title: Discovery of triazolinone non-nucleoside inhibitors of HIV reverse transcriptase.
abstract: Novel non-nucleoside inhibitors of HIV-RT that contain pyridazinone isosteres were prepared, and a series of triazolinones were found to be potent inhibitors of HIV replication. These compounds were active against several NNRTI-resistant virus strains. Pharmacokinetic studies indicated that inhibitor 7e has good bioavailability in rats. Several fragments of inhibitor 7c were prepared, and the binding of these compounds to HIV-RT was analyzed by surface plasmon resonance spectroscopy.
authors.affiliation: Roche Palo Alto LLC, 3431 Hillview Avenue, Palo Alto, CA 94304, USA. zachary.sweeney@roche.com
authors.forename: Zachary K
authors.initials: ZK
authors.lastname: Sweeney
authors.forename: Sahaja
authors.initials: S
authors.lastname: Acharya
authors.forename: Andrew
authors.initials: A
authors.lastname: Briggs
authors.forename: James P
authors.initials: JP
authors.lastname: Dunn
authors.forename: Todd R
authors.initials: TR
authors.lastname: Elworthy
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fretland
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Giannetti
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Heilek
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Ann C
authors.initials: AC
authors.lastname: Kaiser
authors.forename: Michael
authors.initials: M
authors.lastname: Martin
authors.forename: Y David
authors.initials: YD
authors.lastname: Saito
authors.forename: Mark
authors.initials: M
authors.lastname: Smith
authors.forename: Judy M
authors.initials: JM
authors.lastname: Suh
authors.forename: Steven
authors.initials: S
authors.lastname: Swallow
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Wu
authors.forename: Julie Q
authors.initials: JQ
authors.lastname: Hang
authors.forename: Amy S
authors.initials: AS
authors.lastname: Zhou
authors.forename: Klaus
authors.initials: K
authors.lastname: Klumpp
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques; D024882:Drug Resistance, Viral / Q000187:drug effects; D015394:Molecular Structure; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D011724:Pyridazines; D018894:Reverse Transcriptase Inhibitors; D014230:Triazoles