title: Synthesis and evaluation of 2-pyridinone derivatives as specific HIV-1 reverse transcriptase inhibitors. 3. Pyridyl and phenyl analogs of 3-aminopyridin-2(1H)-one.
abstract: In an ongoing effort to develop novel nonnucleoside, specific human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) inhibitors, a series of 3-[(pyridylmethyl)amino]- and 3-[(phenylmethyl)amino]-2-pyridinone derivatives was synthesized and tested for HIV-1 RT inhibitory activity. The more potent compounds have a 2'-methoxy group and 4'- and/or 5'-aliphatic substituents on the pyridyl and phenyl rings. Several of the more potent compounds were also evaluated for antiviral activity in MT-4 cell culture. From this series of compounds, 3-[N-[(5-ethyl-2-methoxy-6-methyl-3-pyridyl)methyl]amino]-5-ethyl-6- methylpyridin-2(1H)-one (6) was selected for clinical evaluation.
authors.affiliation: Merck Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: J S
authors.initials: JS
authors.lastname: Wai
authors.forename: T M
authors.initials: TM
authors.lastname: Williams
authors.forename: D L
authors.initials: DL
authors.lastname: Bamberger
authors.forename: T E
authors.initials: TE
authors.lastname: Fisher
authors.forename: J M
authors.initials: JM
authors.lastname: Hoffman
authors.forename: R J
authors.initials: RJ
authors.lastname: Hudcosky
authors.forename: S C
authors.initials: SC
authors.lastname: MacTough
authors.forename: C S
authors.initials: CS
authors.lastname: Rooney
authors.forename: W S
authors.initials: WS
authors.lastname: Saari
authors.forename: C M
authors.initials: CM
authors.lastname: Thomas
mesh_terms: D000631:Aminopyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002478:Cells, Cultured; D054303:HIV Reverse Transcriptase; D000882:Haplorhini; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D018894:Reverse Transcriptase Inhibitors; D013329:Structure-Activity Relationship
chemical_list: D000631:Aminopyridines; D000998:Antiviral Agents; D011728:Pyridones; D018894:Reverse Transcriptase Inhibitors; C079292:L 702007; D054303:HIV Reverse Transcriptase