Pyrazolo[1,5a]pyrimidine derivatives as IRAK4 modulators

Patent metadata

Field	Value
Publication number	US-9255110-B2
Application number	US-201414243074-A
Country	US
Kind code	B2
Filing date	Apr 2, 2014
Priority date	Jul 13, 2010
Publication date	Feb 9, 2016
Grant date	Feb 9, 2016

Abstract

Compounds of the formula I or II:

wherein X, m, Ar, R 1 and R 2 are as defined herein. The subject compounds are useful for treatment of IRAK-mediated conditions.

First claim

What is claimed is:

1. A compound, wherein said compound is of formula Ia or IIa:

wherein:
R 4 is halo:
R 3 is: halo-C 1-4 alkyl; C 1-6 alkenyl; C 1-6 alkoxy; halo-C 1-6 alkoxy; hydroxy-C 1-6 alkyl; hydroxy-C 1-6 alkylamino; C 1-6 alkyl-amino; amino; amino-C 1-6 alkyl; aminocarbonyl; hydroxy-C 1-6 alkoxy; hydroxy-C 1-6 alkenyl; C 1-6 alkoxy-C 1-6 alkoxy; C 1-6 alkylsulfonyl; C 1-6 alkylsulfanyl; piperidinyl wherein the piperidinyl moiety is optionally substituted with hydroxy, amino, amino-C 1-6 alkyl, hydroxy-C 1-6 alkyl or aminocarbonyl; phenylaminocarbonyl; hydroxy-C 1-6 alkylamino; cyclohexyloxy wherein the cyclohexyl moiety thereof is optionally substituted with hydroxy, amino, amino-C 1-6 alkyl or hydroxy-C 1-6 alkyl; cyclopentyloxy wherein the cyclopentyl moiety thereof is optionally substituted with hydroxy, amino, amino-C 1-6 alkyl or hydroxy-C 1-6 alkyl; piperidinyloxy wherein the piperidinyl moiety thereof is optionally substituted with hydroxy, amino, amino-C 1-6 alkyl, hydroxy-C 1-6 alkyl or aminocarbonyl; phenyl wherein the phenyl moiety is optionally substituted with amino, hydroxy, amino-C 1-6 alkyl, hydroxy-C 1-6 alkyl or aminocarbonyl; pyrrolidinyl wherein the pyrrolidinyl moiety is optionally substituted with hydroxy, amino, amino-C 1-6 alkyl, hydroxy-C 1-6 alkyl or aminocarbonyl; pyrrolidinyloxy wherein the pyrrolidinyl moiety is optionally substituted with hydroxy, amino, amino-C 1-6 alkyl, hydroxy-C 1-6 alkyl or aminocarbonyl; piperazinyl wherein the piperazinyl moiety is optionally substituted with C 1-6 alkyl; oxazol-C 1-6 alkoxy wherein the oxazol moiety thereof is optionally substituted with C 1-6 alkyl; morpholinyl; hydroxy-C 1-6 alkylaminocarbonyl; C 3-6 cycloalkyl; azepanyl wherein the azepanyl moiety is optionally substituted with hydroxy, amino, amino-C 1-6 alkyl, hydroxy-C 1-6 alkyl or aminocarbonyl; benzyl wherein the phenyl moiety thereof is optionally substituted with amino, hydroxy, amino-C 1-6 alkyl, hydroxy-C 1-6 alkyl or aminocarbonyl; C 1-6 alkoxycarbonyl-C 1-6 alkoxy; or C 1-6 alkylcabonylamino; and
R 1 is: hydrogen, C 1-6 alkyl, C 1-6 alkoxy, hydroxy, hydroxy-C 1-6 alkyl, C 1-6 alkyl-amino, amino-C 1-6 alkyl amino-C 1-6 alkyl-amino, hydroxy-C 1-6 alkylamino, C 3-6 cycloalkylamino, aminocarbonyl, halo, hydroxy-C 1-6 alkyl or hydroxy-C 1-6 alkoxy,

or a pharmaceutically acceptable salt thereof.

2. A composition comprising:
(a) a pharmaceutically acceptable carrier; and
(b) the compound of claim 1 .

3. A method for treating arthritis, said method comprising administering to a subject in need thereof an effective amount of the compound of claim 1 .

4. A method for treating a respiratory disorder selected from chronic obstructive pulmonary disorder (COPD), asthma, and bronchospasm, said method comprising administering to a subject in need thereof an effective amount of the compound of claim 1 .

5. A method for treating a disease or condition mediated by or otherwise associated with an IRAK receptor, the method comprising administering to a subject in need thereof an effective amount of the compound of claim 1 .

6. A method for treating a disease or condition mediated by or otherwise associated with an SYK receptor, the method comprising administering to a subject in need thereof an effective amount of the compound of claim 1 .

Assignees

• Hoffmann La Roche
• Roche Palo Alto Llc

Inventors

• Arora Nidhi
• Chen Shaoqing
• Hermann Johannes Cornelius
• Kuglstatter Andreas
• Labadie Sharada Shenvi
• Lin Clara Jeou Jen
• Lucas Matthew C
• Moore Amy Geraldine
• Papp Eva
• Talamas Francisco Xavier
• Wanner Jutta
• Zhai Yansheng

Classifications

• A61P37/08

  Antiallergic agents (antiasthmatic agents A61P11/06; ophthalmic antiallergics A61P27/14) · CPC title

• A61P37/06

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

• A61P43/00

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

• A61P37/02

  Immunomodulators · CPC title

• A61P31/04

  Antibacterial agents · CPC title