ORIGINAL ARTICLE
Year : 2013  |  Volume : 12  |  Issue : 1  |  Page : 20-27

Synthesis and antihypertensive activity of certain substituted dihydropyridines and pyrimidinones


1 Department of Chemistry of Natural and Microbial Products, National Research Centre, Giza, Egypt
2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Giza, Egypt

Correspondence Address:
Hanaa A. Tawfik
PhD, Department of Chemistry of Natural and Microbial Products, National Research Centre, Dokki, Giza 12311
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.7123/01.EPJ.0000426587.41764.d4

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Background and objective

Some bulky substituted aromatic aldehydes reacted with urea and ethyl acetoacetate in the presence of acetic acid as a catalyst to yield solely substituted dihydropyridines (Hantzsch-type molecule). In the presence of p-toluene sulfonic acid as a catalyst, the products were only dihydropyrimidines (Biginelli compounds). The same aldehydes yielded dihydropyrimidinones on using acetyl acetone instead of ethyl acetoacetate whatever the catalyst used. These two classes of molecules represent a heterocyclic system of a remarkable antihypertensive effect. The aim of this study was to synthesize certain dihydropyridine and pyrimidinone derivatives with aromatic moiety with bulky substituents to be evaluated for their antihypertensive effect.

Methods

The aldehydes 3-(substituted-phenyl)-1-phenyl-1H-pyrazole-4-carbaldehyde 35, 4-oxo-4H-chromene-3-carbaldehyde (6), and substituted phenylazo-benzaldehyde 79 reacted with ethyl acetoacetate and urea in ethanol in the presence of acetic acid to yield dihydropyridines 1015. Aldehydes 39 reacted with ethyl acetoacetate and urea in the presence of p-toluene sulfonic acid to yield dihydropyrimidinones 1622. Furthermore, the reaction of the aldehydes 39 with ethyl acetoacetate and urea in the presence of either acetic acid or p-toluene sulfonic acid yielded the corresponding dihydropyrimidinones 2329.

Results and conclusion

The hypotensive activity of compounds 1014 and 1620 indicated that the 4-aryl-dihydropyridine derivatives 1014 showed higher activity than the pyrimidinones 1620. The most active compound was 4-(1,3-diphenyl-1H-pyrazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid diethyl ester (10) at dose levels of 0.6, 1.2, and 2.4 mg/kg. It showed more or less similar hypotensive activity as the reference drug nifedipene at doses of 1.2 and 2.4 mg/kg. Its LD50=298 mg/kg body weight.



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