title: Novel inhibitors of HIV protease: design, synthesis and biological evaluation of picomolar inhibitors containing cyclic P1/P2 scaffolds.
abstract: A novel series of HIV protease inhibitors containing cyclic P1/P2 scaffolds has been synthesized and evaluated for biological activity. The trans 3,5-dibenzyl-2-oxo pyrrolidinone ring system resulted in a 50 pM enzyme inhibitor against HIV protease in vitro when combined with an indanolamine derived P'-backbone. This compound also shows comparable activity to currently marketed drugs in the MT-4 cell-based antiviral assay.
authors.affiliation: Glaxo Wellcome Inc, NC 27709, USA. as11513@glaxowellcome.com
authors.forename: A
authors.initials: A
authors.lastname: Spaltenstein
authors.forename: M R
authors.initials: MR
authors.lastname: Almond
authors.forename: W J
authors.initials: WJ
authors.lastname: Bock
authors.forename: D G
authors.initials: DG
authors.lastname: Cleary
authors.forename: E S
authors.initials: ES
authors.lastname: Furfine
authors.forename: R J
authors.initials: RJ
authors.lastname: Hazen
authors.forename: W M
authors.initials: WM
authors.lastname: Kazmierski
authors.forename: F G
authors.initials: FG
authors.lastname: Salituro
authors.forename: R D
authors.initials: RD
authors.lastname: Tung
authors.forename: L L
authors.initials: LL
authors.lastname: Wright
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D013844:Thiazoles