Synthesis of (aryloxy)alkylamines. 1. Novel antisecretory agents with H+K+-ATPase inhibitory activity.

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Sanfilippo PJ, Urbanski M, Press JB, Hajos ZG, Shriver DA, Scott CK

Synthesis of (aryloxy)alkylamines. 1. Novel antisecretory agents with H+K+-ATPase inhibitory activity.

J Med Chem. 1988 Sep;31(9):1778-85.

PubMed ID

2842503 [ View in PubMed

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Abstract

A series of heterocyclic (aryloxy)alkylamines of structures II and III were prepared and found to possess gastric antisecretory activity. Of the variety of substituted thiazoles, benzoxazoles, and benzothiazoles prepared, thiazole 18, benzoxazole 32, and benzothiazole 47 exhibited gastric antisecretory potency comparable to that of ranitidine in vivo in the pylorous ligated rat model. In an isolated rabbit parietal system, the series of thiazoles, benzoxazoles, and benzothiazoles also demonstrated similar potency to that of ranitidine toward the inhibition of both histamine-stimulated and dcAMP-stimulated uptake of amino[14C]pyrine. These compounds inhibited the H+K+-sensitive ATPase enzyme in isolated gastric microsomes. A direct correlation existed between inhibition of 14C uptake, in vivo antisecretory activity, and inhibition of the H+K+-ATPase enzyme. The more potent antisecretory compounds 18, 32, and 47 were also the more potent enzyme inhibitors. These data suggest that the mechanism responsible for the observed in vitro and in vivo gastric antisecretory activity, in these series of compounds, is a consequence of the inhibition of the H+K+-sensitive ATPase enzyme.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Omeprazole	Potassium-transporting ATPase alpha chain 1	IC 50 (nM)	250	N/A	N/A	Details
Omeprazole	Potassium-transporting ATPase alpha chain 1	IC 50 (nM)	280	N/A	N/A	Details