Journal of the Iranian Chemical Society

, Volume 4, Issue 1, pp 30–36 | Cite as

Synthesis and calcium channel antagonist activities of new derivatives of dialkyl 1,4-dihydro-2,6-dimethyl-4-(5-phenylisoxazol-3-yl)pyridine-3,5-dicarboxylates

  • N. Daryabari
  • T. Akbarzadeh
  • M. Amini
  • R. Miri
  • H. Mirkhani
  • A. Shafiee
Article

Abstract

The new analogues of nifedipine, in which 2-nitrophenyl group at position 4 is replaced by phenylisoxazolyl substituent, were synthesized. The symmetrical dialkyl 1,4-dihydro-2,6-dimethyl-4-(5-phenylisoxazol-3-yl)pyridine-3,5-dicarboxylates were prepared by classical Hantzsch condensation, and the asymmetrical analogues were synthesized using a procedure reported by Dagnino that involved the condensation of alkyl acetoacetate with alkyl 3-aminocrotonate and 5-phenylisoxazole-3-carboxaldehyde. The structure of all compounds was confirmed by IR, 1H NMR and Mass spectra. In vitro calcium channel antagonist activities were evaluated as calcium channel antagonists using the high K+ concentration of guinea-pig ileum longitudinal smooth muscle (GPILSM) assay. These compounds exhibited moderate calcium antagonist activity (IC50 = 10−7 to 10 5 M range) relative to the reference drug nifedipine (IC50 = 1.10 ± 0.40 × 10−8 M).

Keywords

Dihydropyridine Ca2+ channels antagonist Phenylisoxazole 

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Copyright information

© Iranian Chemical Society 2007

Authors and Affiliations

  • N. Daryabari
    • 1
  • T. Akbarzadeh
    • 1
  • M. Amini
    • 1
  • R. Miri
    • 1
    • 2
  • H. Mirkhani
    • 2
  • A. Shafiee
    • 1
  1. 1.Department of Medicinal Chemistry, Faculty of PharmacyTehran University of Medical ScienceTehranIran
  2. 2.Medicinal & Natural Product Chemistry Research CentreShiraz University of Medical ScienceShirazIran

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