Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Mar 15;27(6):1056-1064.
doi: 10.1016/j.bmc.2019.02.001. Epub 2019 Feb 1.

Optimization of 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidines to generate a highly selective PI3Kδ inhibitor

Toshihiro Hamajima  1 , Fumie Takahashi  2 , Koji Kato  2 , Yukihito Sugano  2 , Susumu Yamaki  2 , Daisuke Suzuki  2 , Ayako Moritomo  2 , Satoshi Kubo  2 , Koji Nakamura  2 , Kaoru Yamagami  2 , Koji Yokoo  2 , Hidehiko Fukahori  2
Affiliations

Optimization of 5,6,7,8-tetrahydropyrido[4,3-d]pyrimidines to generate a highly selective PI3Kδ inhibitor

Toshihiro Hamajima et al. Bioorg Med Chem. .

Abstract

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 PI3Kδ 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.

Keywords: 5,6,7,8-Tetrahydropyrido[4,3-d]pyrimidine; Isoform selectivity; PI3Kδ inhibitor.

PubMed Disclaimer

MeSH terms

Substances

LinkOut - more resources