title: Discovery, synthesis, and biological evaluation of novel pyrrole derivatives as highly selective potassium-competitive acid blockers.
abstract: To discover a gastric antisecretory agent more potent than existing proton pump inhibitors, novel pyrrole derivatives were synthesized, and their H(+),K(+)-ATPase inhibitory activities and inhibitory action on histamine-stimulated gastric acid secretion in rats were evaluated. Among the compounds synthesized, compound 17a exhibited selective and potent H(+),K(+)-ATPase inhibitory activity through reversible and K(+)-competitive ionic binding; furthermore, compound 17c exhibited potent inhibitory action on histamine-stimulated gastric acid secretion in rats and Heidenhain pouch dogs.
authors.affiliation: Pharmaceutical Research Division, Takeda Pharmaceutical Company, Ltd., 26-1, Muraokahigashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. haruyuki.nishida@takeda.com
authors.forename: Haruyuki
authors.initials: H
authors.lastname: Nishida
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hasuoka
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Arikawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Kurasawa
authors.forename: Keizo
authors.initials: K
authors.lastname: Hirase
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Inatomi
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hori
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Sato
authors.forename: Naoki
authors.initials: N
authors.lastname: Tarui
authors.forename: Akio
authors.initials: A
authors.lastname: Imanishi
authors.forename: Mitsuyo
authors.initials: M
authors.lastname: Kondo
authors.forename: Terufumi
authors.initials: T
authors.lastname: Takagi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kajino
mesh_terms: D000818:Animals; D004285:Dogs; D055808:Drug Discovery; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D008297:Male; D008958:Models, Molecular; D015394:Molecular Structure; D054328:Proton Pump Inhibitors; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000201:enzymology; D013329:Structure-Activity Relationship; D013552:Swine
chemical_list: D054328:Proton Pump Inhibitors; D011758:Pyrroles; D017506:H(+)-K(+)-Exchanging ATPase