title: Identification of a Potent and Selective GPR4 Antagonist as a Drug Lead for the Treatment of Myocardial Infarction.
abstract: GPR4, a pH-sensing G protein-coupled receptor, is highly expressed in endothelial cells and may be activated in myocardial infarction due the decreased tissue pH. We are interested in GPR4 antagonists as potential effective pharmacologic tools and/or drug leads for the treatment of myocardial infarction. We investigated the structure-activity relationship of a known GPR4 antagonist 1 as a lead compound to identify 3b as the first potent and selective GPR4 antagonist, whose effectiveness was demonstrated in a mouse myocardial infarction model.
authors.affiliation: Faculty of Pharmaceutical Science, Hokkaido University , Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Fukuda
authors.affiliation: Faculty of Pharmaceutical Science, Hokkaido University , Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, Japan.
authors.forename: Saki
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Watari
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University , 3-39-15 Showa-machi, Maebashi 371-8512, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Mogi
authors.affiliation: Faculty of Pharmaceutical Science, Hokkaido University , Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Arisawa
authors.affiliation: Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University , 3-39-15 Showa-machi, Maebashi 371-8512, Japan.
authors.forename: Fumikazu
authors.initials: F
authors.lastname: Okajima
authors.affiliation: Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University , 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurose
authors.affiliation: Faculty of Pharmaceutical Science, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, Japan; Center for Research and Education on Drug Discovery, Hokkaido University, Kita-12, Nishi-6, Kita-Ku, Sapporo 060-0812, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Shuto
keywords: GPR4; dibenzazepine derivatives; myocardial infarction; pH-sensing GPCR