title: Plasmin inhibitors with hydrophobic amino acid-based linker between hydantoin moiety and benzimidazole scaffold enhance inhibitory activity.
abstract: In this letter we report the design and synthesis of a series of plasmin inhibitors, which share the amino acid-based linker with limited free rotation between the hydantoin moiety and the benzimidazole scaffold. Our studies led to potent plasmin inhibitors and yielded important new insights into their structure-activity relationship for binding to the active site of plasmin.
authors.affiliation: Hiroshima International University, Faculty of Clinical Nutrition, 5-1-1, Hirokoshingai, Kure, Hiroshima 737-0112, Japan. Electronic address: n-teno@ps.hirokoku-u.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Teno
authors.affiliation: Computer-aided Molecular Modeling Research Center, Kansai (CAMM-Kansai), 3-32-302, Tsuto-Otsuka, Nishinomiya 663-8241, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Gohda
authors.affiliation: Hiroshima International University, Faculty of Clinical Nutrition, 5-1-1, Hirokoshingai, Kure, Hiroshima 737-0112, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: Hiroshima International University, Faculty of Pharmaceutical Sciences, 5-1-1, Hirokoshingai, Kure, Hiroshima 737-0112, Japan.
authors.forename: Tadamune
authors.initials: T
authors.lastname: Otsubo
authors.affiliation: Hiroshima International University, Faculty of Pharmaceutical Sciences, 5-1-1, Hirokoshingai, Kure, Hiroshima 737-0112, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Yamaguchi
authors.affiliation: Kobe Research Projects on Thrombosis and Haemostasis, 3-15-18, Asahigaoka, Tarumi-ku, Kobe 655-0033, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Wanaka
authors.affiliation: Kobe Gakuin University, Faculty of Pharmaceutical Sciences, 1-1-3, Minatojima, Chuo-ku, Kobe 650-8586, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsuda
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology*; D005341:Fibrinolysin / Q000037:antagonists & inhibitors*; D006827:Hydantoins / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions
chemical_list: D000596:Amino Acids; D001562:Benzimidazoles; D006827:Hydantoins; D005341:Fibrinolysin
keywords: Benzimidazole; Hydrophobic amino acid; Plasmin inhibitors; Scaffold