US 2013/0157977 A1 · Benzimidazole Boronic Acid Derivatives As PI3 Kinase Inhibitors

Abstract

This invention relates to the use of benzimidazole boronic acid derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3′ OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of benzimidazole boronic acids in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More suitably, the present invention relates to PI3Kβ selective benzimidazole boronic acid compounds for treating cancer.

Claims13

Dependent claims

A compound of formula (I):

wherein
R2 is selected from H, —NHRa, alkoxy, halogen, —CF3, —CHF2, and C1-6alkyl;
R3 is selected from aryl and heteroaryl, wherein said aryl or heteroaryl may be substituted by one to three Rc;
R4 is selected from H or Ra;
each R5 is independently selected from C1-6alkyl;
each Ra is independently selected from C1-3alkyl;
each Rc is independently selected from C1-3alkyl, halogen, —CF3, and hydroxy;
and
n is 0-2,
or a pharmaceutically acceptable salt thereof.

7 more elements

A compound selected from

4-(4-bromo-2-methyl-1H-benzo[d]imidazol-6-yl)morpholine;
4-(4-bromo-1-(3-chloro-2-methylbenzyl)-2-methyl-1H-benzo[d]imidazol-6-yl)morpholine;
4-(4-bromo-2-methyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-1H-benzo[d]imidazol-6-yl)morpholine;
(2-methyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(1-(3-chloro-2-methylbenzyl)-2-methyl-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(2-methyl-6-morpholino-1-(naphthalen-1-ylmethyl)-1H-benzo[d]imidazol-4-yl)boronic acid;
(1-(2,3-dimethylbenzyl)-2-methyl-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(1-(2,3-dichlorobenzyl)-2-methyl-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
4-(1-(benzo[b]thiophen-7-ylmethyl)-4-bromo-2-methyl-1H-benzo[d]imidazol-6-yl)morpholine;
(2-methyl-1-(3-methylbenzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(2-methyl-1-(2-methylbenzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(1-(2-chlorobenzyl)-2-methyl-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(1-(3-chlorobenzyl)-2-methyl-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(1-(3-chloro-2-methylbenzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(2-(fluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(1-(3-chloro-2-methylbenzyl)-2-(fluoromethyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(2-(hydroxymethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(1-(3-chloro-2-methylbenzyl)-2-(difluoromethyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(2-(difluoromethyl)-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
(1-(3-chloro-2-methylbenzyl)-6-morpholino-2-(trifluoromethyl)-1H-benzo[d]imidazol-4-yl)boronic acid;
(2-isopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid;
and
(2-cyclopropyl-1-(2-methyl-3-(trifluoromethyl)benzyl)-6-morpholino-1H-benzo[d]imidazol-4-yl)boronic acid,
or a pharmaceutically acceptable salt thereof.

22 more elements

Dependencies are inferred from the claim text.

Facts

Application

13/674,202Filed 12 Nov 2012

Priority

20 Dec 2011

Published

20 Jun 2013

Term ends

Not estimatedThe source records don’t support an estimate.

Classification4 codes

C07F 5/025
Boron compounds: boronic and borinic acid compounds
C07D 417/10
Containing two hetero rings: linked by a carbon chain containing aromatic rings
C07F
Acyclic, carbocyclic or heterocyclic compounds containing elements other than carbon, hydrogen, halogen
C07D
Heterocyclic compounds

Benzimidazole Boronic Acid Derivatives As PI3 Kinase Inhibitors

Life of this patent

Benzimidazole Boronic Acid Derivatives As PI3 Kinase Inhibitors

Life of this patent

Abstract

Claims13