Amino-quinolines as kinase inhibitors

Patent metadata

Field	Value
Publication number	US-9604963-B2
Application number	US-201214002147-A
Country	US
Kind code	B2
Filing date	Mar 2, 2012
Priority date	Mar 4, 2011
Publication date	Mar 28, 2017
Grant date	Mar 28, 2017

Abstract

Disclosed are compounds having the formula:

wherein R 1 , R 2 , R 3 and Z are as defined herein, and methods of making and using the same.

First claim

What is claimed is:

1. A compound according to Formula (I):

wherein:
R 1 is H, —SO 2 (C 1 -C 4 alkyl), —CO(C 1 -C 4 alkyl), or (C 1 -C 4 alkyl);
R 2 is —SOR a or —SO 2 R a , wherein R a is an optionally substituted (C 1 -C 6 )alkyl, (C 3 -C 7 )cycloalkyl, 4-7membered heterocycloalkyl, aryl, or heteroaryl group, wherein:
said (C 1 -C 6 )alkyl is optionally substituted by one or two groups each independently selected from the group consisting of cyano, hydroxyl, (C 1 —C 6 )alkoxy, (C 1 -C 6 )alkoxy(C 2 -C 6 )alkoxy, —CO 2 H, —CO 2 (C 1 -C 4 )alkyl, —SO 2 (C 1 -C 4 alkyl), —CONH 2 , —CONH(C 1 -C 4 alkyl), —CON(C 1 -C 4 alkyl)(C 1 -C 4 alkyl), —SO 2 NH 2 , —SO 2 NH(C 1 -C 4 alkyl), —SO 2 N(C 1 -C 4 alkyl)(C 1 -C 4 alkyl), amino, (C 1 -C 4 alkyl)amino-, (C 1 -C 4 alkyl)(C 1 -C 4 alkyl)amino-, C 3 -C 7 cycloalkyl, phenyl, 5-6membered heteroaryl, 9-10membered heteroaryl, 4-7membered heterocycloalkyl and (phenyl)(C 1 -C 4 alkyl)amino-, wherein said C 3 -C 7 cycloalkyl, phenyl, (phenyl)(C 1 -C 4 alkyl)amino-, 5-6membered heteroaryl, 9-10membered heteroaryl or 4-7membered heterocycloalkyl is optionally substituted by 1-3groups each independently selected from the group consisting of halogen, —CF 3 , (C 1 -C 4 )alkyl, hydroxy(C 1 -C 4 )alkyl and (C 1 -C 4 )alkoxy,
said (C 3 -C 7 )cycloalkyl or 4-7membered heterocycloalkyl is optionally substituted by 1-3groups each independently selected from the group consisting of halogen, —CF 3 , hydroxyl, amino, (C 1 -C 4 )alkyl, phenyl(C 1 -C 4 )alkyl-, hydroxy(C 1 -C 4 )alkyl-, oxo, and (C 1 -C 4 )alkoxy, and
said aryl or heteroaryl is optionally substituted by 1-3 groups each independently selected from the group consisting of halogen, —CF 3 , hydroxyl, amino, (C 1 -C 4 )alkyl, phenyl(C 1 -C 4 )alkyl-, hydroxy(C 1 -C 4 )alkyl- and (C 1 -C 4 )alkoxy,
and wherein said heteroaryl is a 5-6 membered heteroaryl or a 9-10 membered heteroaryl, and any of said 4-7 membered heterocycloalkyl contains one heteroatom selected from the group consisting of N, O and S, any of said 5-6 membered heteroaryl contains one heteroatom selected from the group consisting of N, O and S and optionally further containing one or two nitrogen atoms, and any of said 9-10 membered heteroaryl contains one heteroatom selected from the group consisting of N, O and S and optionally further containing 1, 2 or 3 nitrogen atoms;
R 3 is halogen, hydroxy, (C 1 -C 4 )alkoxy-, halo(C 1 -C 4 )alkyl-, halo(C 1 -C 4 )alkoxy-, (C 1 -C 4 )alkoxy(C 1 -C 6 )alkyl-, halo(C 1 -C 4 )alkoxy(C 1 -C 6 )alkyl-, (C 1 -C 4 )alkoxy(C 2 -C 6 )alkoxy-, halo(C 1 -C 4 )alkoxy(C 2 -C 6 )alkoxy-, hydroxy(C 1 -C 4 )alkyl-, hydroxy(C 2 -C 6 )alkoxy-, cyano(C 1 -C 4 )alkyl-, cyano(C 2 -C 6 )alkoxy-, or (C 3 -C 6 )cycloalkoxy-, wherein the halo(C 1 -C 4 )alkyl-, halo(C 1 -C 4 )alkoxy-, halo(C 1 -C 4 )alkoxy(C 1 -C 6 )alkyl-, or halo(C 1 -C 4 )alkoxy(C 2 -C 6 )alkoxy- contains 2 or 3 halo atoms and wherein the (C 3 -C 6 )cycloalkyl moiety of the (C 3 -C 6 )cycloalkoxy- group, is optionally substituted by a group selected from the group consisting of cyano, halo, hydroxyl, (C 1 -C 6 )alkoxy and (C 1 -C 4 )alkoxy(C 2 -C 6 )alkoxy;
Z is pyrazolyl, having the formula:

 wherein:
R 12 is methyl or trifluoromethyl;
R 13 is H, methyl, or trifluoromethyl;
R 14 is H or (C 1 -C 3 )alkyl; or
R 12 and R 13 , taken together with the atoms to which they are attached, form a 6membered carbocyclic ring or heterocyclic ring substituted by R 15 and R 16 , wherein the heterocyclic ring contains 1 nitrogen atom;
wherein R 15 and R 16 are each independently selected from the group consisting of H, halogen, cyano, (C 1 -C 4 )alkyl, halo(C 1 -C 4 )alkyl, (C 1 -C 4 )alkoxy, phenoxy, phenyl(C 1 -C 4 )alkoxy, hydroxyl, hydroxy(C 1 -C 4 )alkyl-, and aminocarbonyl, wherein the phenyl moiety of said phenoxy or phenyl(C 1 -C 4 )alkoxy is optionally substituted by 1-3 substituents each independently selected from the group consisting of halogen, —CF 3 , (C 1 -C 4 )alkyl and (C 1 -C 4 )alkoxy;
or a salt thereof.

2. The compound or salt according to claim 1 , wherein R 1 is H.

3. The compound or salt according to claim 1 , wherein R 2 is -SO 2 R a .

4. The compound, or salt thereof, according to claim 1 , wherein the salt is a pharmaceutically acceptable salt of said compound.

5. A compound which is:

or a pharmaceutically acceptable salt thereof.

6. A pharmaceutical composition comprising the compound, or pharmaceutically acceptable salt thereof, according to claim 4 , and a pharmaceutically acceptable excipient.

7. A pharmaceutical composition comprising the compound, or pharmaceutically acceptable salt thereof, according to claim 5 , and a pharmaceutically acceptable excipient.

Assignees

• Bury Michael Jonathan
• Casillas Linda N
• Charnley Adam Kenneth
• Haile Pamela A
• Marquis Jr Robert W
• Mehlmann John F
• Romano Joseph J
• Singhaus Jr Robert R
• Wang Gren Z
• Glaxosmithkline Ip Dev Ltd

Inventors

• Bury Michael Jonathan
• Casillas Linda N
• Charnley Adam Kenneth
• Haile Pamela A
• Marquis Jr Robert W
• Mehlmann John F
• Romano Joseph J
• Singhaus Jr Robert R
• Wang Gren Z

Classifications

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/08

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

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · 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