Erythromycin derivatives, method for preparing same, and use thereof as drugs

Abstract

A subject of the invention is the compounds of formula (I): in which: X represents a CH 2 or SO 2 radical or an oxygen atom, Y represents a (CH 2 ) m —(CH═CH) n (CH 2 ) o radical, with m+n+o≦8, n=0 or 1, Ar represents an aryl radical, W represents a hydrogen atom, or the remainder of a carbamate function. The compounds of formula (I) have useful antibiotic properties.

We claim:  
     
       1. A compound selected from the group consisting of ( a )                    
       wherein X is selected from the group consisting of —CH 2 —, —SO 2 —SO 2   —  and —O—, Y is —(CH 2 ) m —(CH═CH n )—CH 2 ) o —  —( CH   2 ) m —( CH═CH ) n —( CH   2 ) o   — , m+N+n+o≦8, n is 0 or 1, Ar is aryl or  heterocycle aryl, the aryl and  heterocycle aryl being unsubstituted or substituted with at least one substituent selected from the group consisting of —OH, halogen, —NO 2 , —CN, alkyl, alkenyl and alkynyl of up to 12 carbon atoms, optionally substituted with at least one halogen, alkoxy, alkenyloxy and alkynyloxy of up to  12  carbon atoms optionally substituted with at least one halogen, alkylthio, alkenylthio and alkynylthio of up to 12 carbon atoms optionally substituted with at least one halogen, N-alkyl, N-alkenyl and N-alkynyl of up to 12 carbon atoms optionally substituted with at least one halogen,                    
       R a  and R b  are individually hydrogen or alkyl of 1 to 12 carbon atoms, R 3  is selected from the group consisting of 1 to 12 carbon atoms, aryl and heteroaryl, W is hydrogen or                    
       R″ is alkyl of 1 to 8 carbon atoms or Ar is unsubstituted or substituted aryl, the substituents being at least one member of the group consisting of —OH, halogen, —NO 2 , —CN, alkyl, alkenyl or alkynyl, O-alkyl, O-alkenyl, O-alkynyl, S-alkyl, S-alkenyl, S-alkynyl, N-alkyl, N-alkenyl and N-alkynyl containing up to 12 carbon atoms optionally substituted by at least one halogen, Z is hydrogen or acyl of an organic carboxylic acid and non-toxic, pharmaceutically acceptable acid addition salts of the compound of Formula I; and ( b )    11 , 12   - dideoxy -   3   - de ((   2 , 6   - dideoxy -   3   - C - methyl -   3   - O - methyl - alpha - L - ribohexopyranosyl ) oxy )-   3   - hydroxy -   6   - O - methyl -   12 , 11   -( oxycarbonyl (   2   -(   3   -(   4   - quinolinyl ) propyl ) hydrazono ))- erythromycin.    
     
     
       2. A compound of  claim 1  selected from the group consisting of -11,12-dideoxy-3-de((2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyl)oxy)-3-hydroxy-6-O-methyl-12,11-(oxycarbonyl((4-(4-(3-pyridinyl)-1H-imidazol-1-yl)-butyl)imino))-erythromycin and -11,12-dideoxy-3-de((2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyl)oxy)-3-hydroxy-6-O-methyl-12,11-(oxycarbonyl(2-(3-(4-quinolinyl)propyl)hydrazono))erythromycin. 
     
     
       3. Pharmaceutical compositions containing at least one medicament according to  claim 1  as active ingredient. 
     
     
       4. A process for the preparation of a compound of  claim 1  comprising reacting a compound of the formula                    
       wherein X, Y and Ar are defined in  claim 1  with an acid to obtain a compound of the formula                    
       wherein X, Y and Ar are defined as above and optionally reacting the latter with an esterification agent or with an agent capable of introducing the carbamate radical. 
     
     
       5. A method of treating bacterial infections in a warm-blooded animal comprising administering to a warm-blooded animal a bactericidally effective amount of a compound of  claim 1 . 
     
     
       6. The method of  claim 5  wherein the compound is selected from the group consisting of -11,12-dideoxy-3-de((2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyl) oxy)-3-hydroxy-6-O-methyl-12,11-(oxycarbonyl((4-(4-(3-pyridinyl)-1H-imidazol-1-yl)-butyl)imino))-erythromycin and -11,12-dideoxy-3-de((2,6-dideoxy-3-C-methyl-3-O-methyl-alpha-L-ribohexopyranosyl)oxy)-3-hydroxy-6-O-methyl-12,11-(oxycarbonyl(2-(3-(4-quinolinyl)propyl)hydrazono))-erythromycin. 
     
     
       7. A compound of  claim 1  wherein Z is hydrogen. 
     
     
       8. A compound of  claim 1  wherein w is hydrogen. 
     
     
       9. A compound of  claim 1  wherein X is —CH 2 . 
     
     
       10. A compound of  claim 1  wherein Y is —(CH 2 ) n  and n is 2 or 4 or 5  —( CH   2 ) 3 —, —( CH   2 ) 4 —,  or — ( CH   2 ) 5 —. 
     
     
       11. A compound of  claim 1  wherein Rr is heterocyclic aryl. 
     
     
       12. A compound of claim  11   1 wherein Ar is 4-quinolinyl mono or polysubstituted. 
     
     
       13. A compound of claim  11   1 wherein Ar is unsubstituted 4-quinolinyl. 
     
     
       14. A compound of  claim 1  wherein Ar is optionally substituted                    
     
     
       15. A bactericidally effective amount of a compound  claim 1  and an inert pharmaceutical carrier.