# US 8,541,411 B2 · Benzimidazole derivatives as PI3 kinase inhibitors

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- Number: US 8,541,411 B2
- Document ID: US8541411B2
- Status: Granted
- Kind: B2
- Application number: 13/798,923
- Filed: 2013-03-13
- Published: 2013-08-01
- Granted: 2013-09-24
- Earliest claimed: 2010-10-06
- Assignees: GlaxoSmithKline LLC
- Applicants: GlaxoSmithKline LLC
- Inventors: Junya Qu; Ralph A. Rivero; Robert Sanchez; Rosanna Tedesco
- Web page: https://patentgrep.com/patent/US8541411B2

## CPC

- A61K 31/5377: not condensed and containing further heterocyclic rings, e.g. timolol
- A61K 31/337: having four-membered rings, e.g. taxol
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- A61P 37/00: Drugs for immunological or allergic disorders
- C07D 235/08: Radicals containing only hydrogen and carbon atoms
- C07D 235/10: Radicals substituted by halogen atoms or nitro radicals
- C07D 235/24: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
- C07D 401/10: linked by a carbon chain containing aromatic rings
- C07D 403/04: directly linked by a ring-member-to-ring-member bond
- C07D 403/10: linked by a carbon chain containing aromatic rings
- C07D 405/04: directly linked by a ring-member-to-ring-member bond
- C07D 405/10: linked by a carbon chain containing aromatic rings
- C07D 409/10: linked by a carbon chain containing aromatic rings
- C07D 413/04: directly linked by a ring-member-to-ring-member bond
- C07D 413/10: linked by a carbon chain containing aromatic rings
- C07D 417/04: directly linked by a ring-member-to-ring-member bond
- C07D 417/10: linked by a carbon chain containing aromatic rings
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## 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.

## Claims

### Claim 1

A process for the preparation of the benzimidazole of formula (3) comprising the steps of
ester hydrolyzing the methyl ester of formula (2) with lithium hydroxide in THF/water,
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.