GB1456257A - 2-aminothiazole derivatives - Google Patents

Abstract

1456257 2 - Aminothiazole derivatives CENTRE D'ETUDES POUR L'INDUSTRIE PHARMACEUTIQUE 15 May 1974 [16 May 1973] 21614/74 Heading C2C Novel 2-aminothiazole derivatives of the general formula wherein R is a group of formula or linked with the sulphur atom by its central carbon atom: R 1 and R 2 , which may be the same or different, are hydrogen atoms or alkenyl, alkyl, cycloalkyl, aryl or aralkyl groups (which groups may optionally be substituted by halogen atoms or hydroxy groups), or form, together with the nitrogen atom to which they are linked, a saturated heterocyclic ring having 4 to 8 ring members and optionally containing a nitrogen, oxygen, or sulphur atom as a second heteroatom and being optionally substituted by an alkyl group; and R 3 and R 4 , which may be the same or different, are hydrogen atoms or alkyl or cycloalkyl groups, or form, together with the nitrogen atom to which they are linked, a saturated heterocyclic ring having 5 or 6 ring members and optionally containing oxygen, nitrogen, or sulphur as a second hetero-atom which (in the case of nitrogen) is optionally substituted by an aryl, haloaryl, alkoxyaryl, alkyl, hydroxyalkyl, haloalkyl, alkoxy, trifluoromethyl or halohydroxyalkyl group; and the mineral and organic acid addition and quaternary ammonium salts thereof are prepared by reacting AH with BNCS. (A being -NR 1 R 2 when B is -CH 2 -R 0 -CH 2 -NR 3 R 4 and, when R 2 is H, being when B is R 1 , R 0 being -CH = CH- or -C # C-) and cyclizing the resulting thiourea of the general formula by heating in an acid medium to form a thiazoline of the general formula wherein R is (b) above, when R 0 is -CH = CH-, or (a) above linked to the N atom by the C atom which is not adjacent to its double bond, when R 0 is -C # C-, and optionally isomerizing the thiazoline obtained in which R is (a) above by heating in solution at above 100‹ C. or treating with concentrated acid to form a thiazole of the first general formula above wherein R is linked to the N atom by the C atom adjacent to its double bond; followed optionally by salification. Isothiocyanates of the general formula are prepared by treating with CS 2 in the presence of cyclohexylcarbodiimide at a low temperature in a solvent. Pharmaceutical compositions having antiinflammatory and hypocholesterolemic activity comprise, as active ingredient, a 2-aminothiazole derivative of the first general formula above a mineral or organic acid addition or quaternary ammonium salt thereof, together with a physiologically acceptable carrier or excipient.