Heteroaryl substituted pyrazoles

Patent metadata

Field	Value
Publication number	US-9745285-B2
Application number	US-201414900548-A
Country	US
Kind code	B2
Filing date	Jun 17, 2014
Priority date	Jun 21, 2013
Publication date	Aug 29, 2017
Grant date	Aug 29, 2017

Abstract

Compounds of formula (I), which are inhibitors of Bub1 kinase, processes for their production and their use as pharmaceuticals.

First claim

The invention claimed is:

1. A compound of formula (I)

wherein:
T is CH or CR 17 ;
Y is CH or CR 17 ;
R 2 is heteroaryl optionally substituted independently one or more times with hydroxy, halogen, cyano, or 1-3C-alkyl;
R 3 is hydrogen;
R 4 is
(a) hydrogen,
(b) hydroxy,
(c) 1-4C-alkoxy optionally substituted with
(c1) hydroxy,
(c3) —S—R 14 ,
(c4) —S(O)—R 14 ,
(c5) —S(O) 2 —R 14 , or
(c6) —S(═O)(═NR 15 )R 14 ,

(f) cyano, or
(g) —S(O) 2 -(1-4C-alkyl);

R 5 is hydrogen;
R 6 is halogen, cyano, —C(O)NR 11 R 12 , or —C(O)OR 13 ;
R 7 is 1-3C-alkyl or 3-6C-cycloalkyl;
R 8 is 1-3C-alkyl;
m is 0 or 1;
R 11 and R 12 are independently from each other hydrogen or 1-3C-alkyl;
R 13 is hydrogen or 1-3C-alkyl;
R 14 is methyl or cyclopropyl;
R 15 is hydrogen; and
R 17 is independently from each other halogen, cyano, —C(O)NR 11 R 12 or —C(O)OR 13 ,

or an N-oxide, a salt, a tautomer or a stereoisomer thereof, or a salt of said N-oxide, tautomer or stereoisomer.

2. The compound of formula (I) according to claim 1 , wherein:
T is CH;
Y is CH;
R 2 is heteroaryl optionally substituted independently one or more times with chloro or methyl;
R 3 is hydrogen;
R 4 is methoxy;
R 5 is hydrogen;
R 6 is —C(O)NR 11 R 12 or —C(O)OR 13 ;
R 7 is cyclopropyl;
R 8 is methyl;
m is 0 or 1;
R 11 and R 12 are each hydrogen; and
R 13 is hydrogen or ethyl,

or an N-oxide, a salt, a tautomer or a stereoisomer thereof, or a salt of said N-oxide, tautomer or stereoisomer.

3. The compound of formula (I) according to claim 1 , which is selected from the group consisting of:
2-{1-[(4-chloro-1-methyl-1H-pyrazol-5-yl)methyl]-5-cyclopropyl-4-methyl-1H-pyrazol-3-yl}-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amine;
4-[(2-{5-cyclopropyl-1-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]-4-methyl-1H-pyrazol-3-yl}-5-methoxypyrimidin-4-yl)amino]nicotinamide;
4-[(2-{5-cyclopropyl-1-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]-4-methyl-1H-pyrazol-3-yl}-5-methoxypyrimidin-4-yl)amino]nicotinic acid;
4-[(2-{5-cyclopropyl-1-[(3,5-dimethyl-1,2-oxazol-4-yl)methyl]-4-methyl-1H-pyrazol-3-yl}-5-methoxypyrimidin-4-yl)amino]nicotinate;
ethyl 4-[(2-{5-cyclopropyl-4-methyl-1-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]-1H-pyrazol-3-yl}-5-methoxypyrimidin-4-yl)amino]pyridine-3-carboxylate; and
4-[(2-{5-cyclopropyl-4-methyl-1-[(5-methyl-1,3,4-oxadiazol-2-yl)methyl]-1H-pyrazol-3-yl}-5-methoxypyrimidin-4-yl)amino]pyridine-3-carboxamide,

or an N-oxide, a salt, a tautomer or a stereoisomer thereof, or a salt of said N-oxide, tautomer or stereoisomer.

4. A pharmaceutical composition comprising the compound of formula (I) according to claim 1 , or an N-oxide, a salt, a tautomer or a stereoisomer thereof, or a salt of said N-oxide, tautomer or stereoisomer, together with at least one pharmaceutically acceptable carrier or auxiliary.

5. A combination comprising the compound of formula (I) according to claim 1 , or an N-oxide, a salt, a tautomer or a stereoisomer thereof, or a salt of said N-oxide, tautomer or stereoisomer, and an additional active ingredient selected from chemotherapeutic anti-cancer agents and target-specific anti-cancer agents.

Assignees

• Bayer Pharma AG

Inventors

• Mengel Anne
• Hitchcock Marion
• Richter Anja
• Bärfacker Lars
• Briem Hans
• Siemeister Gerhard
• Bone Wilhelm
• Fernandez-Montalvan Amaury Ernesto
• SCHRÖDER Jens
• Holton Simon
• Preuβe Cornelia
• Mönning Ursula

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

• A61P35/04

  specific for metastasis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D401/14 Primary

  containing three or more hetero rings · CPC title