Evaluation of WO2014075392 and WO2014075393, Merck’s first PI3Kδ inhibitor filings

Abstract

Introduction: There is considerable interest in the development of selective PI3Kδ inhibitors for the treatment of inflammatory diseases and haematological cancers. Merck has no previous filings in this field but licensed Exelixis' programme, including its lead compound XL-499, in December 2011.

Areas covered: Both applications claim novel 9-alkyl-6,8-disubstituted purine derivatives as selective δ inhibitors for the treatment of asthma, obstructive airways disease, arthritis and cancer. The two applications differ in the range of exemplified substituents, the first focusing on 8-heteroaryl substituted purines, the second on 8-aminopurine derivatives. Many of the exemplified compounds have IC50 values < 10 nM against PI3Kδ with a number having sub-nanomolar potency.

Expert Opinion: The compounds appear to be XL-499 derivatives, some of which are more potent than XL-499. The compounds claimed by Merck are some of the most potent PI3Kδ inhibitors yet described but it is unclear whether a development compound has been identified.

Keywords::

• asthma
• idelalisib
• lymphoma
• phosphatidylinositol 3-kinase delta inhibitor
• rheumatoid arthritis
• XL-499

Notes