Claims for Patent: 5,635,485

Summary for Patent: 5,635,485

Title:	Erythromycin compounds
Abstract:	An erythromycin compound of Formula I or its non-toxic acid addition salt having antibiotic activity.
Inventor(s):	Agouridas; Constantin (Nogent sur Maine, FR), Chantot; Jean-Francois (Nogent sur Maine, FR), Denis; Alexis (Paris, FR), D'Ambrieres; Solange G. (Paris, FR), Martret; Odile L. (Paris, FR)
Assignee:	Roussel Uclaf (FR)
Application Number:	08/426,067
Patent Claims:	1. A compound of the formula ##STR27## wherein R is ##STR28## or --(CH.sub.2).sub.n --Ar, n is an integer from 3 to 5, Ar is an optionally substituted heterocyclic selected from the group consisting of ##STR29## the optional substituents are at least one member selected from the group consisting of a free, salified, esterified and amidified carboxyl, hydroxyl, halogen, --NO.sub.2, --CN, alkyl, cycloalkyl, alkenyl, alkynyl, O-alkyl, O-alkenyl, O-alkynyl, S-alkyl, S-alkenyl, S-alkynyl, N-alkyl, N-alkenyl and N-alkynyl of up to 12 carbon atoms optionally substituted by one or more halogens, ##STR30## R.sub.1 and R.sub.2 are individually hydrogen or alkyl of up to 12 carbon atoms, ##STR31## R.sub.3 is alkyl of up to 12 carbon atoms, and d) an optionally substituted carbocyclic O-aryl and S-aryl and heterocyclic aryl, O-aryl and S-aryl and Z is hydrogen or an acid remainder or its non-toxic, pharmaceutically acceptable acid addition salts. 2. A compound of claim 1 wherein Z is hydrogen. 3. A compound of claim 1 wherein Z is 4. 4. A compound of claim 1 wherein Ar is ##STR32## optionally substituted. 5. A compound of claim 1 wherein Ar is ##STR33## optionally substituted. 6. A compound of claim 1 wherein Ar is selected from the group consisting of ##STR34## optionally substituted. 7. A compound of claim 1 wherein Ar is ##STR35## optionally substituted. 8. 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-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-phenyl-1H-imidazol -1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(3H-imidazo(4,5-b)pyr idin-3-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(1H-imidazo(4,5-b)pyr idin-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(4-chlorophenyl)-1 H-imidazol-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(2-methoxyphenyl)- 1H-imidazol-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(4-fluorophenyl)-1 H-imidazol-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(7-methoxy-4-quinolei nyl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(2-(2-pyridinyl)-4-th iazolyl)-butyl)-imino)]-erythromycin, 11. 12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexop yranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(3-(3-pyridinyl)-1H- 1,2,4-triazol-1-yl)-butyl)-imino)]-erythromycin, and their non-toxic, pharmaceutically acceptable acid addition salts. 9. A compound of claim 1 which is 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexop yranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(3-pyridinyl)-1H- imidazol-1-yl)-butyl)-imino)]-erythromycin. 10. An antibacterial composition comprising an antibiotically effective amount of a compound of claim 1 and an inert pharmaceutical carrier. 11. A method of treating bacterial infections in warm-blooded animals comprising administering to warm-blooded animals having a bacterial infection an antibiotically effective amount of a compound of claim 1. 12. A method of claim 11 wherein Z is hydrogen. 13. A method of claim 11 wherein n is 4. 14. A method of claim 11 wherein Ar is ##STR36## optionally substituted. 15. A method of claim 11 wherein Ar is ##STR37## optionally substituted. 16. A method of claim 11 wherein Ar is selected from the group consisting of ##STR38## optionally substituted. 17. A method of claim 11 wherein Ar is ##STR39## optionally substituted. 18. A method of claim 11 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-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-phenyl-1H-imidazol -1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(3H-imidazo(4,5-b)pyr idin-3-yl)-butyl)-imino)]-erythromycin, 11. 12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexop yranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(1H-imidazo(4,5-b)py ridin-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(4-chlorophenyl)-1 H-imidazol-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(2-methoxyphenyl)- 1H-imidazol-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(4-fluorophenyl)-1 H-imidazol-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(7-methoxy-4-quinolei nyl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(2-(2-pyridinyl)-4-th iazolyl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopy ranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(3-(3-pyridinyl)-1H-1 ,2,4-triazol-1-yl)-butyl)-imino)]-erythromycin, and their non-toxic, pharmaceutically acceptable acid addition salts. 19. A method of claim 11 wherein the compound is 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexop yranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(3-pyridinyl)-1H- imidazol-1-yl)-butyl)-imino)]-erythromycin.