Heterocyclic substituted 2-acylamino-5-thiazoles, their preparation and pharmaceutical compositions containing them

2-Acylaminothiazole compound of the formula:

• ##STR110## in which R.sub.1 is hydrogen;
• R.sub.IV is (C.sub.3 -C.sub.7)cycloalkyl, (C.sub.1 -C.sub.4 )alkyl-substituted (C.sub.3 -C.sub.7)cycloalkyl, phenyl, or phenyl substituted by one or more halogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.3)alkoxy, (C.sub.1 -C.sub.3)thioalkoxy, nitro, or trifluoromethyl, or R.sub.IV and R.sub.V, taken together, are:
• ##STR111## in which u is an integer from 1 to 3, np is an integer from 0-3, Xp is halogen, (C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.3)alkoxy, nitro or trifluoromethyl, and Xp is the same or different when np is 2 or 3;
• R.sub.V is --(CH.sub.2).sub.m --X in which m is an integer from 0 to 5 and X is:
• (i) halogen, hydroxyl, (C.sub.3 -C.sub.7)cycloalkyl, phenyl, or phenyl substituted with halogen, (C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.3)alkoxy, nitro, amino, hydroxyl or trifluoromethyl;
• (ii) --COOH;
• --COOX.sub.1 ;
• --O--COX.sub.1 ;
• --SCOX.sub.1 ;
• ##STR112## wherein q is an integer from 0 to 2;
• ##STR113## wherein X.sub.3 is hydrogen or (C.sub.1 -C.sub.3)alkyl;
• ##STR114## wherein W is O or S;
• ##STR115## wherein s is an integer from 2 to 4;
• in which X.sub.1 is (C.sub.1 -C.sub.3)alkyl;
• phenyl;
• phenyl substituted by one or more halogen, (C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.3)alkoxy, nitro, amino, hydroxyl, or trifluoromethyl;
• or adamantyl;
• (iii) --NX.sub.1 X.sub.2 or --CONX.sub.1 X.sub.2 in which X.sub.1 is hydrogen, (C.sub.1 -C.sub.3)alkyl, phenyl, or phenyl substituted by one or more halogen, (C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.3)alkoxy, nitro, amino, hydroxy or trifluoromethyl, and X.sub.2 is hydrogen or (C.sub.1 -C.sub.3)alkyl;
• or alternatively, X.sub.1 and X.sub.2 constitute, with the nitrogen atom to which they are attached, pyrrolidino or pyrrolidino substituted by oxo, hydroxyl, --O--COR in which R is (C.sub.1 -C.sub.5)alkyl, (--OCOOX.sub.1), as defined above, or (--OCONX.sub.1 X.sub.2) as defined above;
• or alternatively,
• R.sub.V is (C.sub.1 -C.sub.5)alkoxy, hydroxyl, pyrrolidino, piperidino, pyrrolidino substituted by oxo or hydroxyl, piperidino substituted by oxo or hydroxyl, piperazinyl, or piperazinyl N-substituted by --COOAlk in which Alk is (C.sub.1 -C.sub.5)alkyl;
• a carboxylic acid group;
• --NX.sub.2 X.sub.4 in which X.sub.4 is hydrogen or --(CH.sub.2).sub.1 --X.sub.5 wherein t is an integer from 2 to 4 and X.sub.5 is --OH, --O--CO--R.sub.2, NHCOR.sub.2, or ##STR116## in which R.sub.2 is (C.sub.1 -C.sub.6)alkyl;
• or --NR.sub.2 R.sub.3 wherein R.sub.2 and R.sub.3 are independently H, (C.sub.1 -C.sub.6)alkyl, phenyl, phenyl substituted by one or more halogen, (C.sub.1 -C.sub.3)alkyl, or (C.sub.1 -C.sub.3)alkoxy, or R.sub.2 and R.sub.3 constitute, with the nitrogen atom to which they are attached, pyrrolidino, piperidino, pyrrolidino substituted by oxo or hydroxyl, piperidino substituted by oxo or hydroxyl, piperazinyl, or piperazinyl N-substituted by --COOAlk in which Alk is (C.sub.1 -C.sub.5)alkyl;
• and
• Z is indolyl, indolyl substituted by one or more halogen, (C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.3)alkoxy, benzyloxy, nitro, amino or trifluoromethyl, indoyl N-substituted by (C.sub.1 -C.sub.4)alkyl, or carboxyalkylene-Z.sub.4 --COOR.sub.10 in which Z.sub.4 is (C.sub.1 -C.sub.4)alkylene and R.sub.10 is hydrogen, benzyl, or (C.sub.1 -C.sub.6)alkyl, or indolyl substituted by one or more halogen, (C.sub.1 -C.sub.3)alkyl, (C.sub.1 -C.sub.3)alkoxy, benzyloxy, nitro, amino, or trifluoromethyl and N-substituted by (C.sub.1 -C.sub.4)alkyl or carboxyalkylene-Z.sub.4 --COOR.sub.10 is which Z.sub.4 is (C.sub.1 -C.sub.4)alkylene and R.sub.10 is hydrogen, benzyl, or (C.sub.1 -C.sub.6)alkyl;
• or a pharmaceutically acceptable salt thereof.