Enantioselective synthesis and pharmacological evaluation of a new type of verapamil analog with hypotensive and calcium antagonist activities.

Purpose: The syntheses and evaluation for cardiovascular activity in the rat of both enantiomers of a verapamil analog in which the cyano group has been replaced by hydroxyl.

Methods: (+)- and (-)-alpha-[3-[[2-(3,4-Dimethoxyphenyl)ethyl]methylamino]propyl]- 3,4-dimethoxy-alpha-(1-methyl ethyl)benzyl alcohol were prepared from chiral sulfoxides produced by microbial biotransformations using Mortierella isabellina ATCC 42613 or Helminthsporium species NRRL 4671, and were examined for hypotensive and calcium antagonist activity using anaesthetized normotensive rats and isolated rat aorta and atria.

Results: The analogs showed a pharmacological profile similar to that exhibited by verapamil, possessing a remarkable hypotensive activity, accompanied by a significant bradycardia, in anaesthetized normotensive rats.