title: Design and synthesis of HIV protease inhibitors. Variations of the carboxy terminus of the HIV protease inhibitor L-682,679.
abstract: A series of tetrapeptide analogues of 1 (L-682,679), in which the carboxy terminus has been shortened and modified, was prepared and their inhibitory activity measured against the HIV protease in a peptide cleavage assay. Selected examples were tested as inhibitors of virus spread in cell culture. Compound 12 was a 10-fold more potent enzyme inhibitor than 1 in vitro and 30-fold more potent in inhibiting the viral spread in cells.
authors.affiliation: Merck Sharp & Dohme Research Laboratories, West Point, Pennsylvania 19486.
authors.forename: S J
authors.initials: SJ
authors.lastname: deSolms
authors.forename: E A
authors.initials: EA
authors.lastname: Giuliani
authors.forename: J P
authors.initials: JP
authors.lastname: Guare
authors.forename: J P
authors.initials: JP
authors.lastname: Vacca
authors.forename: W M
authors.initials: WM
authors.lastname: Sanders
authors.forename: S L
authors.initials: SL
authors.lastname: Graham
authors.forename: J M
authors.initials: JM
authors.lastname: Wiggins
authors.forename: P L
authors.initials: PL
authors.lastname: Darke
authors.forename: I S
authors.initials: IS
authors.lastname: Sigal
authors.forename: J A
authors.initials: JA
authors.lastname: Zugay
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis; D015195:Drug Design; D015683:Gene Products, gag / Q000032:analysis; D015488:HIV Antigens / Q000032:analysis; D016655:HIV Core Protein p24; D017320:HIV Protease Inhibitors; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology / Q000302:isolation & purification / Q000502:physiology; D006801:Humans; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology*; D011498:Protein Precursors / Q000032:analysis; D013601:T-Lymphocytes / Q000382:microbiology; D014758:Viral Core Proteins / Q000032:analysis; D014764:Viral Proteins; D014779:Virus Replication / Q000187:drug effects; D054301:gag Gene Products, Human Immunodeficiency Virus
chemical_list: D000998:Antiviral Agents; D015683:Gene Products, gag; D015488:HIV Antigens; D016655:HIV Core Protein p24; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011498:Protein Precursors; D014758:Viral Core Proteins; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1; C059767:p55 gag precursor protein, Human immunodeficiency virus 1; C070944:L 682679