<abstract xmlns="http://www.w3.org/1999/xhtml"><p>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.</p></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 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.

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

Department of Pharmaceutical Chemistry, Faculty of Pharmacy

Department of Pharmacy, Health and Nutritional Sciences

Department of Pharmacology, Faculty of Medicine

Acta Pharmaceutica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs) endowed with good muscle relaxant activity and stability to light. Six new condensed...

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

Published Online: Aug 30, 2017

Page range: 341 - 355

Accepted: May 10, 2017

DOI: https://doi.org/10.1515/acph-2017-0026

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

© 2017 Miyase Gözde Gündüz et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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

Published Online: Aug 30, 2017

Page range: 341 - 355

Accepted: May 10, 2017

DOI: https://doi.org/10.1515/acph-2017-0026

Keywords1,4-dihydropyridine compounds, muscle relaxant, drug design, structure activity relationship, photostability, MCR analysis

© 2017 Miyase Gözde Gündüz et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

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