Synthesis of (1-azabicyclo[3.3.0]octanyl)methyl-substituted aromatic heterocycles and their muscarinic activity.
In our development of drugs effective against Alzheimer's disease, we have researched a series of aromatic compounds having a characteristic cyclic amine, 1-azabicyclo[3.3.0]octane ring. In this report, we describe synthesis of a series of aromatic heterocycles with the 1-azabicyclo[3.3.0]octane ring and their pharmacological evaluation. 3-Amino-5-(1-azabicyclo[3.3.0]octan-5-yl)methyl-1,2,4-oxadiazole (2b) showed the highest M1 selectivity.
Suzuki
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Drug Discovery Research Laboratory, Sanwa Kagaku Kenkyusho Co., Ltd., Mie, Japan.
Uesaka
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Hamajima
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Ikami
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D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology; D010890:Pirenzepine / Q000493:pharmacokinetics; D011813:Quinuclidinyl Benzilate / Q000493:pharmacokinetics; D051381:Rats; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic / Q000187:drug effects; D012601:Scopolamine / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology
C067766:2,8-dimethyl-3-methylene-1-oxa-8-azaspiro(4,5)decane; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018727:Muscarinic Antagonists; D010277:Parasympathomimetics; D043643:Receptor, Muscarinic M1; D043585:Receptor, Muscarinic M2; D011976:Receptors, Muscarinic; D013141:Spiro Compounds; D010890:Pirenzepine; D011813:Quinuclidinyl Benzilate; D012601:Scopolamine