Acta Pharmaceutica (Sep 2017)

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

  • Gündüz Miyase Gözde,
  • Ragno Gaetano,
  • Şimşek Rahime,
  • De Luca Michele,
  • Şafak Cihat,
  • Grande Fedora,
  • El-Khouly Ahmed,
  • İşli Fatma,
  • Yildirim Şeniz,
  • Öztürk Fincan Gökçe Sevim,
  • Ioele Giuseppina

DOI
https://doi.org/10.1515/acph-2017-0026
Journal volume & issue
Vol. 67, no. 3
pp. 341 – 355

Abstract

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This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs) endowed with good muscle relaxant activity and stability to light. Six new condensed DHPs were synthesized by the microwave irradiation method. A long-chain ester moiety [2-(methacryloyloxy)ethyl] and various substituents on the phenyl ring were demonstrated to affect the muscle relaxant activity occurring in isolated rabbit gastric fundus smooth muscle strips. Forced photodegradation conditions were applied to the molecules according to the ICH rules. The degradation profile of the drugs was monitored by spectrophotometry coupled with the multivariate curve resolution technique. Formation of the oxidized pyridine derivative was observed for all the studied DHPs, except for one compound, which showed very fast degradation and formation of a second photo-product. Pharmacological tests on the molecules showed a good muscle relaxing effect, with a mechanism similar to that of nifedipine, however, proving to be more stable to light.

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