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Absolute configuration and biological activity of mequitamium iodide enantiomers
Author(s) -
Di Bugno Cristina,
Dapporto Paolo,
Giorgi Raffaello,
Manzini Stefano,
Paoli Paola,
Subissi Alessandro,
Arcamone Federico
Publication year - 1994
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530060505
Subject(s) - chemistry , enantiomer , absolute configuration , stereochemistry , conformational isomerism , molecular model , octane , iodide , phenothiazine , methyl iodide , molecule , medicinal chemistry , organic chemistry , medicine , pharmacology
The enantiomers of 1‐methyl‐3‐(10 H ‐phenothiazine‐10‐ylmethyl)‐1‐azoniabicyclo[2,2,2]octane iodide ( 1 ) were prepared by chiral chromatographic resolution of the precursor mequitazine ( 2 ). The (+)‐(S)‐enantiomer 1b is 10‐fold more potent than (−)‐(R)‐enantiomer 1a as a histamine antagonist, while the two enantiomers show the same antimuscarinic activity in vitro. The absolute configuration of the more active dextrorotatory isomer has been determined by X‐ray analysis. Conformational analysis and molecular modeling suggest that the (+)‐(S)‐enantiomer can adopt a conformation similar to that attributed to the receptor binding conformers of classical antihistamines. © 1994 Wiley‐Liss, Inc.