Azaquinazoline inhibitors of atypical protein kinase C

Patent metadata

Field	Value
Publication number	US-9896446-B2
Application number	US-201514975605-A
Country	US
Kind code	B2
Filing date	Dec 18, 2015
Priority date	Sep 28, 2012
Publication date	Feb 20, 2018
Grant date	Feb 20, 2018

Abstract

The present application provides a compound of formula (I)

or a salt thereof, wherein R 7 , R 8 , R 9 , G, and X are as defined herein. This application further describes compositions comprising the same. Compounds of formula (I) and their salts have aPKC inhibitory activity, and may be used to treat proliferative diseases.

First claim

The invention claimed is:

1. A compound selected from the group consisting of:
(5-Cyclobutyl-3-fluoro-pyridin-2-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;
{5-Cyclopropyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine;
(4-Chloro-1-ethyl-1H-pyrazol-3-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine;
[4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine;
{4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine; and
{4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(1-isopropyl-1H-pyrazol-3-yl)-amine;
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein the compound is (5-(Cyclobutyl-3-fluoro-pyridin-2-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein the compound is {5-Cyclopropyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein the compound is (4-Chloro-1-ethyl-1H-pyrazol-3-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 , wherein the compound is [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 , wherein the compound is {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , wherein the compound is {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(1-isopropyl-1H-pyrazol-3-yl)-amine or a pharmaceutically acceptable salt thereof.

8. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

9. The pharmaceutical composition of claim 8 , wherein the compound of claim 1 is (5-Cyclobutyl-3-fluoro-pyridin-2-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine or a pharmaceutically acceptable salt thereof.

10. The pharmaceutical composition of claim 8 , wherein the compound of claim 1 is {5-Cyclopropyl-2-[2-(3,5,6-trifluoro-pyridin-2-ylamino)-pyridin-4-yl]-pyrido[3,4-d]pyrimidin-4-yl}-methyl-piperidin-4-yl-amine or a pharmaceutically acceptable salt thereof.

11. The pharmaceutical composition of claim 8 , wherein the compound of claim 1 is (4-Chloro-1-ethyl-1H-pyrazol-3-yl)-[4-(5-cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-amine or a pharmaceutically acceptable salt thereof.

12. The pharmaceutical composition of claim 8 , wherein the compound of claim 1 is [4-(5-Cyclopropyl-4-piperazin-1-yl-pyrido[3,4-d]pyrimidin-2-yl)-pyridin-2-yl]-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine or a pharmaceutically acceptable salt thereof.

13. The pharmaceutical composition of claim 8 , wherein the compound of claim 1 is {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-[1-(2,2,2-trifluoro-ethyl)-1H-pyrazol-3-yl]-amine or a pharmaceutically acceptable salt thereof.

14. The pharmaceutical composition of claim 8 , wherein the compound of claim 1 is {4-[5-Cyclopropyl-4-(3,3-dimethyl-piperazin-1-yl)-pyrido[3,4-d]pyrimidin-2-yl]-pyridin-2-yl}-(1-isopropyl-1H-pyrazol-3-yl)-amine or a pharmaceutically acceptable salt thereof.

Assignees

• Ignyta Inc
• Cancer Research Tech Ltd

Inventors

• Breslin Henry J
• Dorsey Bruce D
• Dugan Benjamin J
• Hudkins Robert L
• Mesaros Eugen F
• Ott Gregory R
• Zificsak Craig A
• Zulli Allison L
• Tao Ming
• Fowler Katherine M
• Morris Emma L
• Pave Gregoire A
• Roffey Jonathan R A
• Monck Nathaniel J T
• Soudy Christelle N
• Olowoye Ikeoluwa

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

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

• C07D471/04 Primary

  Ortho-condensed systems · CPC title

• C07D493/08

  Bridged systems · CPC title

• C07D519/00

  Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00 · CPC title