title: Potent cyclic urea HIV protease inhibitors with 3-aminoindazole P2/P2' groups.
abstract: Cyclic ureas containing 3-aminoindazole P2/P2' groups are extremely potent inhibitors of HIV protease. The parent 3-aminoindazole 6 showed a Ki < 0.01 nM but poor translation of enzyme activity to antiviral activity was observed. A series of 3-alkylaminoindazoles revealed that translation improved with increasing lipophilicity. An X-ray crystal structure of 6 bound to HIV protease was obtained.
authors.affiliation: DuPont Merck Pharmaceutical Company, Wilmington, Delaware 19880-0500, USA.
authors.forename: J D
authors.initials: JD
authors.lastname: Rodgers
authors.forename: B L
authors.initials: BL
authors.lastname: Johnson
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: S
authors.initials: S
authors.lastname: Erickson-Viitanen
authors.forename: R M
authors.initials: RM
authors.lastname: Klabe
authors.forename: L
authors.initials: L
authors.lastname: Bacheler
authors.forename: B C
authors.initials: BC
authors.lastname: Cordova
authors.forename: C H
authors.initials: CH
authors.lastname: Chang
mesh_terms: D018360:Crystallography, X-Ray; D015195:Drug Design; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007191:Indazoles / Q000737:chemistry* / Q000494:pharmacology; D007202:Indicators and Reagents; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D017320:HIV Protease Inhibitors; D007191:Indazoles; D007202:Indicators and Reagents; D014508:Urea; D016333:HIV Protease