Evaluation of retro-inverso modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster.
Effects of retro-inverso (RI) modifications of HTLV-1 protease inhibitors containing a hydroxyethylamine isoster backbone were clarified. Construction of the isoster backbone was achieved by a stereoselective aldol reaction. Four diastereomers with different configurations at the isoster hydroxyl site and the scissile site substituent were synthesized. Inhibitory activities of the new inhibitors suggest that partially modified RI inhibitors would interact with HTLV-1 protease in the same manner as the parent hydroxyethylamine inhibitor.
Department of Medicinal Chemistry, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kita-ku, Kyoto 603-8334, Japan.
Tadashi
T
Tatsumi
Chiyuki
C
Awahara
Hiromi
H
Naka
Saburo
S
Aimoto
Hiroyuki
H
Konno
Kazuto
K
Nosaka
Kenichi
K
Akaji
D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000235:genetics; D003642:Deanol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015368:Human T-lymphotropic virus 1 / Q000187:drug effects / Q000235:genetics; D007202:Indicators and Reagents; D009154:Mutation; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D007202:Indicators and Reagents; D011480:Protease Inhibitors; D003642:Deanol; D016282:Aspartic Acid Endopeptidases; C079711:HTLV-1 protease