In this manuscript, we investigated-in vivo- the hypotensive activity of the new derivatives related to the scaffold pyrimido-benzimidazole and compared the results with tolazoline. All of the reference; tolazoline and the tested derivatives are introduced in equimolar ratios in doses of (0.1 mg/kg iv) using anaesthetized-normotensive nonhuman primates (dogs). The new pyrimido [l,2-a] benzimidazole derivatives were synthesized from 2,4-dimethylpyrimido [1,2-a] benzimidazole (1) which intern, obtained from condensing 2-aminobenzimidazole with acetylacetone. Precusor 1 was then condensed with the appropriate aldehyde 2a-f to produce two series: 3a-f, and 4a-f, as trans [E]-configurational geometry. The structure of the synthesized derivatives has been characterized by elemental microanalysis (CHN), IR, MS and NMR Spectroscopy, as well as physicochemical properties. In conclusion: Pyrimido-benzimidazole scaffold is a good target for antihypertensive activity.