Acta Pharm. 67 (2017) 341-355

 

full paper

Original research paper

 

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

MIYASE GÖZDE GÜNDÜZ, GAETANO RAGNO, RAHIME ŞIMŞEK, MICHELE DE LUCA, CIHAT ŞAFAK, FEDORA GRANDE, AHMED EL-KHOULY, FATMA İŞLI, ŞENIZ YILDIRIM, GÖKÇE SEVIM ÖZTÜRK FINCAN and GIUSEPPINA IOELE

giuseppina.ioele@unical.it

1 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, 06100, Ankara, Turkey

2 Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende (CS), Italy

3 Department of Pharmacology, Faculty of Medicine, Gazi University, 06560, Ankara, Turkey

Accepted May 10, 2017

Published online June 14, 2017

 

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 photoproduct. 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.

 

Keywords: 1,4-dihydropyridine compounds, muscle relaxant, drug design, structure activity relationship, photostability, MCR analysis