Collect. Czech. Chem. Commun. 1999, 64, 1457-1470

Fused Thiazoloandrostanes and Their Quaternary Salts, Synthesis and Cooperative Ligand Binding to Muscarinic Acetylcholine Receptor

Marek Urbanskýa,*, Jan Proškab and Pavel Drašara

a Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic
b Research Institute for Pharmacy and Biochemistry, Kouřimská 17, 130 60 Prague 3, Czech Republic


Steroidal thiazolium salts were prepared and their interaction with [3H]N-methylscopolamine ([3H]NMS) at M2 muscarinic receptors using radioligand binding were studied. The results were consistent with a ternary complex theory. The compounds diminished [3H]NMS binding with Kd values in the micromolar or submicromolar range. In particular, the presence of bulky benzylic group at the thiazole nitrogen atom caused a substantial increase in affinity of allosteric ligand for receptor. Our results demonstrate that steroidal thiazolium salts could be a new class of potentially useful tools for mapping the muscarinic receptors.

Keywords: Steroids; Androstane; Thiazoles; Thiazolium salts; Muscarinic receptors; Allosteric ligands.