Discovery of potent CCR4 antagonists: synthesis and structure–activity relationship study of 2, 4-diaminoquinazolines

K Yokoyama, N Ishikawa, S Igarashi, N Kawano…

Index: Yokoyama, Kazuhiro; Ishikawa, Noriko; Igarashi, Susumu; Kawano, Noriyuki; Hattori, Kazuyuki; Miyazaki, Takahiro; Ogino, Shin-ichi; Matsumoto, Yuzo; Takeuchi, Makoto; Ohta, Mitsuaki Bioorganic and Medicinal Chemistry, 2008 , vol. 16, # 14 p. 7021 - 7032

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Citation Number: 27

Abstract

A new series of quinazolines that function as CCR4 antagonists were discovered during the screening of our corporate compound libraries. Subsequent compound optimization elucidated the structure–activity relationships and led the identification of 2-(1, 4′- bipiperidine-1′-yl)-N-cycloheptyl-6, 7-dimethoxyquinazolin-4-amine 14a, which showed potent inhibition in the [35S] GTPγS-binding assay (IC50= 18nM). This compound also ...