Heterocyclic substituted acylaminothiazoles, their preparation and pharmaceutical compositions containing them

Abstract

Compounds of formulain which R1 represents H, an alkyl or a substituted alkyl, R2 represents H or alkyl and R3 represents an optionally substituted cycloalkyl or an optionally substituted aromatic group, which can be a phenyl or a heterocyclic group comprising one or more hetero-atoms chosen from O, S and N, or R2 and R3 considered together represent the groupwhich is optionally substituted on the phenyl ring, and Z represents a heterocycle comprising one or more heteroatoms chosen from O, S and N, fused with an aromatic ring which can comprise a hetero-atom and can be substituted, the said heterocycle being optionally substituted on N, when it comprises such an atom, by an alkyl or a substituted alkyl group, and the salts of these compounds with acids or bases.Use of these compounds as medicaments.<DEL-S DATE="20010313" ID="DEL-S-00001">No figure.<DEL-E ID="DEL-S-00001">

We claim:  
     
       1. A 2-Acylaminothiazole of formula                    
       in which R 1  represents H, (C 1  to C 4 ) alkyl or phenyl(C 1 -C 3 )alkyl; aminoalkyl —Z 1 -NR 4 R 5 , in which Z 1  represents a (C 2  to C 4 ) alkylene and R 4  and R 5  independently represent H or (C 1  to C 4 ) alkyl, or form with N a saturated heterocycle and represent morpholino, pyrrolidinyl, piperidino, piperazinyl or 4-(C 1 -C 3 )alkylpiperazinyl; carboxyalkyl —Z 2 —COOR 6 , in which Z 2  represents (C 1  to C 4 ) alkylene and R 6  represents H or (C 1  to C 6 ) alkyl; (C 2  to C 5 ) cyanoalkyl; carbamoylalkyl —Z 3 —CONR 7 R 8 , in which Z 3  represents (C 1  to C 4 ) alkylene and R 7  and R 8  independently represent H or (C 1  to C 4 ) alkyl or, with N, represent a heterocycle selected from NR 4 R 5 ; (C 2  to C 6 ) hydroxyalkyl and (C 2  to C 10 ) alkoxyalkyl; 
       R 2  represents H or (C 1  to C 4 ) alkyl;  
       R 3  represents (C 5  to C 8 ) cycloalkyl, optionally substituted by one or more (C 1  to C 4 ) alkyl; an aromatic group, selected from phenyl, optionally carrying one or more substituents chosen from halogen, (C 1 -C 6 ) alkyl, (C 1 -C 3 ) alkoxy and (C 1 -C 3 ) thioalkoxy, nitro, trifluoromethyl and a heterocycle comprising at least one heteroatom chosen from O, S and N, and R 3  then represents furyl, thienyl, pyrroly  pyrrolyl, pyrazolyl, imidazolyl, pyridyl, pyrazinyl, oxazolyl or thiazolyl, optionally substituted by (C 1  to C 3 ) alkyl or halogen, or R 2  and R 3  considered together represent the group                    
       fixed by the carbon of the phenyl in position 4 of the thiazolyl and in which q is 1 to 4, and X p  represents the optional substituents chosen from halogen, (C 1 -C 3 ) alkyl, (C 1 -C 3 ) alkoxy, nitro and trifluoromethyl and np represents 0 to 3, and Z represents a heterocycle comprising one or more hetero-atoms chosen from O,  S and N, fused with an aromatic ring which may comprise a hetero-atom and which aromatic ring may be substituted by one or more groups chosen from halogen, (C 1 -C 3 ) alkyl, (C 1 -C 3 ) alkoxy, benzyloxy, nitro, amino and trifluoromethyl, and which heterocycle is unsubstituted or substituted on the N atom by C 1 -C 4  alkyl; C 1 -C 6  hydroxyalkyl; optionally cyclised (C 2 -C 10 ) alkoxyalkyl, aminoalkyl —Z 4 —NR 10 R 11  in which Z 4  represents (C 2 -C 4 ) alkylene and R 10  and R 11  independently represent H or (C 1 -C 4 ) alkyl, or NR 10 R 11  represents with N a saturated heterocyclic group selected from morpholino, pyrrolidinyl, piperidino, piperazinyl or 4-(C 1 -C 3 )-alkylpiperazinyl; carboxyalkyl —Z 5 —COOR 12  in which Z 5  represents (C 1 -C 4 ) alkylene and R 12  is H, benzyl or (C 1 -C 6 ) alkyl; carbamoylalkyl —Z 6 -CONR 13 R 14 , in which Z 6  represents (C 1 -C 4 ) alkylene and R 13  and R 14  independently represent H or (C 1 -C 6 ) alkyl or form, with N, a saturated heterocycle selected from NR 10 R 11 ; acyl —COR 15 , where R 15  represents (C 1 -C 4 ) alkyl or phenyl; or alkoxycarbonyl —COOR 16 , with R 16  being tert-butyl or benzyl; as well as the addition salts of the compounds of formula I with inorganic or organic acids and bases. 
     
     
       2. A Compound according to claim  1 , of formula I in which Z represents benzothienyl, benzofuranyl, benzoxazolyl,  benzimidazolyl, benzothiazolyl, quinolyl, isoquinolyl, quinoxalinyl, quinazolinyl, cinnolinyl and [2,3-c] or [3,2-c]thienopyridyl, isoindolyl, isoindolinyl, optionally substituted indolyl or indolinyl and the indolyl and indolinyl groups being optionally substituted on nitrogen. 
     
     
       3. A Compound according to claim  1 , of formula I, in which R 2  represents H, R 1  represents H, (C 1 -C 4 ) alkyl or —Z 1 —NR 4 R 5 , with Z 1 , R 4  and R 5  having the same meanings as in claim  1 , R 3  represents an at least ortho-substituted phenyl and Z represents an indolyl group which is unsubstituted or substituted on the nitrogen by (C 1 -C 4 ) alkyl, (C 2 -C 6 ) hydroxyalkyl; (C 2 -C 10 ) alkoxyalkyl; aminoalkyl —Z 4 —NR 10 —R 11  in which Z 4  represents (C 2 -C 4 ) alkylene and R 10  and R 11  independently represent H or (C 1 -C 4 ) alkyl, or NR 10 R 11  represents with N a saturated heterocyclic group selected from morpholino, pyrrolidinyl, piperidino, piperzinyl or 4-(C 1 -C 3 ) alkylpiperazinyl; carboxyalkyl —Z 5 —COOR 12  in which Z 5  represents (C 1 -C 4 ) alkylene and R 12  is H, benzyl or (C 1 -C 6 ) alkyl; carbamoylalkyl —Z 6 —CONR 13 R 14 , in which Z 6  represents (C 1 -C 4 ) alkylene and R 13  and R 14  independently represent H or (C 1 -C 6 ) alkyl or form, with N, a saturated heterocycle selected from NR 10 R 11 ; acyl —COR 15 , where R 15  represents (C 1 -C 4 ) alkyl or phenyl; or alkoxycarbonyl —COOR 16 , with R 16  being tert-butyl or benzyl; and their salts. 
     
     
       4. N-[4(2,4,6-Trimethylphenyl)-2-thiazolyl]-indole-2-carboxamide and its derivatives substituted on the indole nitrogen by Ch 3 , CH 2 COOH, CH 2 COOCH 3  or (CH 2 ) 2 N(CH 3 ) 2 , and their pharmaceutically acceptable salts. 
     
     
       5. N-[4(2,4,6-Trimethoxyphenyl)-2-thiazolyl]indole-   2    -N- [ 4   (   2 , 6   - Trimethoxyphenyl )-   2   - thiazolyl]indole -2-carboxamide and its derivatives substituted on the indole nitrogen by CH 3 ,k  CH 2 COOH, CH 2 COOCH 3  or (CH 2 ) 2 N(CH 3 ) 2 , and their pharmaceutically acceptable salts. 
     
     
       6. N-[4(2,4,6-Dimethylphenyl)-2-thiazolyl]-indole-   2   -  N- [ 4   (   2 , 6   - Dimethylphenyl )-   2   - thiazolyl] - indole -   2   -carboxamide and its derivatives substituted on the indole nitrogen by CH 2 COOH and CH 2 COOCH 3 , and their pharmaceutically acceptable salts. 
     
     
       7. N-[4-(2,4,6  2,6-Dimethoxyphenyl)-2-thiazolyl]-indole-2-carboxamide and its derivatives substituted on the indole nitrogen by CH 2 COOH and CH 2 COOH and CH 2 COOCH 3 , and their pharmaceutically acceptable salts. 
     
     
       8. N-[4(2,4,6-Dichlorophenyl)-2-thiazolyl]-indole-2- N- [ 4   (   2 , 6   - Dichlorophenyl )-   2   - thiazolyl] - indole -   2   -carboxamide and its derivatives substituted on the nitrogen by CH 2 COOH and (CH 2 ) 2 N(CH 3 ) 2 , and their pharmaceutically acceptable salts. 
     
     
       9. N-[4-(2-Methylphenyl)-2-thiazolyl]-indole-2-carboxamide, N-[4-(2-methoxyphenyl)-2-thiazolyl]-indole-2-carboxamide, N-[4-(2-chlorophenyl)-2-thiazolyl]-indole-2-carboxamide and their derivatives substituted on the nitrogen by CH 2 COOH and also their pharamaceutically acceptable salts. 
     
     
       10. N-[4-(4-Methylphenyl)-2-thiazolyl]-indole-2-carboxamide and N-[4-(4-methoxyphenyl)-2-thiazolyl]indole-2-carboxamide and their pharmaceutically acceptable salts. 
     
     
       11. N-[4-(2,4,6-trimethoxyphenyl)-2-thiazolyl]benzofuran-2-carboxamide and its pharmaceutically acceptable salts. 
     
     
       12. A 2-acylaminothiazole of formula                    
       in which 
       R 1  represents H, (C 1 -C 4 ) alkyl or phenyl(C 1 -C 3 )alkyl;  
       R 2  represents H or (C 1 -C 4 )alkyl;  
       R 3  represents (C 5 -C 8 )cycloalkyl, optionally substituted by one or more (C 1 -C 3 ) alkyl; an aromatic group optionally carrying one or more substituents chosen from halogen, (C 1 -C 3 )alkyl, (C 1 -C 3 ) alkoxy and (C 1 -C 3 )thioalkoxy, nitro, trifluoromethyl, said aromatic group being selected from phenyl and a heterocyclic group furyl, thienyl, pyrrolyl and pyridyl, or R 2  and R 3  considered together represent the group                    
       fixed by the carbon of the phenyl in position 4 of the thiazolyl and in which X 1  and X 2  each represents hydrogen, halogen, (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, nitro or trifluoromethyl, and q is 1 to 4, and Z represents a nitrogen comprising heterocycle fused with a phenyl ring selected from indolinyl, isoindolinyl, indolyl, isoindolyl, quinolyl and isoquinolyl, optionally substituted on the phenyl ring by one or more groups selected from halogen, (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy and thioalkoxy or the addition salt of this compound with a pharmaceutically acceptable acid. 
     
     
       13. A compound according to claim  12  of formula I in which Z represents a group selected from optionally substituted indolyl and quinolyl. 
     
     
       14. A 2-acylaminothiazole of formula                    
       in which 
       R 1  represents H, (C 1 -C 4 )alkyl or phenyl(C 1 -C 3 )alkyl; aminoalkyl —Z 1 —NR 4 R 5 , in which Z 1  represents a (C 2 -C 4 )alkylene and R 4  and R 5  independently represent H or (C 1 -C 4 )alkyl, or form with N a saturated heterocycle morpholino, pyrrolidinyl, piperidino, piperazinyl or 4-(C 1 -C 3 )alkylpiperazinyl; carboxyalkyl —Z 2 —COOR 6 , in which Z 2  represents (C 1 -C 4 )alkylene and R 6  represents H or (C 1 -C 6 )-alkyl; (C 2 -C 5 )cyanoalkyl; carbamoylalkyl —Z 3 -CONR 7 R 8 , in which Z 3  represents (C 1 -C 4 )alkylene and R 7  and R 8  independently represent H or (C 1 -C 4 )alkyl; (C 2 -C 6 )hydroxyalkyl or (C 2 -C 10 )alkoxyalkyl; R 2  represents H or (C 1  to C 4 )alkyl; R 3  represents (C 5 -C 8 )cycloalkyl, optionally substituted by one or more (C 1 -C 3 )alkyl; and  an aromatic group, optionally carrying one or more substituents selected from halogen, (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy and (C 1 -C 3 )thioalkoxy, nitro and trifluoromethyl, said aromatic group being selected from phenyl furyl, thienyl, pyrrolyl and pyridyl, or R 2  and R 3  considered together represent the group                    
       fixed by the carbon of the phenyl in position 4 of the thiazolyl and in which X 1  and X 2  each represents hydrogen, halogen, (C 1 -C 3 -alkyl, (C 1 -C 3 )alkoxy, nitro or trifluoromethyl, and q is 1 to 4, and 
       Z represents an indolyl group of formula                    
       in which R 9  represents (C 2 -C 6 )hydroxyalkyl; acyclic or cyclic (C 2 -C 10 )alkoxyalkyl; aminoalkyl —Z 4 —NR 10 R 11  in which Z 4  represents (C 2 -C 4 )alkylene and R 10  and R 11  independently represent H or (C 1 -C 4 )alkyl, or represent with N a saturated heterocyclic group selected from morpholino, pyrrolidinyl, piperidino, piperazinyl and 4-(C 1 -C 3 )alkylpiperazinyl; carboxyalkyl —Z 5 —COOR 12  in which Z 5  represents (C 1 -C 4 )alkylene and R 12  is H or (C 1 -C 6 )alkyl; cyano(C 1 -C 4 )alkyl; carbamoylalkyl Z 6 -CONR 13 R 14 , in which Z 6  represents (C 1 -C 4 )alkylene and R 13  and R 14  independently represent H or (C 1 -C 4 )alkyl or form, with N, a saturated heterocycle; acyl —COR 15 , where R 15  represents (C 1 -C 4 )alkyl or phenyl; or alkoxycarbonyl —COOR 16 , with R 16  being tert-butyl or benzyl; and in which the phenyl ring may be substituted with one or more groups selected from (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, halogen, trifluoromethyl, and nitro, or the pharmaceutically acceptable acid addition salt of this compound.  
     
     
       15. A pharmaceutical composition for the prevention or treatment of disorders requiring cholecystokinin or gastrin antagonists, characterized in that it comprises a pharmaceutically effective amount of at least one compound according to claim  1 , in combination with at least one excipient. 
     
     
       16. A pharmaceutical composition for the prevention or treatment of disorders requiring cholecystokinin or gastrin antagonists characterized in that it comprises a pharmaceutically effective amount of at least one compound according to claim  9  in combination with at least one excipient. 
     
     
       17. A pharmaceutical composition for the prevention or treatment of disorders requiring cholecystokinin or gastrin antagonists characterized in that it comprises a pharmaceutically effective amount of at least one compound according to claim  14  in combination with at least one excipient. 
     
     
       18. A pharmaceutical composition for the prevention or treatment of disorders requiring cholecystokinin or gastrin antagonists characterized in that it comprises a pharmaceutically effective amount of at least one  2 - acylaminothiazole of formula                      
       
         in which  
       
         R   1    represents H,  ( C   1    to C   4 )  alkyl or phenyl ( C   1   -C   3 ) alkyl; aminoalkyl —Z   1   —NR   4   R   5   , in which Z   1    represents a  ( C   2    to C   4 )  alkylene and R   4    and R   5    independently represent H or  ( C   1    to C   4 )  alkyl, or form with N a saturated heterocycle and represent morpholino, pyrrolidinyl, piperidino, piperazinyl or  4   -( C   1   -C   3 ) alkylpiperazinyl; carboxyalkyl —Z   2   —COOR   6   , in which Z   2    represents  ( C   1    to C   4 )  alkylene and R   6    represents H or  ( C   1    to C   6 )  alkyl;  ( C   2    to C   5 )  cyanoalkyl; carbamoylalkyl —Z   3   —CONR   7   R   8   , in which Z   3    represents  ( C   1    to C   4 )  alkylene and R   7    and R   8    independently represent H or  ( C   1    to C   4 )  alkyl or, with N, represent a heterocycle selected from NR   4   R   5 ; ( C   2    to C   6 )  hydroxyalkyl and  ( C   2    to C   10 )  alkoxyalkyl;    
         R   2    represents H or  ( C   1    to C   4 )  alkyl;    
         R   3    represents  ( C   5    to C   8 )  cycloalkyl, optionally substituted by one or more  ( C   1    to C   4 )  alkyl; an aromatic group, selected from phenyl, optionally carrying one or more substituents chosen from halogen,  ( C   1   -C   6 )  alkyl,  ( C   1   -C   3 )  alkoxy and  ( C   1   -C   3 )  thioalkoxy, nitro, trifluoromethyl and a heterocycle comprising at least one hetero - atom chosen from O, S and N, and R   3    then represents furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridyl, pyrazinyl, oxazolyl or thiazolyl, optionally substituted by  ( C   1    to C   3 )  alkyl or halogen, or R   2    and R   3    considered together represent the group                      
         fixed by the carbon of the phenyl in position  4  of the thiazolyl and in which q is  1  to  4 , and X   p    represents the optional substituents chosen from halogen,  ( C   1   -C   3 )  alkyl,  ( C   1   -C   3 )  alkoxy, nitro and trifluoromethyl and np represents  0  to  3 , and    
         Z represents a heterocycle comprising one or more hetero - atoms chosen from O, S and N, fused with an aromatic ring which may comprise a hetero - atom and which aromatic ring may be substituted by one or more groups chosen from halogen,  ( C   1   -C   3 )  alkyl,  ( C   1   -C   3 )  alkoxy, benzyloxy, nitro, amino and trifluoromethyl, and which heterocycle is unsubstituted or substituted on the N atom by C   1   -C   4    alkyl; C   1   -C   6    hydroxyalkyl; optionally cyclised  ( C   2   -C   10 )  alkoxyalkyl, aminoalkyl —Z   4   —NR   10   R   11    in which Z   4    represents  ( C   2   -C   4 )  alkylene and R   10    and R   11    independently represent H or  ( C   1   -C   4 )  alkyl, or NR   10   R   11    represents with N a saturated heterocyclic group selected from morpholino, pyrrolidinyl, piperidino, piperazinyl or  4   -( C   1   -C   3 )- alkylpiperazinyl; carboxyalkyl —Z   5   —COOR   12    in which Z   5    represents  ( C   1   -C   4 )  alkylene and R   12    is H, benzyl or  ( C   1   -C   6 )  alkyl; carbamoylalkyl —Z   6   —CONR   13   R   14   , in which Z   6    represents  ( C   1   -C   4 )  alkylene and R   13    and R   14    independently represent H or  ( C   1   -C   6 )  alkyl or form, with N, a saturated heterocycle selected from NR   10   R   11   ; acyl —COR   15   , where R   15    represents  ( C   1   -C   4 )  alkyl or phenyl; or alkoxycarbonyl —COOR   16   , with R   16    being tert - butyl or benzyl; as well as the addition salts of the compounds of formula I with inorganic or organic acids and bases, in combination with at least one excipient.   
     
     
       19. The pharmaceutical composition of claim  18  wherein Z represents benzothienyl, benzofuranyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, quinolyl, cinnolinyl and [ 2 , 3 - c] or [ 3 , 2   - c] thienopyridyl, isoindolyl, isoindolinyl, optionally substituted indolyl or indolinyl and the indolyl and indolinyl groups being optionally substituted on nitrogen.   
     
     
       20. A pharmaceutical composition for the prevention or treatment of disorders requiring cholecystokinin or gastrin antagonists characterized in that it comprises a pharmaceutically effective amount of at least one of N- [ 4   -(   2 , 4 , 6   - trimethoxy - phenyl )-   2   - thiazolyl] - benzofuran -   2   - carboxamide or a pharmaceutically acceptable salt thereof, in combination with at least one excipient.   
     
     
       21.  1 - Carboxymethyl - N - [ 4   -(   2   - chloromethyl )-   2   - thiazolyl]indole -   2   - carboxamide and its pharmaceutically acceptable salts.   
     
     
       22. A pharmaceutical composition for the prevention or treatment of disorders requiring cholecystokinin or gastrin antagonists characterized in that it comprises a pharmaceutically effective amount of at least one compound according to claim  21  in combination with at least one excipient. 
     
     
       23. A  2 - acylaminothiazole of formula                      
       
         in which  
       
         R   1    represents H,  ( C   1    to C   4 )  alkyl or phenyl  ( C   1   -C   3 )  alkyl; aminoalkyl—Z   1   —NR   4   R   5   , in which Z   1    represents a  ( C   2    to C   4 )  alkylene and R   4    and R   5    independently represent H or  ( C   1    to C   4 )  alkyl, or form with N a saturated heterocycle and represent morpholino, pyrrolidinyl, piperidino, piperazinyl or  4   -( C   1   -C   3 )  alkyl piperazinyl; carboxyalkyl—Z   2   —COOR   6   , in which Z   2    represents  ( C   1    to C   4 )  alkylene and R   6    represents H or  ( C   1    to C   6 )  alkyl;  ( C   2    to C   5 )  cyanoalkyl; carbamoylalkyl—Z   3   —CONR   7   R   8   , in which Z   3    represents  ( C   1    to C   4 )  alkylene and R   7    and R   8    independently represent H or  ( C   1    to C   4 )  alkyl or, with N, represent a heterocycle selected from NR   4   R   5 , ( C   2    to C   6 )  hydroxyalkyl and  ( C   2    to C   10 )  alkoxyalyl;    
         R   2    represents H or  ( C   1    to C   4 )  alkyl;    
         R   3    is selected from an aromatic heterocycle selected from the group consisting of furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyrazinyl, oxazolyl and thiazolyl, said aromatic heterocycle being optionally substituted by  ( C   1   -C   3 )  alkyl or halogen;  ( C   5   -C   8 )  cycloalkyl, optionally substituted by one or more  ( C   1   -C   4 )  alkyl;  2 , 6   - dimethyl -   4   - pyridyl; phenyl;  2   - methylphenyl;  2   - chlorophenyl;  2   - trifluoromethylphenyl;  4   - methylphenyl;  4   - methoxyphenyl;  4   - chlorophenyl;  2   - methoxyphenyl;  2 , 4   - dimethylphenyl;  2 , 6   - dimethylphenyl;  2 , 6   - dichlorophenyl;  3 , 4   - dichlorophenyl;  4   - cyclohexlphenyl,  2 , 4 , 6   - trimethylphenyl;  2 , 4 , 6   - triethylphenyl,  2 , 4 , 6   - triisopropylphenyl;  2 , 4 , 6   - trimethoxyphenyl;  2 , 4 , 6   - triethoxyphenyl;  3 , 4 , 5   - trimethoxyphenyl;  2   - hydroxy -   4 , 6   - dimethoxyphenyl;  2 , 6   - dimethoxy -   4   - hydroxyphenyl;  2 , 4   - dimethyl -   6   - methoxyphenyl; and  2 , 6   - dimethyl -   4   - acetylaminophenyl or R   2    and R   3    considered together represent the group                      
         fixed by the carbon of the phenyl in position  4  of the thiazolyl and in which q is  1  to  4 , and X   p    represents the optional substituents chosen from halogen,  ( C   1   -C   3    alkyl ), ( C   1   -C   3 )  alkoxy, nitro and trifluoromethyl and np represents  0  to  3 , and Z represents a heterocycle comprising one or more hetero - atoms chosen from S and N, fused with an aromatic ring which may comprise a hetero - atom and which aromatic ring may be substituted by one or more groups chosen from halogen,  ( C   1   -C   3 )  alkyl,  ( C   1   -C   3 )  alkoxy, benzyloxy, nitro, amino and trifluoromethyl and which heterocycle is unsubstituted or substituted on the N atom by C   1   -C   4    alkyl, C   1   -C   6    hydroxyalkyl; optionally cyclised  ( C   2   -C   10 )  alkoxyalkyl, aminoalkyl —Z   4   —NR   10   R   11    in which Z   4    represents  ( C   2   -C   4 )  alkylene and R   10    and R   11    independently represent H or  ( C   1   -C   4 )  alkyl, or NR   10   R   11    represents with N a saturated heterocyclic group selected from morpholino, pyrrolidinyl, piperidino, piperazinyl or  4   -( C   1   -C   3 )- alkylpiperazinyl; carboxyalkyl —Z   5   —COOR   12    in which Z   5    represents  ( C   1   -C   4 )  alkylene and R   12    is H, benzyl or  ( C   1   -C   6 )  alkyl; carbamoylalkyl —Z   6   —CONR   13   R   14   , in which Z   6    represents  ( C   1   -C   4 )  alkylene and R   13    and R   14    independently represent H or  ( C   1   -C   6 )  alkyl or form, with N, a saturated heterocycle selected from NR   10   R   11   ; acyl - COR   15   , where R   15    represents  ( C   1   -C   4 )  alkyl or phenyl; or alkoxycarbonyl - COOR   16   , with R   16    being tert - butyl or benzyl; as well as the addition salts of the compounds of formula I with inorganic or organic acids and bases.   
     
     
       24. A  2 - acylaminothiazole of formula                      
       
         in which  
       
         R   1    represents H,  ( C   1    to C   4 )  alkyl or phenyl ( C   1   -C   3 ) alkyl; aminoalkyl —Z   1   —NR   4   R   5   , in which Z   1    represents a  ( C   2    to C   4 )  alkylene and R   4    and R   5    independently represent H or  ( C   1    to C   4 )  alkyl, or form with N a saturated heterocycle and represent morpholino, pyrrolidinyl, piperidino, piperazinyl or  4   -( C   1   -C   3 ) alkylpiperazinyl; carboxyalkyl —Z   2   —COOR   6   , in which Z   2    represents  ( C   1    to C   4 )  alkylene and R   6    represents H or  ( C   1    to C   6 )  alkyl;  ( C   2    to C   5 )  cyanoalkyl; carbamoylalkyl —Z   3   —CONR   7   R   8   , in which Z   3    represents  ( C   1    to C   4 )  alkylene and R   7    and R   8    independently represent H or  ( C   1    to C   4 )  alkyl or, with N, represent a heterocycle selected from NR   4   R   5 ; ( C   2    to C   6 )  hydroxyalkyl and  ( C   2    to C   10 )  alkoxyalkyl;    
         R   2    represents H or  ( C   1    to C   4 )  alkyl;    
         R   3    represents  ( C   5    to C   8 )  cycloalkyl, optionally substituted by one or more  ( C   1    to C   4 )  alkyl; an aromatic group, selected from phenyl, optionally carrying one or more substituents chosen from halogen,  ( C   1   -C   6 )  alkyl,  ( C   1   -C   3 )  alkoxy and  ( C   1   -C   3 )  thioalkoxy, nitro, trifluoromethyl and a heterocycle comprising at least one hetero - atom chosen from O, S and N, and R   3    then represents furyl, thienyl, pyrrolyl, pyrazolyl, imidazolyl, pyridyl, pyrazinyl, oxazolyl or thiazolyl, optionally substituted by  ( C   1    to C   3 )  alkyl or halogen, or R   2    and R   3    considered together represent the group                      
         fixed by the carbon of the phenyl in position  4  of the thiazolyl and in which q is  1  to  4 , and X   p    represents the optional substituents chosen from halogen,  ( C   1   -C   3 )  alkyl,  ( C   1   -C   3 )  alkoxy, nitro and trifluoromethyl and np represents  0  to  3 , and    
         Z represents a heterocycle comprising one or more hetero - atoms chosen from O, S and N, fused with an aromatic ring which may comprise a hetero - atom and which aromatic ring may be substituted by one or more groups chosen from halogen,  ( C   1   -C   3 )  alkyl,  ( C   1   -C   3 )  alkoxy, benzyloxy, nitro, amino and trifluoromethyl, and which heterocycle is unsubstituted or substituted on the N atom by C   1   -C   4    alkyl; C   1   -C   6    hydroxyalkyl; optionally cyclised  ( C   2   -C   10 )  alkoxyalkyl, aminoalkyl —Z   4   —NR   10   R   11    in which Z   4    represents  ( C   2   -C   4 )  alkylene and R   10    and R   11    independently represent H or  ( C   1   -C   4 )  alkyl, or NR   10   R   11    represents with N a saturated heterocyclic group selected from morpholino, pyrrolidinyl, piperidino, piperazinyl or  4   -( C   1   -C   3 )- alkylpiperazinyl; carboxyalkyl —Z   5   —COOR   12    in which Z   5    represents  ( C   1   -C   4 )  alkylene and R   12    is H, benzyl or  ( C   1   -C   6 )  alkyl; carbamoylalkyl —Z   6   —CONR   13   R   14   , in which Z   6    represents  ( C   1   -C   4 )  alkylene and R   13    and R   14    independently represent H or  ( C   1   -C   6 )  alkyl or form, with N, a saturated heterocycle selected from NR   10   R   11   ; acyl —COR   15   , where R   15    represents  ( C   1   -C   4 )  alkyl or phenyl; or alkoxycarbonyl —COOR   16   , with R   16    being tert - butyl or benzyl;    
         with the proviso that when R   1    and R   2    are both hydrogen and R   3    represents phenyl optionally substituted by one or more groups selected from chlorine, bromine, methoxy, ethoxy, propoxy and isopropoxy then Z does not represent  2   - benzofuranyl or  2   -(   2 , 3   - dihydrobenzuranyl;    
       
         as well as the addition salts of the compounds of formula I with inorganic or organic acids and bases, in combination with at least one excipient. 
       
     
     
       25. A compound according to claim  24  of formula I in which Z represents benzothienyl, benzofuranyl, benzoxazolyl, benzimidazolyl, benzothiazolyl, quinolyl, isoquinolyl, quinoxalinyl, quinazolinyl, cinnolinyl and [ 2 , 3 - c] or [ 3 , 2   - c] thienopyridyl, isoindolyl, isoindolinyl, optionally substituted indolyl or indolinyl and the indolyl and indolinyl groups being optionally substituted on nitrogen.   
     
     
       26. A pharmaceutical composition for the prevention or treatment of disorders requiring cholecystokinin or gastrin antagonists characterized in that it comprises a pharmaceutically effective amount of at least one compound according to claim  24  in combination with at least one excipient.