Microwave-assisted synthesis of condensed 1,4-dihydropyridines as potential calcium channel modulators


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Ozer E. K., GÜNDÜZ M. G., El-Khouly A., SARA M. Y., ŞİMŞEK R., İSKİT A. B., ...More

TURKISH JOURNAL OF CHEMISTRY, vol.39, no.4, pp.886-896, 2015 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 39 Issue: 4
  • Publication Date: 2015
  • Doi Number: 10.3906/kim-1412-72
  • Journal Name: TURKISH JOURNAL OF CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, TR DİZİN (ULAKBİM)
  • Page Numbers: pp.886-896
  • Hacettepe University Affiliated: Yes

Abstract

This study reports the design, synthesis, and calcium channel modulatory activity evaluation of a series of 14 novel fused 1,4-dihydropyridine derivatives. The molecular design of the compounds was based on modifications of nifedipine, which is a calcium channel blocker. The compounds were achieved by one-pot microwave-assisted reaction of 4,4-dimethyl-1,3-cyclohexanedione, 5-chlorosalicylaldehyde/3,5-dichlorosalicylaldehyde, an appropriate alkyl acetoacetate, and ammonium acetate in ethanol according to a modified Hantzsch reaction. The structures of the compounds were confirmed by spectral methods and elemental analysis. To evaluate their relaxant activities, the maximum relaxant response (E-max) and pD(2) values of the compounds and nifedipine were determined on isolated rat aorta rings. The obtained results indicated that all compounds produced concentration-dependent relaxation on the rings possibly due to the blockade of calcium channels. The E-max values (a measure of efficacy) of five compounds were higher than those of nifedipine.