Discovery of 4-[4-({(3R)-1-butyl-3-[(R)-cyclohexyl (hydroxy) methyl]-2, 5-dioxo-1, 4, 9-triazaspiro [5.5] undec-9-yl} methyl) phenoxy] benzoic acid hydrochloride: a …

…, T Nishiyama, K Hisaichi, C Minamoto, M Murota…

Index: Nishizawa, Rena; Nishiyama, Toshihiko; Hisaichi, Katsuya; Minamoto, Chiaki; Murota, Masayuki; Takaoka, Yoshikazu; Nakai, Hisao; Tada, Hideaki; Sagawa, Kenji; Shibayama, Shiro; Fukushima, Daikichi; Maeda, Kenji; Mitsuya, Hiroaki Bioorganic and Medicinal Chemistry, 2011 , vol. 19, # 13 p. 4028 - 4042

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Citation Number: 7

Abstract

Abstract Based on the original spirodiketopiperazine design framework, further optimization of an orally available CCR5 antagonist was undertaken. Structural hybridization of the hydroxylated analog 4 derived from one of the oxidative metabolites and the new orally available non-hydroxylated benzoic acid analog 5 resulted in another potent orally available CCR5 antagonist 6a as a clinical candidate. Full details of a structure–activity relationship ...