Antihypertensive activity of newer 1,4-dihydro-5-pyrimidine carboxamides: synthesis and pharmacological evaluation.

A number of 5-(4-substituted phenyl)-2-(substituted benzylsulfanyl)-4-(substituted phenyl)-6-methyl-1,4-dihydro-5-pyrimidine carboxamides (1-30) were designed and synthesized keeping in view the structural requirements as suggested in the pharmacophore model for antihypertensive activity. All the synthesized compounds were tested for antihypertensive activity by non-invasive blood pressure (NIBP) measurements (tail-cuff method) in rats. Almost all the tested compounds displayed considerable decrease in the blood pressure as compared to control. Thirteen compounds showed significant antihypertensive activity comparable to the standard drug nifedipine.

[1]  H. Gavras,et al.  Models of experimental hypertension in mice. , 1996, Hypertension.

[2]  Kazuki Nakamura,et al.  Evaluation of blood pressure measured by tail-cuff methods (without heating) in spontaneously hypertensive rats. , 2006, Biological & pharmaceutical bulletin.

[3]  Rongan Zhang,et al.  Calcium entry blockers and activators: conformational and structural determinants of dihydropyrimidine calcium channel modulators. , 1995, Journal of medicinal chemistry.

[4]  A Hedberg,et al.  Dihydropyrimidine calcium channel blockers. 3. 3-Carbamoyl-4-aryl-1,2,3,4-tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effective antihypertensive agents. , 1991, Journal of medicinal chemistry.

[5]  S. Moreland,et al.  Dihydropyrimidine calcium channel blockers. 4. Basic 3-substituted-4-aryl-1,4-dihydropyrimidine-5-carboxylic acid esters. Potent antihypertensive agents. , 1992, Journal of medicinal chemistry.

[6]  Hsing-I Chen,et al.  A modified technique for tail cuff pressure measurement in unrestrained conscious rats. , 2002, Journal of biomedical science.

[7]  D. Shinde,et al.  Synthesis and anti-inflammatory activity of some [2-amino-6-(4-substituted aryl)-4-(4-substituted phenyl)-1,6-dihydropyrimidine-5-yl]-acetic acid derivatives. , 2003, Acta pharmaceutica.

[8]  H. G. Vogel.  Drug Discovery and Evaluation , 1998 .

[9]  Z. Fortes,et al.  Deoxycorticosterone acetate‐salt hypertensive rats display gender‐related differences in ETB receptor‐mediated vascular responses , 2000, British journal of pharmacology.