1007206-00-9Relevant academic research and scientific papers
Lead optimization of a dihydropyrrolopyrimidine inhibitor against phosphoinositide 3-kinase (PI3K) to improve the phenol glucuronic acid conjugation
Kawada, Hatsuo,Ebiike, Hirosato,Tsukazaki, Masao,Nakamura, Mitsuaki,Morikami, Kenji,Yoshinari, Kiyoshi,Yoshida, Miyuki,Ogawa, Kotaro,Shimma, Nobuo,Tsukuda, Takuo,Ohwada, Jun
, p. 673 - 678 (2013/02/23)
Our lead compound for a phosphoinositide 3-kinase (PI3K) inhibitor (1) was metabolically unstable because of rapid glucuronidation of the phenol moiety. Based on structure-activity relationship (SAR) information and a FlexSIS docking simulation score, aminopyrimidine was identified as a bioisostere of phenol. An X-ray structure study revealed a hydrogen bonding pattern of aminopyrimidine derivatives. Finally, aminopyrimidine derivatives 33 showed strong tumor growth inhibition against a KPL-4 breast cancer xenograft model in vivo.
