Discovery of piperidin-4-yl-aminopyrimidines as HIV-1 reverse transcriptase inhibitors. N-Benzyl derivatives with broad potency against resistant mutant viruses

An analysis of the binding motifs of known HIV-1 non-nucleoside reverse transcriptase inhibitors has led to discovery of novel piperidine-linked aminopyrimidine derivatives with broad activity against wild-type as well as drug-resistant mutant viruses. Notably, the series retains potency against the...

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Veröffentlicht in:Bioorganic & medicinal chemistry letters 2010-07, Vol.20 (14), p.4215-4218
Hauptverfasser: Kertesz, Denis J., Brotherton-Pleiss, Christine, Yang, Minmin, Wang, Zhanguo, Lin, Xianfeng, Qiu, Zongxing, Hirschfeld, Donald R., Gleason, Shelley, Mirzadegan, Taraneh, Dunten, Pete W., Harris, Seth F., Villaseñor, Armando G., Hang, Julie Qi, Heilek, Gabrielle M., Klumpp, Klaus
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Sprache:eng
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Zusammenfassung:An analysis of the binding motifs of known HIV-1 non-nucleoside reverse transcriptase inhibitors has led to discovery of novel piperidine-linked aminopyrimidine derivatives with broad activity against wild-type as well as drug-resistant mutant viruses. Notably, the series retains potency against the K103N/Y181C and Y188L mutants, among others. Thus, the N-benzyl compound 5k has a particularly attractive profile. Synthesis and SAR are presented and discussed, as well as crystal structures relating to the binding motifs.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2010.05.040