- Discovery, synthesis, and structure-activity relations of 3,4-dihydro-1H-spiro(naphthalene-2,2′-piperidin)-1-ones as potassium-competitive acid blockers
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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.
- Imaeda, Toshihiro,Ono, Koji,Nakai, Kazuo,Hori, Yasunobu,Matsukawa, Jun,Takagi, Terufumi,Fujioka, Yasushi,Tarui, Naoki,Kondo, Mitsuyo,Imanishi, Akio,Inatomi, Nobuhiro,Kajino, Masahiro,Itoh, Fumio,Nishida, Haruyuki
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p. 3719 - 3735
(2017/06/13)
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- Condensed heterocyclic compounds, their production and use
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The compound STR1 wherein ring A represents a benzene ring; Ar represents an aromatic group; R 1 and R 2 independently represent hydrogen, acyl or hydrocarbon group or R 1 and R 2 taken together with the adjacent nitrogen atom represent a nitrogen-contain
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- Amine compounds, their production and use
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A compound of the formula: STR1 wherein Ar 1 and Ar 2 independently represent an optionally substituted aromatic group; P and Q independently represent a divalent aliphatic hydrocarbon group having at least 2 carbon atoms and optionally having either oxygen or sulfur in the carbon chain; R 1 and R 3 independently represent --CO--R, --CONH--R (R represents a hydrocarbon group or a heterocyclic group) or a hydrocarbon group; R 2 and R 4 independently represent hydrogen or an alkyl group; R 2 and R 4 independently represent hydrogen or an alkyl group; R 1 and R 2 or R 3 and R 4, taken together with the adjacent nitrogen atom, may form a nitrogen-containing heterocyclic group; and j represents 0 or 1, or a salt thereof, has excellent GnRH-receptor antagonizing activity and is useful as a prophylactic and therapeutic agent for hormone-dependent and other diseases.
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