发现可口服的基于螺环二酮哌嗪的 CCR5 拮抗剂。
Discovery of orally available spirodiketopiperazine-based CCR5 antagonists.
机构信息
Minase Research Institute, Ono Pharmaceutical Co., Ltd, Shimamoto, Mishima, Osaka 618-8585, Japan.
出版信息
Bioorg Med Chem. 2010 Jul 15;18(14):5208-23. doi: 10.1016/j.bmc.2010.05.057. Epub 2010 May 25.
Abstract
Using the previously reported novel spirodiketopiperazine scaffold, the design and synthesis of orally available CCR5 antagonists was undertaken. Compounds possessing a carboxylic acid function in the appropriate position showed improved oral exposure (AUC) relative to the initial chemical leads without reduction in the antagonist activity. The optimized compound 40 was found to show potent anti-HIV activity. Full details of structure-activity relationship (SAR) study are presented.
摘要
利用先前报道的新型螺环二酮哌嗪骨架，我们设计并合成了可口服的 CCR5 拮抗剂。在不降低拮抗活性的情况下，在适当位置具有羧酸官能团的化合物显示出改善的口服暴露（AUC）。优化后的化合物 40 被发现具有很强的抗 HIV 活性。本文详细介绍了构效关系（SAR）研究的全部内容。
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