Discovery, synthesis, and structure-activity relations of 3,4-dihydro-1H-spiro(naphthalene-2,2′-piperidin)-1-ones as potassium-competitive acid blockers

Add time:09/01/2019    Source:sciencedirect.com

With the aim to discover a gastric antisecretory agent more potent than the existing proton pump inhibitors, novel 3,4-dihydro-1H-spiro(naphthalene-2,2′-piperidin)-1-one derivatives, which could occupy two important lipophilic pockets (described as LP-1 and LP-2) of H+,K+-ATPase and can strongly bind to the K+-binding site, were designed based on a docking model. Among the compounds synthesized, compound 4d showed a strong H+,K+-ATPase-inhibitory activity and a high stomach concentration in rats, resulting in potent inhibitory action on histamine-stimulated gastric acid secretion in rats. Furthermore, 4d exerted significant inhibitory action on histamine-stimulated gastric-acid secretion in rats with a rapid onset and moderate duration of action after the administration. These findings may lead to a new insight into the drug design of potassium-competitive acid blockers.

We also recommend Trading Suppliers and Manufacturers of PIPERIDIN-2-YL-ACETIC ACID HYDROCHLORIDE (cas 19615-30-6). Pls Click Website Link as below: cas 19615-30-6 suppliers

Prev:Original ArticleIdentification, synthesis and characterization of process related impurities of benidipine hydrochloride, stress-testing/stability studies and HPLC/UPLC method validations☆
Next:Allosteric modulation of sigma receptors by BH3 mimetics ABT-737, ABT-263 (Navitoclax) and ABT-199 (Venetoclax))