Azaquinazoline inhibitors of Atypical protein Kinase C

Patent metadata

Field	Value
Publication number	US-9914730-B2
Application number	US-201314038915-A
Country	US
Kind code	B2
Filing date	Sep 27, 2013
Priority date	Sep 28, 2012
Publication date	Mar 13, 2018
Grant date	Mar 13, 2018

Abstract

The present application provides azaquinazoline compounds as defined herein. This application further describes compositions comprising the same. These azaquinazoline compounds and their salts have atypical protein kinase C (“aPKC”) inhibitory activity, and may be used to treat proliferative disorders.

First claim

The invention claimed is:

1. A compound of formula I:

wherein R 7 is an optionally substituted C 3 -C 6 cycloalkyl;
R 8 is hydrogen;
R 9 is hydrogen;
X is a 5-10 membered heterocycloalkyl containing 1 or 2 nitrogen atoms, wherein said heterocycloalkyl is optionally substituted with 1-4 hydroxyl or C 1 -C 3 alkyl;
G is

R 14 is hydrogen;
R 15 is hydrogen; and
R 12 and R 13 are independently hydrogen or an optionally substituted amino group; or
R 12 and R 13 , together with the atoms to which they are attached, form an optionally substituted 5 to 15 membered heteroaryl or an optionally substituted 3 to 15 membered heterocycloalkyl,
or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R 7 is cyclopropyl or cyclobutyl, or a pharmaceutically acceptable salt thereof.

3. The compound of claim 1 , wherein X is an optionally substituted piperazinyl, or a pharmaceutically acceptable salt thereof.

4. The compound of claim 1 , wherein X is an optionally substituted piperazinyl, wherein the piperazinyl is attached to the:

ring via a nitrogen atom, or a pharmaceutically acceptable salt thereof.

5. The compound of claim 1 , wherein X is an optionally substituted piperidinyl, or a pharmaceutically acceptable salt thereof.

6. The compound of claim 1 , wherein X is an optionally substituted piperidinyl, wherein the piperidinyl is attached to the:

ring via a nitrogen atom, or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , wherein R 12 and R 13 , together with the atoms to which they are attached, form an optionally substituted 5 to 15 membered heteroaryl, or a pharmaceutically acceptable salt thereof.

8. The compound of claim 7 , wherein said optionally substituted 5 to 15 membered heteroaryl contains at least one nitrogen atom, or a pharmaceutically acceptable salt thereof.

9. The compound of claim 1 , wherein R 12 and R 13 , together with the atoms to which they are attached, form an optionally substituted 3 to 10 membered heterocycloalkyl, or a pharmaceutically acceptable salt thereof.

10. The compound of claim 9 , wherein said optionally substituted 3 to 10 membered heterocycloalkyl contains at least one nitrogen atom, or a pharmaceutically acceptable salt thereof.

11. A compound selected from the group consisting of:

or a pharmaceutically acceptable salt thereof.

12. A pharmaceutical composition comprising one or more compounds according to claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

13. A pharmaceutical composition comprising one or more compounds according to claim 11 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

Assignees

• Ignyta Inc
• Cancer Research Tech Ltd

Inventors

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

Classifications

• A61P43/00

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

• A61P35/00

  Antineoplastic agents · 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