STRUCTURAL STUDY OF 3,4-DIHYDROPYRIDONES AND FURO[3,4-B]-2(1H)-PYRIDONES AS POTENTIAL CALCIUM-CHANNEL MODULATORS

A structural study of 4-aryl substituted 5-alkoxycarbonyl-6-methyl-3,4 -dihydropyridones (4a-d) and hexahydrofuro-[3,4-b]-2-(1H)-pyridones (5 a-d) has been carried out using X-ray analyses, semiempirical (AM1) ca lculations, NOE experiments and coupling constants. From the two favou red conformers (A and B), conformation A bearing the phenyl ring in a pseudoaxial position turned out to be the most stable both in the soli d state and in solution. Compounds 4a-d fulfil, from the structural po int of view, all the requirements needed for exhibiting an antagonist calcium effect and an agonist effect should be expected for compounds 5a-d. (C) 1998 Published by Elsevier Science Ltd. All rights reserved.