Pyridinones

Patent metadata

Field	Value
Publication number	US-9296748-B2
Application number	US-201514714521-A
Country	US
Kind code	B2
Filing date	May 18, 2015
Priority date	Aug 14, 2013
Publication date	Mar 29, 2016
Grant date	Mar 29, 2016

Abstract

The present invention encompasses compounds of general formula (I)

wherein the groups R 1 to R 3 and X 1 through X 6 have the meanings given in the claims and in the specification. The compounds of the invention are suitable for the treatment of diseases characterized by excessive or abnormal cell proliferation pharmaceutical preparations containing such compounds and their uses as a medicament.

First claim

The invention claimed is:

1. A compound of the formula (I)

wherein,
R 1 is —C 1-3 alkyl and R 2 is selected from —C 1-3 alkyl, —C 1-3 haloalkyl, —NH 2 , —NH—C 1-3 alkyl, and halogen;
R 3 is —C 1-4 alkyl substituted with one or more groups independently selected from halogen, —C 1-2 haloalkyl, —O—C 1-3 alkyl, —O—C 1-3 haloalkyl, 4-7 membered heterocycloalkyl, —C 3-7 cycloalkyl, phenyl and 5-6 membered heteroaryl, wherein the phenyl and the 5-6 membered heteroaryl groups can be optionally substituted with one or more groups independently selected from halogen and —C 1-2 alkyl;
X 1 is —CH═ or —N═
X 2 is —CR 7 ═ or —N═,
wherein X 1 is —CH═ and X 2 is —N═, or X 1 is —N═ and X 2 is —CH═, or X 1 is —CH═ and X 2 is ═CR 7 ═
X 3 is —CR 8 ═ or —N═;
X 4 is —CR 4 ═ or —N═;
X 5 is —CR 5 ═ or —N═;
X 6 is —CH═ or —N═;
with the proviso that none or only one or two among X 3 , X 4 , X 5 and X 6 are —N═;
R 4 is selected from —H, halogen, —CN, —NH 2 , —O—R 6 , —N(C 1-3 alkyl) 2 , —C(O)N(C 1-3 alkyl) 2 and —C 1-5 alkyl, wherein the —C 1-5 alkyl group can be optionally and independently substituted with one or more groups independently selected from halogen or —CN, or
R 4 is selected from 5-6 membered heteroaryl and 4-7 memebered heterocycloalkyl, wherein the heteroaryl groups can be optionally and independently substituted with one or more groups independently selected from —C 1-3 alkyl, and the heterocycloalkyl group can be optionally and independently substituted with one or more groups independently selected from —C 1-3 alkyl or ═ O, or
R 4 is a —C 3-6 cycloalkyl wherein the cycloalkyl group can be optionally and independently substituted with one or more groups independently selected from C 1-3 alkyl, —C 1-3 haloalkyl and halogen;
R 5 is selected from —H, halogen, —NH 2 , —C 1-3 alkyl, —SO 2 N(C 1-3 alkyl) 2 and 5-6 membered heterocycloalkyl, which heterocycloalkyl can be optionally substituted with one or more groups independently selected from ═O, —C 1-3 alkyl, and —C 1-5 haloalkyl;
R 6 is selected from 4-7 membered heterocycloalkyl, —C 3-7 cycloalkyl and —C 1-5 alkyl, wherein the —C 1-5 alkyl group can be optionally substituted with —C 3-7 cycloalkyl ,
R 7 is selected from —H, —C 1-5 alkyl and —O—C 1-5 alkyl;
R 8 is —H or —C 1-3 alkyl;
or a pharmaceutically acceptable salt thereof.

2. A compound according to claim 1 , of a formula selected from the group consisting of.

3. A compound according to claim 2 , of a formula selected from the group consisting of.

4. A compound according to claim 1 , of the formula.

5. A compound according to claim 1 , wherein R 1 is —CH 3 .

6. A compound according to claim 1 , wherein R 2 is —NH 2 , —NH—C 1-3 alkyl or —C 1-3 alkyl.

7. A compound according to claim 6 , wherein R 2 is —NH 2 , —NHCH 3 or —CH 3 .

8. A compound according to claim 7 , wherein R 2 is —CH 3 .

9. A compound according to claim 1 , wherein wherein R 3 is —CH(CH 3 )—CH 2 —O—CH 3 , —CH(CH 3 )—CH 2 -cyclopropyl, —CH 2 -phenyl, —CH 2 -pyridyl, —CH(CH 3 )phenyl, or —CH(CH 3 )-pyridyl, wherein the phenyl and pyridyl groups are optionally and independently substituted with —Cl or with one or two —F.

10. A compound according to claim 9 , wherein R 3 is —CH 2 -phenyl, —CH 2 -pyridyl, —CH(CH 3 )phenyl or —CH(CH 3 )-pyridyl.

11. A compound according to claim 10 , wherein R 3 is —CH 2 -phenyl or —CH(CH 3 )phenyl.

12. A compound according to claim 1 , wherein R 4 is —H, halogen, —CN, —NH 2 , —C 1-5 alkyl, —N(C 1-3 alkyl) 2 , —C(O)N(C 1-3 alkyl) 2 , —O—C 1-5 alkyl, —O—CH 2 -cyclopropyl, —O—(6 membered heterocycloalkyl), —O—cyclopropyl, 5-6 membered heteroaryl or 4-7 memebered heterocycloalkyl, wherein the heterocycloalkyl is optionally substituted with one or more groups independently selected from —C 1-3 alkyl.

13. A compound according to claim 12 , wherein R 4 is selected from —H, —F, —Cl, —CN, isopropyl, —NH 2 , —N(CH 3 ) 2 , —C(O)N(CH 3 ) 2 , —O—CH 3 , —O—(CH 2 ) 2 CH 3 , —O-piperidine, —O-cyclopropyl, —O—CH 2 -cyclopropyl, imidazole, tetrahydropyran, piperazine substituted with —CH 3 , and morpholine optionally substituted with —CH 3 .

14. A compound according to claims 12 , wherein R 4 is selected from —C 1-5 alkyl or 4-7 memebered heterocycloalkyl, which heterocycloalkyl can be optionally substituted with one or more groups independently selected from —C 1-3 alkyl.

15. A compound according to claim 14 , wherein R 4 is selected from isopropyl, tetrahydropyran, piperazine substituted with —CH 3 and morpholine optionally substituted with —CH 3 .

16. A compound according to claim 1 , wherein R 5 is selected from —H, —Cl, —NH 2 , —SO 2 N(CH 3 ), piperazine optionally substituted with —CH 3 , tetrahydropyran and

17. A compound according to claim 1 selected from the group consisting of

EX#
Structure

I-1

I-6

I-9

I-10

I-11

I-12

Assignees

• Boehringer Ingelheim Int

Inventors

• Engelhardt Harald
• Martin Laetitia
• Smethurst Christian

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P43/00

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

• A61P35/00

  Antineoplastic agents · CPC title

• C07D403/14

  containing three or more hetero rings · CPC title

• C07D401/04

  directly linked by a ring-member-to-ring-member bond · CPC title