2. Academic Validation
  3. Discovery of piperidin-4-yl-aminopyrimidines as HIV-1 reverse transcriptase inhibitors. N-benzyl derivatives with broad potency against resistant mutant viruses

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

  • Bioorg Med Chem Lett. 2010 Jul 15;20(14):4215-8. doi: 10.1016/j.bmcl.2010.05.040.
Denis J Kertesz 1,  Christine Brotherton-Pleiss,  Minmin Yang,  Zhanguo Wang,  Xianfeng Lin,  Zongxing Qiu,  Donald R Hirschfeld,  Shelley Gleason,  Taraneh Mirzadegan,  Pete W Dunten,  Seth F Harris,  Armando G Villaseñor,  Julie Qi Hang,  Gabrielle M Heilek,  Klaus Klumpp
Affiliations

Affiliation

  • 1 Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. deniskertesz@comcast.net
PMID: 20538456 DOI: 10.1016/j.bmcl.2010.05.040
Abstract

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.

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