title: Synthesis and antiviral property of allophenylnorstatine-based HIV protease inhibitors incorporating D-cysteine derivatives as P2/P3 moieties.
abstract: We designed several HIV protease inhibitors with various d-cysteine derivatives as P(2)/P(3) moieties based on the structure of clinical drug candidate, KNI-764. Herein, we report their synthesis, HIV protease inhibitory activity, HIV IIIB cell inhibitory activity, cellular toxicity, and inhibitory activity against drug-resistant HIV strains. KNI-1931 showed distinct selectivity against HIV proteases and high potency against drug-resistant strains, surpassing those of Ritonavir and Nelfinavir.
authors.affiliation: Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science and 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
authors.forename: Ei'ichi
authors.initials: E
authors.lastname: Ami
authors.forename: Koichiro
authors.initials: K
authors.lastname: Nakahara
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sato
authors.forename: Jeffrey-Tri
authors.initials: JT
authors.lastname: Nguyen
authors.forename: Koushi
authors.initials: K
authors.lastname: Hidaka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hamada
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakatani
authors.forename: Tooru
authors.initials: T
authors.lastname: Kimura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D003545:Cysteine / Q000737:chemistry*; D006678:HIV / Q000187:drug effects; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D010654:Phenylbutyrates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000577:Amides; D017320:HIV Protease Inhibitors; C430091:KNI 764; D010654:Phenylbutyrates; D013844:Thiazoles; C034940:3-amino-2-hydroxy-4-phenylbutanoic acid; D003545:Cysteine