title: Optimization of 2,4-diarylanilines as non-nucleoside HIV-1 reverse transcriptase inhibitors.
abstract: 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 (EC(50) 0.53 nM) and several resistant viral strains (EC(50) 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.
authors.affiliation: Beijing Institute of Pharmacology & Toxicology, 27 Tai-Ping Road, Beijing 100850, China.
authors.forename: Lian-Qi
authors.initials: LQ
authors.lastname: Sun
authors.forename: Bingjie
authors.initials: B
authors.lastname: Qin
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.forename: Keduo
authors.initials: K
authors.lastname: Qian
authors.forename: Chin-Ho
authors.initials: CH
authors.lastname: Chen
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
authors.forename: Lan
authors.initials: L
authors.lastname: Xie
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D024882:Drug Resistance, Viral; D004355:Drug Stability; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D020128:Inhibitory Concentration 50; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D009570:Nitriles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D000068696:Rilpivirine; D012995:Solubility
chemical_list: D000814:Aniline Compounds; D019380:Anti-HIV Agents; D009570:Nitriles; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D000068696:Rilpivirine