title: Small molecule inhibitors of HIV RT Ribonuclease H.
abstract: Two classes of compounds, thiocarbamates 1 and triazoles 2, have been identified as HIV RT RNase H inhibitors using a novel FRET-based HTS assay. The potent analogs in each series exhibited selectivity and were active in cell-based assays. In addition, saturable, 1:1 stoichiometric binding to target was established and time of addition studies were consistent with inhibition of RT-mediated HIV replication.
authors: Wyeth Research, 401 North Middletown Road, Pearl River, NY, United States. digranm@pfizer.com
authors: Martin
authors: M
authors: Di Grandi
authors: Matthew
authors: M
authors: Olson
authors: Amar S
authors: AS
authors: Prashad
authors: Geraldine
authors: G
authors: Bebernitz
authors: Amara
authors: A
authors: Luckay
authors: Stanley
authors: S
authors: Mullen
authors: Yongbo
authors: Y
authors: Hu
authors: Girija
authors: G
authors: Krishnamurthy
authors: Keith
authors: K
authors: Pitts
authors: John
authors: J
authors: O'Connell
mesh_terms: D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D031541:Fluorescence Resonance Energy Transfer; D057166:High-Throughput Screening Assays; D006801:Humans; D008969:Molecular Sequence Data; D054309:Ribonuclease H, Human Immunodeficiency Virus / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013859:Thiocarbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D013859:Thiocarbamates; D014230:Triazoles; D054309:Ribonuclease H, Human Immunodeficiency Virus