2. Academic Validation
  3. Discovery and optimization of pyridazinone non-nucleoside inhibitors of HIV-1 reverse transcriptase

Discovery and optimization of pyridazinone non-nucleoside inhibitors of HIV-1 reverse transcriptase

  • Bioorg Med Chem Lett. 2008 Aug 1;18(15):4352-4. doi: 10.1016/j.bmcl.2008.06.072.
Zachary K Sweeney 1,  James P Dunn,  Yu Li,  Gabrielle Heilek,  Pete Dunten,  Todd R Elworthy,  Xiaochun Han,  Seth F Harris,  Donald R Hirschfeld,  J Heather Hogg,  Walter Huber,  Ann C Kaiser,  Denis J Kertesz,  Woongki Kim,  Taraneh Mirzadegan,  Michael G Roepel,  Y David Saito,  Tania M P C Silva,  Steven Swallow,  Jahari L Tracy,  Armando Villasenor,  Harit Vora,  Amy S Zhou,  Klaus Klumpp
Affiliations

Affiliation

  • 1 Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. [email protected]
PMID: 18632268 DOI: 10.1016/j.bmcl.2008.06.072
Abstract

A series of benzyl pyridazinones were evaluated as HIV-1 non-nucleoside Reverse Transcriptase inhibitors (NNRTIs). Several members of this series showed good activity against the wild-type virus and NNRTI-resistant viruses. The binding of inhibitor 5a to HIV-RT was analyzed by surface plasmon resonance spectroscopy. Pharmacokinetic studies of 5a in rat and dog demonstrated that this compound has good oral bioavailability in animal species. The crystal structure of a complex between HIV-RT and inhibitor 4c is also described.

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