Spirodiketopiperazine-based CCR5 antagonist: Discovery of an antiretroviral drug candidate

…, H Nakai, S Jenkinson, WM Kazmierski, H Tada…

Index: Nishizawa, Rena; Nishiyama, Toshihiko; Hisaichi, Katsuya; Minamoto, Chiaki; Matsunaga, Naoki; Takaoka, Yoshikazu; Nakai, Hisao; Jenkinson, Stephen; Kazmierski, Wieslaw M.; Tada, Hideaki; Sagawa, Kenji; Shibayama, Shiro; Fukushima, Daikichi; Maeda, Kenji; Mitsuya, Hiroaki Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 4 p. 1141 - 1145

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Citation Number: 9

Abstract

Following the discovery that hydroxylated derivative 3 (Fig. 1) was one of the oxidative metabolites of the original lead 1, it was found that hydroxylated compound 4 possesses higher in vitro anti-HIV potency than the corresponding non-hydroxylated compound 2. Structural hybridation of 4 with the orally available analog 5 resulted in another orally- available spirodiketopiperazine CCR5 antagonist 6a that possesses more favorable ...