 alkyl optionally substituted with 1-3 halo, —O—(C 0-3 alkyl)R IIIe , and —C(O)N(R x ) 2 ,
wherein R IIIe is phenyl, heteroaryl or heterocycloalkyl and each R x is independently H or C 1-3 alkyl;

Cy 2 is pyrazolo[1,5-a]pyrimidinyl; benzo[d]thiazolyl; imidazo[1,2-a]pyridinyl optionally substituted with phenyl-S(O) 2 —; [1,2,4]triazolo[1,5-a]pyridinyl; pyridinyl; quinazolinyl; 1H-pyrrolo[2,3-b]pyridinyl; pyrido[3,2-d]pyrimidinyl optionally substituted with amino, methylamino, or methoxy; or pyrido[3,2-d]pyrimidin-4(3H)-one,
wherein the quinazolinyl is optionally substituted with 1 or 2 substituents independently selected from —N(R IIIa ) 2 ; R IIId ; C 1-3 alkyl optionally substituted with 1-3 halo; halo; methoxy; and —N(H)(C 1-3 alkyl)R IV
each R IIIa is independently H; C 1-6 alkyl optionally substituted with —C(O)OH, —C(O)O(C 1-3 alkyl), or —CONH 2 ; or heteroaryl optionally substituted with C 1-3 alkyl;
R IIId is H or C 1-3 alkyl optionally substituted with 1-3 halo;
R IV is H, C 1-3 alkyl, -pyrrolidonyl, 4-methylpiperzinyl, —N(C 1-2 alkyl)(C 1-2 alkyl), or morpholinyl;

and
R IIIc is H, halo, —OH, C 1-3 alkyl optionally substituted with 1-3 halo, or —O—C 1-3 alkyl optionally substituted with 1-3 halo

provided the compound is not one of compounds 1-974:

Assignees

• Rigel Pharmaceuticals Inc

Inventors

• Singh Rajinder
• Bhamidipati Somasekhar
• Ding Pingyu
• Payan Donald
• Gelman Marina
• Kinsella Todd

Classifications

• A61P43/00

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

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/4439

  containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) · CPC title

• C07D417/14

  containing three or more hetero rings · CPC title