基于螺环二酮哌嗪的 CCR5 拮抗剂：抗逆转录病毒候选药物的发现。
Spirodiketopiperazine-based CCR5 antagonist: discovery of an antiretroviral drug candidate.
机构信息
Medicinal Chemistry Research Laboratory, Ono Pharmaceutical Co., Ltd, Shimamoto, Mishima, Osaka 618-8585, Japan.
出版信息
Bioorg Med Chem Lett. 2011 Feb 15;21(4):1141-5. doi: 10.1016/j.bmcl.2010.12.109. Epub 2010 Dec 28.
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 pharmaceutical profile for use as a drug candidate.
摘要
继发现羟基衍生物 3（图 1）是原始先导化合物 1 的氧化代谢物之一后，人们发现羟基化合物 4 比相应的非羟基化合物 2 具有更高的体外抗 HIV 活性。将 4 与可口服的类似物 5 进行结构杂化，得到另一种可口服的螺二酮哌嗪 CCR5 拮抗剂 6a，其具有更有利的药物特性，可作为候选药物。
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