Synthesis and Muscarinic Activity of a Series of Quinolines and Naphthalenes with a 1-Azabicyclo[3.3.0]octane Moiety

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概要

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• In order to discover a medicine effective against Alzheimer's disease, we synthesized a series of quinoline derivatives having a characteristic 1-azabicyclo[3.3.0]octane amine ring, and performed pharmacological evaluation of them. Acetylcholine esterase inhibitory activities of these derivatives were unexpectedly weak. Tests for central nervous muscarinic cholinergic receptor binding affinity indicated that these compounds had higher affinities to muscarinic M1 receptors than to M2 receptors.A series of naphthalene derivatives substituted with the 1-azabicyclo[3.3.0]octane ring were also synthesized and muscarinic M1 and M2 receptor binding affinity deterimned. These compounds had much higher affinity for M1 receptors than the quinoline derivatives, and 1-[N-(1-azabicyclo[3.3.0]octan-5-yl)methyl-N-methylamino]-4-nitronaphthalene showed the highest affinity and selectivity. The ability of this compound to improve cognitive function was assessed using the passive avoidance test in scopolamine-induced mice.

• 公益社団法人日本薬学会の論文
• 1998-08-15

著者

• KATAOKA Tadashi

  Gifu Pharmaceutical University

• SUZUKI Tomoo

  Drug Discovery Research Department, Sanwa Kagaku Kenkyusho Co., Ltd.,

• Usui Toshinao

  Drug Discovery Research Department Sanwa Kagaku Kenkyusho Co. Ltd.

• OKA Mitsuru

  Drug Discovery Research Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd.,

• SUZUKI Tsunemasa

  Drug Development Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd.,

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