title: Aminodiol HIV protease inhibitors. Synthesis and structure-activity relationships of P1/P1' compounds: correlation between lipophilicity and cytotoxicity.
abstract: A series of novel aminodiol inhibitors of HIV protease based on the lead compound 1 with structural modifications at P1' were synthesized in order to reduce the cytotoxicity of 1. We have observed a high degree of correlation between the lipophilicity and cytotoxicity of this series of inhibitors. It was found that appropriate substitution at the para position of the P1' phenyl group of 1 resulted in the identification of equipotent (both against the enzyme and in cell culture) compounds (10l, 10m, 10n, and 15c) which possess significantly decreased cytotoxicity.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000, USA.
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.forename: P T
authors.initials: PT
authors.lastname: Cheng
authors.forename: M
authors.initials: M
authors.lastname: Alam
authors.forename: B D
authors.initials: BD
authors.lastname: Beyer
authors.forename: G S
authors.initials: GS
authors.lastname: Bisacchi
authors.forename: T
authors.initials: T
authors.lastname: Dejneka
authors.forename: A J
authors.initials: AJ
authors.lastname: Evans
authors.forename: J A
authors.initials: JA
authors.lastname: Greytok
authors.forename: M A
authors.initials: MA
authors.lastname: Hermsmeier
authors.forename: W G
authors.initials: WG
authors.lastname: Humphreys
authors.forename: G A
authors.initials: GA
authors.lastname: Jacobs
authors.forename: O
authors.initials: O
authors.lastname: Kocy
authors.forename: P F
authors.initials: PF
authors.lastname: Lin
authors.forename: K A
authors.initials: KA
authors.lastname: Lis
authors.forename: M A
authors.initials: MA
authors.lastname: Marella
authors.forename: D E
authors.initials: DE
authors.lastname: Ryono
authors.forename: A K
authors.initials: AK
authors.lastname: Sheaffer
authors.forename: S H
authors.initials: SH
authors.lastname: Spergel
authors.forename: C Q
authors.initials: CQ
authors.lastname: Sun
authors.forename: J A
authors.initials: JA
authors.lastname: Tino
authors.forename: G
authors.initials: G
authors.lastname: Vite
authors.forename: R J
authors.initials: RJ
authors.lastname: Colonno
authors.forename: R
authors.initials: R
authors.lastname: Zahler
authors.forename: J C
authors.initials: JC
authors.lastname: Barrish
mesh_terms: D000588:Amines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D017320:HIV Protease Inhibitors