A substituted thieno[3.4-d]imidazole versus substituted benzimidazoles as H+, K+-ATPase inhibitors.
S 3337, 2-(2-ethylaminobenzylsulfinyl)-5,6-dimethoxybenzimidazole, and S 1924, 2-(5-methyl-2-picolylsulfinyl)-1H-thieno[3.4-d]imidazole, are members of new classes of H+, K+-ATPase inhibitors. Their effects on H+, K+-ATPase and 14C-aminopyrine uptake in gastric glands were studied as well as in vivo in pylorus-ligated rats, stomach-lumen-perfused rats and Heidenhain pouch dogs. Their inhibitory effects were compared with the effect of omeprazole. In pylorus-ligated rats the two compounds showed a similar effectiveness as omeprazole. In stomach-lumen-perfused rats and in particular in Heidenhain pouch dogs, S 3337 was clearly less effective than omeprazole, while S 1924 was similarly effective in all in vivo models and in the H+, K+-ATPase assay as omeprazole. The difference in potency between S 1924 and omeprazole on 14C-aminopyrine uptake in gastric glands can be explained by the lower pKa value of S 1924 (3.4) than that of omeprazole (4.0). Additionally, this study shows that there was no correlation between the effects in rats, particularly in pylorus-ligated rats, and in dogs for the H+, K+-ATPase inhibitors tested. It is concluded from this study that substituted thieno[3.4-d]imidazoles represent a new class of potent gastric acid inhibitors.
Herling
A W
AW
Hoechst AG, Frankfurt/Main, FRG.
Bickel
M
M
Lang
H J
HJ
Weidmann
K
K
Rösner
M
M
Metzger
H
H
Rippel
R
R
Nimmesgern
H
H
Scheunemann
K H
KH
D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D000632:Aminopyrine / Q000378:metabolism; D000818:Animals; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D004285:Dogs; D017506:H(+)-K(+)-Exchanging ATPase; D007093:Imidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009853:Omeprazole / Q000494:pharmacology / Q000031:analogs & derivatives; D011708:Pylorus / Q000502:physiology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000201:enzymology; D013552:Swine
D001562:Benzimidazoles; D007093:Imidazoles; D000632:Aminopyrine; C056861:2-(2-ethylaminobenzylsulfinyl)-5,6-dimethoxybenzimidazole; C056862:S 1924; D000251:Adenosine Triphosphatases; D017506:H(+)-K(+)-Exchanging ATPase; D009853:Omeprazole