Synthesis and α2-adrenergic activity of 2-[(methyleneamino)oxy]-N-(guanidino)ethaneimines. A bioisosteric replacement of the aryl of guanabenz-type benzylideneaminoguanidine α2-agonists with the [(methyleneamino)oxy]methyl moiety (MAOMM)

Some 2-[(methyleneamino)oxy]-N-(guanidino)ethaneimines were synthesized as analogs of guanabenz-type benzylideneaminoguanidine α2-agonists in which the aryl portion (Ar) is substituted by the [(methyleneamino)oxy]methyl moiety (MAOMM). The α2-adrenergic activity of the synthesized MAOMM derivs. was evaluated by functional tests on guinea-pig ileum. The MAOMM-derivs. exhibited an α2-adrenergic stimulating activity fairly similar to that of the benzylideneaminoguanidine ref. drug guanabenz, thus supporting the hypothesis of the existence of a bioisostere-like relationship between the MAOMM and the Ar in the class of guanabenz-type α2-adrenergic agonists.