CONFORMATIONAL-ANALYSIS AND INOTROPIC ACTIVITY OF 2-SUBSTITUTED-5-CYANO-1,6-DIHYDRO-6-OXO-3-PYRIDINE CARBOXYLATES .2.

Single-crystal X-ray work has been carried out on the benzyl-5-cyano-1 ,6-dihydro-6-oxo-3-methoxycarbonyl pyridine compound 1f. It crystalliz es in the triclinic system space group P1BAR. Minimum energy conformat ions of 2-(alkyl or arylalkyl) 5-cyano-1,6-dihydro-6-oxo-3-pyridine ca rboxylates showing different biological activity have been calculated by the semiempirical MNDO and AMI methods. A most critical factor for the different inotropic activities (positive or negative) of compounds 1a - 1f seems to be related to the location and the steric requiremen ts of a 'pocket' in the receptor boundary that limit the size of the s ubstituent at position 2.