Nelson W L, Freeman D S, Vincenzi F F
J Med Chem. 1976 Jan;19(1):153-8. doi: 10.1021/jm00223a026.
Preparation of analogs of 4-[N-(3-chlorophenyl) carbamoyloxy]-2-butynyltrimethylammonium chloride [1 (McN-A-343)], cis- and trans-4-[N-(4-chlorophenyl)carbamoyloxy]-2-butenyltrimethylammonium iodides (5 and 6), and the corresponding epoxides and cyclopropanes is reported. Pharmacological testing for ganglion-stimulating activity demonstrated that the trans olefin 6 and trans epoxide 8 have properties similar to 1, while the trans cyclopropane analog 10 was inactive. All cis compounds were inactive. The muscarinic ganglion-stimulating properties of the active compounds are interpreted in terms of similar fit at the receptor level by the alkyltrimethylammonium ion and the ether oxygen 5.7 A distant, as well as an electron-rich center midway between groups in the form of a double bond or unshared electron pairs. Comparison of smooth muscle and ganglion-stimulating properties of the compounds showed that trans epoxide 8 was the most selective for muscarinic ganglionic sites.
报道了4-[N-(3-氯苯基)氨基甲酰氧基]-2-丁炔基三甲基氯化铵[1 (McN-A-343)]、顺式和反式4-[N-(4-氯苯基)氨基甲酰氧基]-2-丁烯基三甲基碘化铵(5和6)以及相应的环氧化物和环丙烷类似物的制备。对神经节刺激活性的药理学测试表明，反式烯烃6和反式环氧化物8具有与1相似的性质，而反式环丙烷类似物10无活性。所有顺式化合物均无活性。活性化合物的毒蕈碱神经节刺激特性可通过烷基三甲基铵离子和相距5.7 Å的醚氧在受体水平上的相似契合以及以双键或未共享电子对形式存在于基团之间的富电子中心来解释。化合物平滑肌和神经节刺激特性的比较表明，反式环氧化物8对毒蕈碱神经节部位具有最高的选择性。
