GB1110099A — Urea and thiourea derivatives

USPTO Abstract

Novel urea and thiourea derivatives of Formula I <FORM:1110099/C2/1> wherein X is oxygen or sulphur, A is a straight or branched alkylene group having 1-4 carbon atoms, the groups -NH- and -CO-attached to a common benzene nucleus are in meta or para position in relation to one another, R and R1 are hydrogen or methyl, and the groupings -NH- and -CH3 attached to a common benzene nucleus are in ortho position in relation to one another, and acid addition salts thereof, are prepared by reacting two moles of an amino-amidine of Formula II <FORM:1110099/C2/2> or an acid addition salt thereof, with one mole of carbonyldiimidazole or thiocarbonyldiimidazole, with or without an inert and anhydrous organic solvent at a temperature between ambient and 120 DEG C., or by reacting one mole of a 1,3-bis-(3-chlorocarbonylphenyl)-urea or -thiourea with two moles of an aminoamidine of formula <FORM:1110099/C2/3> and, in each case, optionally converting the product obtained into an acid addition salt. The starting materials of Formula II may be prepared by the series of reactions shown in the following reaction scheme: <FORM:1110099/C2/4> The bis(3-chlorocarbonylphenyl)-ureas or thioureas may be prepared by treating the corresponding diacid obtained by reacting amino-benzoic acid with urea, with thionyl chloride. The amidines of Formula II may also be prepared by treating a (nitrobenzamido)-benzoic acid with thionyl chloride, reacting the acid chloride with an aminonitrile, treating the [(nitrobenzamido)-benzamido]-nitrile with dry gaseous hydrogen chloride in chloroform/ethanol, isolating the imino-ether hydrochloride and treating this with anhydrous ammonia at 0 DEG C. to give the [(nitrobenzamido)benzamido]-amidine which is then hydrogenated. Therapeutic compositions having anti-viral and hepatoprotective activity, which may be administered parenterally, or orally, contain as active ingredient at least one compound of Formula I above or a non-toxic acid addition salt thereof.