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Article info. : 2007; 4(1) (pp 30~36)

 

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 a, T. Akbarzadeha, M. Aminia, R. Miri a,b, H. Mirkhani b and A. Shafieea,*

aDepartment of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, 14174, IranbMedicinal & Natural Product Chemistry Research Centre, Shiraz University of Medical Science, Shiraz, Iran

(Received 28 January 2007, Accepted 3 February 2007)

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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