Correlations of antihypertensive and antisecretory activities with various structural modifications of the antihypertensive agent clonidine (2-(2,6-dichlorophenylimino)imidazolidine) are described. Eleven chemical classes of compounds containing an "amidine" moiety were prepared in this study. The antihypertensive activity of these compounds was evaluated in metacorticoid hypertensive rats and unanesthetized neurogenic hypertensive dogs following oral administration. Antisecretory activity was evaluated in fistula rats by measuring pH and volume of gastric secretion. Two compounds, 2-(2,6-dimethylphenylimino)imidazolidine and 2-(2,6-dichlorophenylimino)pyrrolidine, are particularly effective antisecretory agents with minimal antihypertensive activity.

Amidines was warmed on a steam bath for 2 hr. The volatiles were removed under reduced pressure and the residue was taken up in 5% aqueous HCI and washed with Et20. Excess K2C03 was added and the product extracted (Et20), dried (Na2S04), and treated with Et20-HCI. The salt was recrystallized twice from Me,CO to afford 4.3 g (73%) of product: mp 160-161°; ir (KBr) 1770 (ester 0=0); nmr (D,0) 2.40 (s 6, CH3COOAr), 2.95 (s, 6, N(CH3)2), 3.25 (m, 4, CHjCHj), 7.30 (m, 3, Ar H). Anal. (C14H20NO4Cl) C, , N.

Aus den Isothioharnstoffäthern (I) und Aminoacetaldehydacetal (II) entstehen die Kondensate (III), die mit HCl zu (IV) und (V) cyclisiert werden.

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