Molecular geometries of dibenzothiazepinone and dibenzoxazepinone calcium antagonist

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TypeArticle
Journal titleDrug Design and Discovery
ISSN1055-9612
Volume12
Issue4
Pages337358
AbstractA no. of dibenzothiazepinones and dibenzoxazepinones have been designed, synthesized and evaluated as calcium antagonists. Mol. geometries of these dibenzotricyclic calcium antagonists have been studied using x-ray crystallog., mol. modeling and two-dimensional NMR spectroscopy. X-ray diffraction reveals dibenzothiazepinoine I (X = S) and dibenzoxazepinone I (X = O) to have, resp., flexure angles of 108° and 116.9° between the two benzene rings. The mol. mechanics-optimized geometry of dibenzothiazepinone I (X = S) shows a 7° smaller flexure angle than the x-ray crystallog. result, while that of dibenzoxazepinone I (X = O) has an angle only 2° smaller than the x-ray result. AM1 and ab initio calcns. show that the side chains can affect the geometry of the tricyclic nucleus and both I (X = S, O) have neg. electrostatic potentials around the bridged portion of the tricyclics. Two-dimensional NOESY NMR spectroscopy supports the extended geometry of the 6 carbon spacer as obtained from x-ray crystallog. and mol. mechanics calcns. Vasorelaxation properties among these compds. appear to be relatively insensitive to the flexure angle and to chain length. Vasorelaxation is profoundly influenced by the nature of the basic terminal moiety.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada; NRC Institute for Biodiagnostics; NRC Institute for Marine Biosciences
Peer reviewedYes
NPARC number23000893
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Record identifier17abc9d6-282f-4f79-aea9-775834fdf2cd
Record created2016-11-07
Record modified2016-11-07
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