Identification of highly potent and selective PI3Kδ inhibitors

David Marcoux; Lan-Ying Qin; Zheming Ruan; Qing Shi; Qian Ruan; Carolyn Weigelt; Hongchen Qiu; Gary Schieven; John Hynes; Rajeev Bhide; Michael Poss; Joseph Tino

doi:10.1016/j.bmcl.2017.01.077

Identification of highly potent and selective PI3Kδ inhibitors

Bioorg Med Chem Lett. 2017 Jul 1;27(13):2849-2853. doi: 10.1016/j.bmcl.2017.01.077. Epub 2017 Feb 7.

Authors

Affiliations

¹ Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States. Electronic address: [email protected].
² Research & Development, Bristol-Myers Squibb Company, Route 206 & Province Line Road, Princeton, NJ 08543, United States.

PMID: 28209465
DOI: 10.1016/j.bmcl.2017.01.077

Abstract

Selective PI3Kδ inhibitors have recently been hypothesized to be appropriate immunosuppressive agents for the treatment of immunological disorders such as rheumatoid arthritis. However, few reports have highlighted molecules that are highly selective for PI3Kδ over the other PI3K isoforms. In this letter, isoform and kinome selective PI3Kδ inhibitors are presented. The Structural Activity Relationship leading to such molecules is outlined.

Keywords: Autoimmune diseases; PI3Kδ; Phosphoinositide 3-kinases; Pyrrolotriazine; Rheumatoid arthritis.

MeSH terms

Animals
Dose-Response Relationship, Drug
Humans
Mice
Models, Molecular
Molecular Structure
Phosphatidylinositol 3-Kinases / metabolism
Phosphoinositide-3 Kinase Inhibitors*
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / chemistry
Protein Kinase Inhibitors / pharmacology*
Structure-Activity Relationship

Substances

Phosphoinositide-3 Kinase Inhibitors
Protein Kinase Inhibitors