Optimization of 2,4-diarylanilines as non-nucleoside HIV-1 reverse transcriptase inhibitors

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

卷:22

Article

Sun, Lian-Qi¹  Qin, Bingjie¹  Huang, Li²  Qian, Keduo³  Chen, Chin-Ho²  Lee, Kuo-Hsiung^3,4  Xie, Lan¹ 

[1] Beijing Inst Pharmacol & Toxicol, Beijing 100850, Peoples R China

[2] Duke Univ, Med Ctr, Surg Oncol Res Facil, Durham, NC 27710 USA

[3] Univ N Carolina, Nat Prod Res Labs, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA

[4] China Med Univ & Hosp, Chinese Med Res & Dev Ctr, Taichung, Taiwan

关键词: Diarylaniline;    NNRTIs;    Lead optimization;    Anti-HIV agents;   

DOI  :  10.1016/j.bmcl.2012.02.055

来源: Elsevier

【 摘 要 】

The current optimization of 2,4-diarylaniline analogs (DAANs) on the central phenyl ring provided a series of new active DAAN derivatives 9a-9e, indicating an accessible modification approach that could improve anti-HIV potency against wild-type and resistant strains, aqueous solubility, and metabolic stability. A new compound 9e not only exhibited extremely high potency against wild-type virus (EC50 0.53 nM) and several resistant viral strains (EC50 0.36-3.9 nM), but also showed desirable aqueous solubility and metabolic stability, which were comparable or better than those of the anti-HIV-1 drug TMC278 (2). Thus, new compound 9e might be a potential drug candidate for further development of novel next-generation NNRTIs. (C) 2012 Elsevier Ltd. All rights reserved.

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