Romanelli M N, Gualtieri F, Valle G, Brasili L, Angeli P
Dipartimento di Scienze Farmaceutiche, Firenze, Italy.
J Med Chem. 1988 Sep;31(9):1703-8. doi: 10.1021/jm00117a007.
The four isomers of 2-cyclohexyl-2-phenyl-5-[(dimethylamino)methyl] -1,3-oxathiolane methiodide were prepared. Their absolute configuration was attributed by means of X-ray crystallography and circular dichroism. The compounds were tested on rat bladder and guinea pig ileum and heart, and their antimuscarinic potency was evaluated and expressed as pA2. The results show that the introduction of a chiral center into position 2 brings about a small but definite enantioselectivity on rat bladder and guinea pig ileum which is not seen for guinea pig heart. This supports the view that differences exist among the muscarinic receptors of these tissues (M2 receptors). Comparison of the absolute configuration of the antagonists studied in this and in the preceding paper2 and that of strictly related agonists supports the hypothesis of a common binding site for agonists and antagonists of this kind.
制备了2-环己基-2-苯基-5-[(二甲氨基)甲基]-1,3-氧硫杂环戊烷甲碘化物的四种异构体。通过X射线晶体学和圆二色性确定了它们的绝对构型。在大鼠膀胱、豚鼠回肠和心脏上对这些化合物进行了测试，并评估了它们的抗毒蕈碱效力，以pA2表示。结果表明，在2位引入手性中心会对大鼠膀胱和豚鼠回肠产生微小但确定的对映体选择性，而在豚鼠心脏中未观察到这种情况。这支持了这些组织的毒蕈碱受体（M2受体）之间存在差异的观点。将本文及前文[2]中研究的拮抗剂的绝对构型与严格相关的激动剂的绝对构型进行比较，支持了这类激动剂和拮抗剂具有共同结合位点的假设。
