Optimization Of 5,6,7,8-Tetrahydropyrido [4,3-D]Pyrimidines To Generate A Highly Selective Pi3k Delta Inhibitor

Chemical optimization of the 5,6,7,8-tetrahydropyrido[4,3-d] pyrimidine (THPP) scaffold was conducted with a focus on cellular potency while maintaining high selectivity against PI3K isoforms. Compound 11f was identified as a potent, highly selective and orally available PI3K delta inhibitor. In addition, 11f exhibited efficacy in an in vivo antibody production model. The desirable drug-like properties and in vivo efficacy of 11f suggest its potential as a drug candidate for the treatment of autoimmune diseases and leukocyte malignancies.