Modification of a dihydropyrrolopyrimidine phosphoinositide 3-kinase (PI3K) inhibitor to improve oral bioavailability. Issue 24 (15th December 2015)

• Record Type: Journal Article
• Authors: Kawada, Hatsuo; Ebiike, Hirosato; Tsukazaki, Masao; Yamamoto, Shun; Koyama, Kohei; Nakamura, Mitsuaki; Morikami, Kenji; Yoshinari, Kiyoshi; Yoshida, Miyuki; Ogawa, Kotaro; Shinma, Nobuo; Tsukuda, Takuo; Ohwada, Jun
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 24(2015)
• Page Start: 7650
• Page End: 7660
• Publication Date: 2015-12-15
• Subjects: PI3K -- Cancer -- Solubility -- Liver microsomal stability -- Permeability -- Molecular planarity -- Pharmacokinetic profile; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.11.009
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Phosphoinositide 3-kinase (PI3K) is activated in various human cancer cells and well known as a cancer therapy target. We previously reported a dihydropyrrolopyrimidine derivative as a highly potent PI3K inhibitor that has strong tumor growth inhibition in a xenograft model. In this report, we describe further optimization to improve its bioavailability.