Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds

This paper describes the synthesis of 1,4-dihydropyridinecompounds (DHPs) endowed with good muscle relaxantactivity and stability to light. Six new condensed DHPswere synthesized by the microwave irradiation method. Along-chain ester moiety [2-(methacryloyloxy)ethyl] andvarious substituents on the phenyl ring were demonstratedto aff ect the muscle relaxant activity occurring in isolatedrabbit gastric fundus smooth muscle strips. Forced photodegradationconditions were applied to the molecules accordingto the ICH rules. The degradation profi le of thedrugs was monitored by spectrophotometry coupled withthe multivariate curve resolution technique. Formation ofthe oxidized pyridine derivative was observed for all thestudied DHPs, except for one compound, which showedvery fast degradation and formation of a second photoproduct.Pharmacological tests on the molecules showed agood muscle relaxing eff ect, with a mechanism similar tothat of nifedipine, however, proving to be more stable tolight.