title: Pyrrolopyrimidine-inhibitors with hydantoin moiety as spacer can explore P4/S4 interaction on plasmin.
abstract: In the development of plasmin inhibitors, a novel chemotype, pyrrolopyrimidine scaffold possessing two motifs, a hydantoin-containing P4 moiety and a warhead-containing P1 moiety, is uncovered. A unique feature of the new line of the plasmin inhibitors is that the interaction between the plasmin inhibitors and key subsites in plasmin can be controlled by a spacer like hydantoin. The application of the novel chemotype is demonstrated by 1n and provides further evidence on the importance of hydantoin as the spacer.
authors.affiliation: Hiroshima International University, Faculty of Pharmaceutical Sciences, 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), 5-1-7, Ohmichidori, Nagata-ku, Kobe 653-0833, Japan.
authors.forename: Keigo
authors.initials: K
authors.lastname: Gohda
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
authors.affiliation: Hiroshima International University, Faculty of Pharmaceutical Sciences, 5-1-1, Hirokoshingai, Kure, Hiroshima 737-0112, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Sueda
authors.affiliation: Hiroshima International University, Faculty of Pharmaceutical Sciences, 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
mesh_terms: D000933:Antifibrinolytic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005341:Fibrinolysin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000933:Antifibrinolytic Agents; D011743:Pyrimidines; D011758:Pyrroles; C527741:pyrrolopyrimidine; D005341:Fibrinolysin
keywords: Hydantoin; P4 moiety; Plasmin inhibitors; Pyrrolopyrimidine; Scaffold; Structure–activity relationship