Efficient synthesis and gastric (H+/K+)-ATPase-inhibitory activity of 2-aryl-4,5-dihydro-1H-thieno[3,2-e]benzimidazoles.
A series of 2-aryl-4,5-dihydro-1H-thieno[3,2-e]benzimidazoles (1, 2) was prepared by condensation of 5-acylamino-4,5,6,7-tetrahydrobenzo[b]thiophen-4-ones (9, 10) with ammonium acetate under azeotropic reaction conditions. Various congeners, N-methyl and N-phenyl analogues (3-5), 4,5-dihydro-1H-thieno[2,3-e]benzimidazoles (6), 4,5-dihydro-1H-thieno[2,3-g]benzoxazoles (7), and 4,5-dihydro-1H-thieno[2,3-g]benzothiazoles (8), were also prepared. Several compounds in this series were shown to be K(+)-competitive inhibitors of the gastric (H+/K+)-ATPase and more potent inhibitors than SK&F-96067, 3-butyryl-8-methoxy-4-(2-tolylamino)quinoline, on pentagastrin-stimulated acid secretion in chronic gastric fistula rats after intraduodenal administration.
Homma
K
K
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Watanabe
T
T
Iijima
T
T
Yato
M
M
Matsuki
K
K
Noto
T
T
Ishida
A
A
D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004195:Disease Models, Animal; D004386:Duodenum; D004791:Enzyme Inhibitors / Q000138:chemical synthesis*; D005744:Gastric Acid / Q000378:metabolism; D005747:Gastric Fistula / Q000188:drug therapy; D005748:Gastric Fundus / Q000187:drug effects / Q000201:enzymology*; D010418:Pentagastrin / Q000037:antagonists & inhibitors; D054328:Proton Pump Inhibitors; D051381:Rats; D013329:Structure-Activity Relationship
D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D010418:Pentagastrin