PMID: 2754696Aug 1, 1989

Tricyclic compounds as selective muscarinic receptor antagonists. 3. Structure-selectivity relationships in a series of cardioselective (M2) antimuscarinics

Journal of Medicinal Chemistry
W EngelG Trummlitz

Abstract

On the basis of the cardioselective muscarinic receptor antagonist AF-DX 116 (2), a series of 11-substituted pyridobenzodiazepinones (9-35) was prepared and screened for their binding affinity to muscarinic receptors located in cardiac (M2) and glandular (M3) tissue. The ratio of IC50 values of the test compounds in the two different tissues was taken as a measure of cardiac (M2) receptor selectivity. Qualitative structure-selectivity relationships point to the fact that it is the spatial orientation of the protonated side-chain nitrogen atom in relation to the tricycle that is the main determinant for receptor subtype recognition and hence is important for the achievement of cardiac (M2) selectivity.

Citations

Feb 23, 1993·European Journal of Pharmacology·H E ShannonJ S Ward
Feb 12, 2008·Journal of Combinatorial Chemistry·Fuqiang ShiXu Bai
Jul 1, 1991·Journal of Medicinal Chemistry·Y KartonK A Jacobson
Feb 9, 2010·British Journal of Pharmacology·K MohrU Holzgrabe
Mar 25, 2000·Bioorganic & Medicinal Chemistry·J MartinM C Lasne

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