title: Two-carbon-elongated HIV-1 protease inhibitors with a tertiary-alcohol-containing transition-state mimic.
abstract: A new generation of HIV-1 protease inhibitors encompassing a tertiary-alcohol-based transition-state mimic has been developed. By elongation of the core structure of recently reported inhibitors with two carbon atoms and by varying the P1' group of the compounds, efficient inhibitors were obtained with Ki down to 2.3 nM and EC50 down to 0.17 microM. Two inhibitor-enzyme X-ray structures are reported.
authors.affiliation: Department of Medicinal Chemistry, Organic Pharmaceutical Chemistry, BMC, Uppsala University, Box 574, SE-751 23 Uppsala, Sweden.
authors.forename: Xiongyu
authors.initials: X
authors.lastname: Wu
authors.forename: Per
authors.initials: P
authors.lastname: Ohrngren
authors.forename: Jenny K
authors.initials: JK
authors.lastname: Ekegren
authors.forename: Johan
authors.initials: J
authors.lastname: Unge
authors.forename: Torsten
authors.initials: T
authors.lastname: Unge
authors.forename: Hans
authors.initials: H
authors.lastname: Wallberg
authors.forename: Bertil
authors.initials: B
authors.lastname: Samuelsson
authors.forename: Anders
authors.initials: A
authors.lastname: Hallberg
authors.forename: Mats
authors.initials: M
authors.lastname: Larhed
mesh_terms: D000438:Alcohols / Q000737:chemistry*; D001665:Binding Sites; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D018360:Crystallography, X-Ray; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D006834:Hydrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D018716:Molecular Mimicry; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism
chemical_list: C528860:(1-(N'-(4-hydroxy-4-(2-hydroxyindan-1-ylcarbamoyl)-5-phenylpentyl)-N'-(4-pyridin-4-ylbenzyl)hydrazinocarbonyl)-2,2-dimethylpropyl)carbamic acid methyl ester; D000438:Alcohols; D002219:Carbamates; D017320:HIV Protease Inhibitors; D006834:Hydrazines; D007093:Imidazoles; D010069:Oxadiazoles; D011725:Pyridines