Synthesis and calcium channel blocking activity of 1, 4-dihydropyridine derivatives containing ester substitute and phenyl carbamoyl group

Bassem Sadek, Khairi Mustafa Salem Fahelelbom, Laurentiu Morusciag, Sigurd Elz

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Problem statement: Several studies on the synthesis of new nifedipine analogs have been carried out, but the literature reveled that no study on the synthesis and calcium channel blocking activity of the substituted ester with an amide (5-phenylcarbamoyl) moiety has been reported. Approach: Six new derivatives of m-nifedipine have been successfully synthesized by substituting an ester moiety with an amide (5-phenylcarbamoyl) moiety, using a modified Hantzsch reactions and tested for their pharmacological activities. The nifedipine analogs 1-6 were characterized and confirmed using elemental analysis, Infrared spectroscopy (IR), Nuclear Magnetic Resonance (1H NMR) and Mass spectroscopy. The purity of the compounds was ascertained by melting point and TLC. The in vitro calcium channel blocking activities 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 10-5 M range), while the compounds 3-6 relaxed precontracted porcine coronary artery smooth muscles with pEC50 values ranging between 4.37±0.10 (compound 3) and 6.46±0.07 (compound 5), indicating that compounds 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 the developed 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 and consequently longer duration of actions compared to m-nifedipine and could be, therefore, suitable candidates for further optimization to be evaluated as a new class of antihypertensive drugs.

Original languageEnglish
Pages (from-to)303-309
Number of pages7
JournalAmerican Journal of Applied Sciences
Volume8
Issue number4
DOIs
Publication statusPublished - 2011
Externally publishedYes

Keywords

  • 4-Dihydropyridine Derivatives
  • Antihypertensive activity
  • Antihypertensive drugs
  • Calcium channel
  • Isolated cardiac
  • Krebs-Henseleit Solution (KHS), Pentylenetetrazole (PTZ), Porcine Coronary Artery Smooth Muscles (PCASM)
  • M-nifedipine
  • Pharmacological observations
  • Phenyl carbamoyl group
  • Pressure-induced seizures

ASJC Scopus subject areas

  • General

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