Giannella M, Piergentili A, Pigini M, Quaglia W, Rafaiani G, Tayebati S K
Dipartimento di Scienze Chimiche, Università di Camerino, Italy.
Chem Pharm Bull (Tokyo). 1994 Jun;42(6):1286-90. doi: 10.1248/cpb.42.1286.
To acquire more information about the so-called "muscarinic subsite", compound 4 was synthesized and tested. The results show that in comparison with deoxamuscarine (23) the muscarinic potency of 4 on M2 and M3 subtypes is not significantly altered by the presence of an epoxidic function, which confirms the donor-acceptor hydrogen bonding character of this receptive site. Conversely, there is a negative influence on the transduction processes. In addition, a second hydroxylic function bound on the carbon carrying the terminal methyl of the fourth substituent on the nitrogen dramatically affects the muscarinic behavior; the resulting compounds (11-14) lack any agonist or antagonist activity.
为了获取更多关于所谓“毒蕈碱亚位点”的信息，合成并测试了化合物4。结果表明，与去氧毒蕈碱（23）相比，4对M2和M3亚型的毒蕈碱活性在环氧功能存在时没有显著改变，这证实了该受体位点的供体-受体氢键特性。相反，对转导过程有负面影响。此外，与氮上第四个取代基末端甲基相连的碳原子上连接的第二个羟基功能显著影响毒蕈碱行为；所得化合物（11 - 14）缺乏任何激动剂或拮抗剂活性。
