title: Structure-activity relationships of HIV-1 PR inhibitors containing AHPBA.
abstract: A series of Human Immunodeficiency Virus type-1 protease (HIV-1 PR) inhibitors that contain 3-amino-2-hydroxy-4-phenylbutanoic acid (AHPBA) at the scission site of the substrate were prepared and evaluated for their inhibitory activity. Preliminary studies on the chain length of inhibitors and the hydroxyl configuration of AHPBA indicated that small (2S,3S)-derivatives, composed of the regions between the P3 and P2' sites, showed enough inhibitory activity toward HIV-1 PR to become prototypes for further structural modification. Systematic replacement at the sites from P3 to P2' revealed that some bicyclic heteroarylcarbonyl derivatives possessed strong potency and good enzyme selectivity.
authors.affiliation: Exploratory Chemistry Research, Sankyo Co. Ltd, Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Sakurai
authors.forename: S
authors.initials: S
authors.lastname: Higashida
authors.forename: M
authors.initials: M
authors.lastname: Sugano
authors.forename: T
authors.initials: T
authors.lastname: Komai
authors.forename: R
authors.initials: R
authors.lastname: Yagi
authors.forename: Y
authors.initials: Y
authors.lastname: Ozawa
authors.forename: H
authors.initials: H
authors.lastname: Handa
authors.forename: T
authors.initials: T
authors.lastname: Nishigaki
authors.forename: Y
authors.initials: Y
authors.lastname: Yabe
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000614:Aminocaproates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000596:Amino Acids; D000614:Aminocaproates; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; C034495:3-amino-2-hydroxy-5-methylhexanoic acid