二芳基嘧啶类HIV-1非核苷类逆转录酶抑制剂研究进展
Discovery and development of diarylpyrimidines (DAPYs) as next-generation HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs)
田兴涛 1谢蓝1
作者信息
- 1. 军事医学科学院毒物药物研究所,北京,100850
- 折叠
摘要
2008年FDA批准上市的新一代非核苷类逆转录酶抑制剂Etravirine(TMCl25)和Ⅲ期临床候选药Rilpivirine(TMC278)都是二芳基嘧啶(DAPY)类化合物,均对HIV野生型和多种耐药性病毒株有相当强的抑制作用.DAPY类药物的发现和发展是多学科合作研发新药的成功范例.本文综述了新一代HIV 非核苷类逆转录酶抑制剂DAPY类化合物的发现、发展及最新研究进展.
Abstract
The new HIV-1 NNRTI drug Etravirine (TMC125) and a promising drug candidate Rilpivirine (TMC278) in phase Ⅲ clinical trial are compounds belonging to the diarylpyrimidine (DAPY) family. They are extremely high potent against both wild-type and many drug-resistant HIV-1 strains, providing new hope for HIV-infected patients who fail to use current drugs due to the emergence of drug-resistant HIV mutants. The discovery and development of DAPY derivatives as next-generation NNRTI drugs depend on multidisciplinary coordination and their success has encouraged new researches to explore more next-generation NNRTIs with new scaffolds. This review described the story of discovery and development of DAPY derivatives as next-generation NNRTIs and related progress.
关键词
人类免疫缺陷病毒/非核苷类逆转录酶抑制剂/二芳基嘧啶类化合物/Etravirine/RilpivirineKey words
HIV-1/NNRTI/diarylpyrimidine/Etravirine/Rilpivirine引用本文复制引用
基金项目
国家自然科学基金(20472114)
北京市自然科学基金(7052057)
出版年
2010
NETL
NSTL
维普
万方数据