Venous pathology may result from deficiency of the venous wall contractility. The increase in venous system pressure is due to three main factors: increase of Ca 2ϩ concentration in the smooth muscle cells, decrease of endothelial nitric oxide production and decrease of a-adrenergic receptors (a-AR) of the venous system. 1) Our research efforts to find potentially veinotonic molecules were oriented towards aadrenergic compounds, namely a 2-selective agonists, devoid of any vasoconstrictor side-effect due to a 1-AR activation, a 2-AR being relatively more abundant in veins than in arteries. 1-3) Furthermore, low lipophilicity was needed to avoid hematoencephalic resorption and thus to limit the molecules' central effects. It is also well known that imidazoline compounds enhance spontaneous mechanical activity in rat portal vein 4,5) and antagonize the relaxant effects of the K-channel openers. 4-7) Most a 2-adrenergic agonists belong to the classes of aralkylimidazoline and aryliminoimidazolidine derivatives, best represented by clonidine and moxonidine. With the structure-activity relationships of these aryliminoimidazolidine derivatives in mind, 8-11) we kept intact the 2-iminoimidazolidine fragment of the pharmacophore to preserve a good a 2-AR binding and we only modified the aromatic moiety. Among the various structures of the R moiety linked to the imino group (Chart 1) the choice was made between aliphatic moiety and aromatic moiety which could be ortho substituted. We had a special interest in benzopyranic structures because coumarin and flavonoids are usually used as phlebotomic as well as vascular protecting agents. 12-14) Chemistry The final compounds were obtained by condensation of various amines with imidazoline or imidazolidine (Chart 2) bearing adequate leaving groups in position 2 either pre-existent, as methylthio, or formed in situ as chloro. Starting from 2-imidazolidinethione, the hydriodide salt of 2methylmercaptoimidazoline was prepared by the action of iodomethane 15) and was heated with a moderate excess of a primary amine with or without solvent until the evolution of mercaptan was complete 16,17) (method 1). Starting from Nacetylimidazolidin-2-one, 18) the 2-chloro derivative formed in situ with POCl 3 17,19) was condensed with the primary amine and the acetyl protecting group was finally hydrolyzed (method 2). The initial primary amines were commercially available (series A, B) or prepared according to published procedures (series C). 20-27) The structures of all compounds were confirmed by IR, 1 H-NMR, 13 C-NMR and all final imidazolidine compounds were also confirmed by elemental analyses.

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