Design, synthesis, and antihypertensive activity of new pyrimidine derivatives endowing new pharmacophores
Journal Article
·
· Medicinal Chemistry Research (Print)
- University of Sadat City, Department of Organic and Medicinal Chemistry, Faculty of Pharmacy (Egypt)
- Damanhour University, Department of Pharmaceutical Chemistry, Faculty of Pharmacy (Egypt)
- Al-Azhar University (Assiut Branch), Department of Pharmacology, Faculty of Medicine (Egypt)
- Assiut University, Department of Histology and Cell Biology, Faculty of Medicine (Egypt)
A new series of achiral pyrimidine derivatives based on nifedipine-like structure was designed and synthesized. These pyrimidyl derivatives contained hydrazine, hydrazones, acetohydrazide, differently substituted benzylidene functionalities, benzosulfohydrazine, various heterocycles such as pyrazole, pyrazolidinedione, thiazoline, and thiazolidinone rings, and fused ring systems such as triazolopyrimidine and pyrimidotriazine rings. Compounds 5a, 5b, 11b, 8b, 9b–d, and 15b showed a decrease in mean arterial rabbit blood pressure (MABP) ranging from 51.4 to 78.2 mmHg in rabbits in comparison with nifedipine-treated rabbits. Among these derivatives, compounds 5a, 5b, 9b, and 9c were found to exhibit calcium channel blockade activity on preparations of rabbit aortae. They exhibited relaxation in the range of 89.2% to 74.4% in comparison to nifedipine (57.6%) as well as a decrease in heart rate. Histopathological effect of compounds 5a,b on the expression of endothelial nitric oxide synthase (eNOS) was also examined on rat aorta. An intense expression of eNOS immune staining in aortic endothelium was seen for compound 5b indicating that it lowered blood pressure via activation of eNOS expression in aorta.
- OSTI ID:
- 22936206
- Journal Information:
- Medicinal Chemistry Research (Print), Journal Name: Medicinal Chemistry Research (Print) Journal Issue: 3 Vol. 28; ISSN 1054-2523
- Country of Publication:
- United States
- Language:
- English
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