STEREOCHEMICAL STUDY OF A BRADICARDISANT BENZAZEPINE-TYPE DRUG - X-RAY STRUCTURE OF THE CHLORIDE SALT AND HIGH-FIELD NMR-STUDY OF THE STEREOCHEMISTRY IN SOLUTION

A chiral bradicardisant benzazepine-type drug with an asymmetric carbo n and a tertiary amino nitrogen was studied as the chloride salt, X-ra y analysis in the solid state of the salt formed upon protonation of t he base shows the occurrence in the unit cell of two diastereomeric sp ecies with horseshoe-shaped structures, NMR parameters were obtained f or the base and for the protonated species in solution, A conformation al study by 20 NOESY and ROESY NMR techniques led to the conclusion th at conformations similar to the solid-state structures were retained i n solution, Over a wide range of pH, in particular in alkaline solutio n or under biological conditions, a conformation similar to that of th e 1'(R) N(R) diastereomer is observed, The diastereomeric species 1'(R ) N(R) and 1'(R) N(S) were clearly identified at low pH values with co nformations similar to their solid-state structures. (C) 1997 by John Wiley & Sons, Ltd.