title: Design, synthesis, and structure-activity relationships of 3,4-dihydropyridopyrimidin-2(1H)-one derivatives as a novel class of sodium/calcium exchanger inhibitor.
abstract: Design, synthesis, and structure-activity relationships for 3,4-dihydropyridopyrimidin-2(1H)-one derivatives, which are aza-3,4-dihydro-2(1H)-quinazolinone derivatives, as the sodium/calcium (Na+/Ca2+) exchanger inhibitors are discussed. These studies based on 3,4-dihydro-2(1H)-quinazolinone derivatives led to the discovery of a structurally novel and potent Na+/Ca2+ exchanger inhibitor, 3,4-dihydropyridopyrimidin-2(1H)-one derivative (26), with an IC30 value of 0.02 microM. Compound 26 directly inhibited the Na+-dependent Ca2+ influx via the Na+/Ca2+ exchanger after Na+-free treatment in cardiomyocytes.
authors.affiliation: Research Division, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan. hhasegaw@sumitopharm.co.jp
authors.forename: Hirohiko
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Masami
authors.initials: M
authors.lastname: Muraoka
authors.forename: Mikiko
authors.initials: M
authors.lastname: Ohmori
authors.forename: Kazuki
authors.initials: K
authors.lastname: Matsui
authors.forename: Atsuyuki
authors.initials: A
authors.lastname: Kojima
mesh_terms: D000818:Animals; D015394:Molecular Structure; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: C507290:3,4-dihydropyridopyrimidin-2(1H)-one; D011744:Pyrimidinones; D019831:Sodium-Calcium Exchanger