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Synthesis and investigation of antihypertensive activity using anaesthetizednormotensive nonhuman primates of some 2-aryl-4-(substituted) pyrimido [1,2-a] benzimidazoles | Abstract

Der Pharma Chemica
Journal for Medicinal Chemistry, Pharmaceutical Chemistry, Pharmaceutical Sciences and Computational Chemistry

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Abstract

Synthesis and investigation of antihypertensive activity using anaesthetizednormotensive nonhuman primates of some 2-aryl-4-(substituted) pyrimido [1,2-a] benzimidazoles

Author(s): Abdel-Nasser A. El-Shorbagi and Mostafa A. Husein

In this work, we studied the in vivo pharmacological effects of the new derivatives related to fused [6-5-6] system, pyrimido-benzimidazole and compared with those of tolazoline. In anaesthetized normotensive dogs, both 6d and tolazoline (10-3 mmole/kg, iv) caused a pronounced fall in mean blood pressure as hypotensive agents. Upon investigating the antihypertensive activity of 6d, it markedly inhibited the hypertensive effect of noradrenaline. The required new pyrimido [l,2-a] benzimidazole derivatives were synthesized from precursors 1-3. Compounds 1-3 intern obtained from condensing 2-aminobenzimidazole with beta-diketones which were then condensed with the appropriate aldehyde 4a-f to produce three series: 5a-f, 6a-f and 7a-f. The products are obtained in moderate yields and are in trans [E]-configuration. The structure of the synthesized derivatives has been characterized by elemental microanalysis (CHN), IR and NMR Spectroscopy, as well as physicochemical properties. The geometry of the alkene resulted from condensation was verified by IR. In conclusion: Pyrimido-benzimidazole scaffold is a good target for further search for antihypertensive agents.


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