二恶烷和氧硫杂环戊烷核：毒蕈碱激动剂的合适亚结构。

Dioxane and oxathiane nuclei: suitable substructures for muscarinic agonists.

作者信息

Piergentili Alessandro, Quaglia Wilma, Giannella Mario, Del Bello Fabio, Bruni Bruno, Buccioni Michela, Carrieri Antonio, Ciattini Samuele

机构信息

Dipartimento di Scienze Chimiche, Università degli Studi di Camerino, Via S. Agostino, 1, 62032 Camerino, Italy.

出版信息

Bioorg Med Chem. 2007 Jan 15;15(2):886-96. doi: 10.1016/j.bmc.2006.10.040. Epub 2006 Oct 21.

DOI:10.1016/j.bmc.2006.10.040

PMID:17084634

Abstract

Muscarinic agonists, bearing 1,4-dioxane and 1,4-oxathiane nuclei, were synthesized and tested to evaluate their potency at M(1)-M(4) muscarinic receptor subtypes. The stereochemical relationship between the 2-side chain and the 6-methyl group plays an important role in drug-receptor interaction, since the cis isomers are more potent than the corresponding trans isomers. However, the latter are able to discriminate between the muscarinic receptor subtypes. Among them compound 5b proves particularly interesting, since it selectively activates the ileal M(3) receptor subtype and is devoid of agonist activity at the others.

摘要

合成了带有1,4 - 二氧六环和1,4 - 氧硫杂环已烷核的毒蕈碱激动剂，并对其进行测试以评估它们对M(1)-M(4)毒蕈碱受体亚型的效力。2 - 侧链与6 - 甲基之间的立体化学关系在药物 - 受体相互作用中起重要作用，因为顺式异构体比相应的反式异构体更有效。然而，后者能够区分毒蕈碱受体亚型。其中化合物5b特别有趣，因为它选择性地激活回肠M(3)受体亚型，而在其他受体亚型上没有激动剂活性。