Modification of a dihydropyrrolopyrimidine phosphoinositide 3-kinase (PI3K) inhibitor to improve oral bioavailability

Kawada Hatsuo; Ebiike Hirosato; Tsukazaki MasaoYamamoto ShunKoyama KoheiNakamura MitsuakiMorikami KenjiYoshinari KiyoshiYoshida MiyukiOgawa KotaroShinma NobuoTsukuda TakuoOhwada Jun

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Modification of a dihydropyrrolopyrimidine phosphoinositide 3-kinase (PI3K) inhibitor to improve oral bioavailability

机译：Modification of a dihydropyrrolopyrimidine phosphoinositide 3-kinase (PI3K) inhibitor to improve oral bioavailability

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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. (c) 2015 Elsevier Ltd. All rights reserved.

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《Bioorganic and medicinal chemistry》 |2015年第24期|7650-7660|共11页
作者
Kawada Hatsuo; Ebiike Hirosato; Tsukazaki MasaoYamamoto ShunKoyama KoheiNakamura MitsuakiMorikami KenjiYoshinari KiyoshiYoshida MiyukiOgawa KotaroShinma NobuoTsukuda TakuoOhwada Jun;
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作者单位

Chugai Pharmaceut Co Ltd, Div Res, Gotemba, Shizuoka 4128513, Japan;

Chugai Pharmaceut Co Ltd, Div Res, Kamakura, Kanagawa 2478530, Japan;

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正文语种英语
中图分类药学;
关键词
PI3K; Cancer; Solubility; Liver microsomal stability; Permeability; Molecular planarity; Pharmacokinetic profile;

Modification of a dihydropyrrolopyrimidine phosphoinositide 3-kinase (PI3K) inhibitor to improve oral bioavailability

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