Thiazolyl- or thiadiazolyl-substituted pyridyl compounds useful as kinase inhibitors

Patent metadata

Field	Value
Publication number	US-10227340-B2
Application number	US-201715818826-A
Country	US
Kind code	B2
Filing date	Nov 21, 2017
Priority date	Jan 13, 2012
Publication date	Mar 12, 2019
Grant date	Mar 12, 2019

Abstract

Compounds having the following formula:

or an enantiomer, diastereomer or a pharmaceutically-acceptable salt thereof, wherein X is N or C—R 7 , are useful as kinase modulators, including IRAK-4 modulation.

First claim

What is claimed is:

1. A compound having the following formula:

or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein
X is N;
R is C(═O)—R 1 , C(═O)O—R 1 or —C(═O)NR 11 —R 1 ;
R 1 is pyrrolidinyl substituted with 0-3 R 1a ;
R 1a is hydrogen, —OCF 3 , —CN, —(CH 2 ) r OR b , —(CH 2 ) r C(O)R b , —(CH 2 ) r C(O)OR b , —(CH 2 ) r OC(O)R b , —(CH 2 ) r NR 11 R 11 , —(CH 2 ) r C(O)NR 11 R 11 , —(CH 2 ) r NR b C(O)R c , —(CH 2 ) r NR b C(O)OR c , —S(O) p NR 11 R 11 , —NR b S(O) p R c , —S(O) 2 R c , or C 1-6 alkyl substituted with 0-2 R a ;
R 2 is benzo[d]thiazolyl;
R 3 is propyl substituted with 0-3 R 3a ;
R 3a is —OH or phenyl;
R 11 at each occurrence is hydrogen;
R a is R d , F, Cl, Br, —OCF 3 , —CF 3 , —CHF 2 , or —CN;
R b is R e , C 1-6 alkyl, or C 1-6 haloalkyl;
R c is —CH 3 ;
R d is hydrogen;
R e is hydrogen;
p is 0, 1, or 2; and
r is 0, 1, or 2.

2. The compound according to claim 1 or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 2 is:

3. The compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 3 is —CH(CH 3 ) 2 .

4. The compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 1 is pyrrolidinyl substituted with 0-2 R 1a .

5. The compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 1 is pyrrolidinyl substituted with 0-1 R 1a .

6. The compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein R 1a is H, —OH, —CH 2 OH, —NH 2 , —NHC(O)CH 3 , or NHS(O) 2 CH 3 .

7. The compound according to claim 1 , or a stereoisomer or pharmaceutically-acceptable salt thereof, wherein said compound is selected from
(5-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazol-2-yl)(2-(hydroxymethyl)pyrrolidin-1-yl)methanone (2);
(5-(6-(Benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazol-2-yl)(3-hydroxypyrrolidin-1-yl)methanone (5);
(5-(6-(Benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazol-2-yl)(3-hydroxypyrrolidin-1-yl)methanone (6);
(5-(6-(Benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazol-2-yl)(3-hydroxypyrrolidin-1-yl)methanone (7);
N-(1-(5-(6-(Benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazole-2-carbonyl)pyrrolidin-3-yl)acetamide (8);
(3-Aminopyrrolidin-1-yl)(5-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazol-2-yl)methanone (12);
N-(1-(5-(6-(Benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazole-2-carbonyl)pyrrolidin-3-yl)acetamide (13);
(3-Aminopyrrolidin-1-yl)(5-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazol-2-yl)methanone (14); and
N-(1-(5-(6-(Benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-1,3,4-thiadiazole-2-carbonyl)pyrrolidin-3-yl)methanesulfonamide (15).

8. A pharmaceutical composition comprising a compound according to claim 1 and a pharmaceutically acceptable carrier or diluent.

Assignees

• Bristol Myers Squibb Co

Inventors

• Paidi Venkatram Reddy
• Kumar Sreekantha Ratna
• Banerjee Abhisek
• Sistla Ramesh Kumar
• Nair Satheesh Kesavan
• Pitts William J
• Hynes John

Classifications

• A61P43/00

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

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P37/02

  Immunomodulators · CPC title

• A61P35/04

  specific for metastasis · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title