Benzimidazole derivatives as PI3 kinase inhibitors

Patent metadata

Field	Value
Publication number	US-10660898-B2
Application number	US-201916393210-A
Country	US
Kind code	B2
Filing date	Apr 24, 2019
Priority date	Oct 6, 2010
Publication date	May 26, 2020
Grant date	May 26, 2020

Abstract

This invention relates to the use of benzimidazole 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 benzimidazoles 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 benzimidazoles compounds for treating cancer.

First claim

What is claimed is:

1. A method for treating a susceptible PTEN-deficient neoplasm selected from prostate cancer, non-small-cell lung cancer, endometrial cancer, gastric cancer, melanoma, head and neck cancer, breast cancer and a glioma in a human in need thereof comprising the steps of:
(a) analyzing a sample from said neoplasm to determine whether there is a PTEN deficiency in cells of said neoplasm;
(b) selecting a human having said neoplasm with PTEN deficiency; and
(c) administering to the human a therapeutically effective amount the compound of formula

wherein
R 1 is selected from CO 2 Ra wherein Ra is C 1-3 alkyl;
R 2 is C 1-6 alkyl;
R 3 is phenyl substituted by C 1-3 alkyl and —CF 3 ; and,
R 4 is H,

or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein R 3 is

wherein
R 6 is C 1-3 alkyl; and
R 7 is —CF 3 .

3. The method of claim 1 , wherein R 3 is

4. The method of claim 1 , wherein R 1 is —CO 2 CH 3 and R 2 is —CH 3 .

Assignees

• Glaxosmithkline Llc

Inventors

• Tedesco Rosanna
• Qu Junya
• Sanchez Robert
• Rivero Ralph A

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• C07D401/10

  linked by a carbon chain containing aromatic rings · CPC title

• A61K31/5377 Primary

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• C07D413/04 Primary

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

• C07D405/10

  linked by a carbon chain containing aromatic rings · CPC title