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

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GÜNDÜZ M. G., Ragno G., ŞİMŞEK R., De Luca M., Safak C., Grande F., ...More

ACTA PHARMACEUTICA, vol.67, no.3, pp.341-355, 2017 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 67 Issue: 3
  • Publication Date: 2017
  • Doi Number: 10.1515/acph-2017-0026
  • Journal Name: ACTA PHARMACEUTICA
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.341-355
  • Keywords: 1,4-dihydropyridine compounds, muscle relaxant, drug design, structure activity relationship, photostability, MCR analysis, MULTIVARIATE CURVE RESOLUTION, HANTZSCH REACTION, CALCIUM-CHANNEL, FUSED 1,4-DIHYDROPYRIDINES, ANTIHYPERTENSIVES, DERIVATIVES, SPECTROPHOTOMETRY, CYCLODEXTRIN
  • Hacettepe University Affiliated: Yes

Abstract

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 photo degradation 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.