title: Novel spirocyclic pyrrolidones as P2/P1 mimetics in potent inhibitors of HIV-1 protease.
abstract: We have developed concise and efficient syntheses of novel spirocyclic pyrrolidones 1-3, which involve the alkylation of pyrrolidone precursor 13 with 1,5-dibromopentane, 16 and 15, followed by an in situ lactamization. Conjugates of 1 and 2 with P1'/P2' hydroxy-indanolamine moiety resulted in novel and potent inhibitors of HIV-1 protease 25 and 26, suggesting that 1 and 2 are novel P2/P1 HIV-PI mimetics.
authors.affiliation: GlaxoSmithKline, Research Triangle Park, NC 27709, USA. wieslaw.m.kazmierski@gsk.com
authors.forename: Wieslaw M
authors.initials: WM
authors.lastname: Kazmierski
authors.forename: Eric
authors.initials: E
authors.lastname: Furfine
authors.forename: Andrew
authors.initials: A
authors.lastname: Spaltenstein
authors.forename: Lois L
authors.initials: LL
authors.lastname: Wright
mesh_terms: D000478:Alkylation; D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology; D040761:Biomimetic Materials / Q000737:chemistry / Q000494:pharmacology; D017320:HIV Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D007769:Lactams / Q000737:chemistry; D011760:Pyrrolidinones / Q000737:chemistry* / Q000494:pharmacology*; D013141:Spiro Compounds / Q000737:chemistry / Q000494:pharmacology
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D007769:Lactams; D011760:Pyrrolidinones; D013141:Spiro Compounds