title: Synthesis and evaluation of 2-pyridinone derivatives as HIV-1-specific reverse transcriptase inhibitors. 4. 3-[2-(Benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one and analogues.
abstract: A new series of potent specific 2-pyridinone reverse transcriptase (RT) inhibitors was developed based on the preliminary development lead 3-[(phthalmido)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (3), a non-nucleoside derivative which exhibited weak antiviral activity in cell culture against HIV-1 strain IIIB. One compound, 3-[(benzoxazol-2-yl)ethyl]-5-ethyl-6-methylpyridin-2(1H)-one (9,L-696,229), which was a highly selective antagonist of the RT enzyme (IC50 = 23 nM) and which inhibited the spread of HIV-1 IIIB infection by > 95% in MT4 human T-lymphoid cell culture (CIC95 = 50-100 nM), was selected for clinical evaluation as an antiviral agent.
authors.affiliation: Department of Medicinal Chemistry, Merck Reserch Laboratories, West Point, Pennsylvania 19486-0004.
authors.forename: J M
authors.initials: JM
authors.lastname: Hoffman
authors.forename: A M
authors.initials: AM
authors.lastname: Smith
authors.forename: C S
authors.initials: CS
authors.lastname: Rooney
authors.forename: T E
authors.initials: TE
authors.lastname: Fisher
authors.forename: J S
authors.initials: JS
authors.lastname: Wai
authors.forename: C M
authors.initials: CM
authors.lastname: Thomas
authors.forename: D L
authors.initials: DL
authors.lastname: Bamberger
authors.forename: J L
authors.initials: JL
authors.lastname: Barnes
authors.forename: T M
authors.initials: TM
authors.lastname: Williams
authors.forename: J H
authors.initials: JH
authors.lastname: Jones
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001583:Benzoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001798:Blood Proteins / Q000378:metabolism; D002478:Cells, Cultured; D004341:Drug Evaluation; D054303:HIV Reverse Transcriptase; D006801:Humans; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018894:Reverse Transcriptase Inhibitors; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D001583:Benzoxazoles; D001798:Blood Proteins; D011728:Pyridones; D018894:Reverse Transcriptase Inhibitors; C076250:L 696229; D054303:HIV Reverse Transcriptase