Synthesis and Calcium Channel Blocking Activity of 1, 4-Dihydropyridine Derivatives Containing Ester Substitute and Phenyl Carbamoyl Group | Science Publications

American Journal of Applied Sciences

Sigurd Elz¹  Laurentiu Morusciag¹  Bassem Sadek¹  Khairi M.S. Fahelelbom¹ 

关键词: 4-Dihydropyridine Derivatives;    phenyl carbamoyl group;    m-nifedipine;    antihypertensive activity;    Krebs-Henseleit Solution (KHS);    Pentylenetetrazole (PTZ);    Porcine Coronary Artery Smooth Muscles (PCASM);    calcium channel;    antihypertensive drugs;    isolated cardiac;    pressure-induced seizures;    pharmacological observations;   

DOI  :  10.3844/ajassp.2011.303.309

学科分类：自然科学（综合）

来源: Science Publications

【 摘 要 】

Problem statement: Several studies on the synthesis of new nifedipine analogs have beencarried out, but the literature reveled that no study on the synthesis and calcium channel blocking activity ofthe substituted ester with an amide (5-phenylcarbamoyl) moiety has been reported. Approach: Six newderivatives of m-nifedipine have been successfully synthesized by substituting an ester moiety with anamide (5-phenylcarbamoyl) moiety, using a modified Hantzsch reactions and tested for theirpharmacological activities. The nifedipine analogs 1-6 were characterized and confirmed using elementalanalysis, Infrared spectroscopy (IR), Nuclear Magnetic Resonance (¹H NMR) and Mass spectroscopy. Thepurity of the compounds was ascertained by melting point and TLC. The in vitro calcium channel blockingactivities were evaluated using the high K⁺ concentration of Porcine Coronary Artery Smooth Muscles(PCASM) assay. Results: The compounds (1-2) failed to exhibit any blocking activity (IC50 = 10^?7 to 10^?5M range), while the compounds 3-6 relaxed precontracted porcine coronary artery smooth muscles withpEC50 values ranging between 4.37±0.10 (compound 3) and 6.46±0.07 (compound 5), indicating thatcompounds 3-6 exhibit comparable potencies in blocking calcium channels to reference drug varapamil(6.97±0.15) and m-nifedipine (6.48±0.05). Conclusion: The results of this study showed that some of thedeveloped new compounds possess maximal calcium channel blocking effects comparable to m-nifedipine.The developed compounds in the present study will predicatively show an increased metabolic stability andconsequently longer duration of actions compared to m-nifedipine and could be, therefore, suitablecandidates for further optimization to be evaluated as a new class of antihypertensive drugs.

【 授权许可】

Unknown