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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Design, synthesis and vasorelaxant evaluation of novel coumarin-pyrimidine hybrids
Bioorganic and Medicinal Chemistry, Volume 19, No. 20, Year 2011
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Description
The main objective of the present work depends on the hybridization of coumarin moiety as a vasorelaxant scaffold and pyrimidine ring with known potential cardiovascular activity in order to prepare some new potent antihypertensive candidates. Hence, two groups of pyrimidinyl coumarin derivatives were synthesized and evaluated for their vasorelaxing activity. These compounds were prepared via two routes; either preparation of the guanidinocoumarin 4 followed by a cocktail of cyclization reactions to yield a different array of 6-(substituted pyrimidin-2-yl)aminocoumarins 5-17, or through cyclization of the precursor chalcones 22a-g with guanidine hydrochloride to generate the corresponding final compounds, 8-(6-aryl-2-aminopyrimidin-4-yl)-7- methoxycoumarins 23a-g. The effect of these compounds and the coumarin intermediates 3, 4, 21 and 22a-g on nor-epinephrine induced contracture in thoracic rat aortic rings was investigated using prazocin as reference drug. Several derivatives showed promising activities either equal or even better than that of prazocin (IC 50 0.487 mM). The most prospective compounds; the pyrimidinylamino coumarin derivatives 8, 17 (IC 50 0.411, IC 50 0.421 mM) and the chalcones 22b, 22e (IC 50 0.371, 0.374 mM) that displayed the highest activity can be a base for lead optimization and simple but efficient design of new compounds. 2D-QSAR analysis was applied to find a correlation between the experimental vasorelaxant activities of the newly synthesized coumarin derivatives and their different physicochemical parameters. The result of this study showed that the increase in aqueous solubility while retaining good hydrophobic character of the overall molecule is the key for maintaining high relaxation activity. © 2011 Elsevier Ltd. All rights reserved.
Authors & Co-Authors
Amin, K. M. Mahmoud Y.
Egypt, Cairo
Faculty of Pharmacy
Awadallah, Fadi Mohsen
Egypt, Cairo
Faculty of Pharmacy
Eissa, Amal Abdel Haleem Mohamed
Egypt, Cairo
Faculty of Pharmacy
Abou-Seri, Sahar M.
Egypt, Cairo
Faculty of Pharmacy
Hassan, Ghaneya Sayed
Egypt, Cairo
Faculty of Pharmacy
Statistics
Citations: 54
Authors: 5
Affiliations: 1
Identifiers
Doi:
10.1016/j.bmc.2011.08.037
ISSN:
09680896
e-ISSN:
14643391
Research Areas
Genetics And Genomics
Noncommunicable Diseases
Study Design
Cohort Study