Erythromycin compounds

Claim 2

A compound of the formula ##STR27## wherein R is ##STR28## or --(CH 2 ) 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 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 1 and R 2 are individually hydrogen or alkyl of up to 12 carbon atoms, ##STR31## R 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.

Claim 3

A compound of claim 1 wherein Z is hydrogen.

Claim 4

A compound of claim 1 wherein Z is 4.

Claim 5

A compound of claim 1 wherein Ar is ##STR32## optionally substituted.

Claim 6

A compound of claim 1 wherein Ar is ##STR33## optionally substituted.

Claim 7

A compound of claim 1 wherein Ar is selected from the group consisting of ##STR34## optionally substituted.

Claim 8

A compound of claim 1 wherein Ar is ##STR35## optionally substituted.

Claim 9

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-α-L-ribohexopyranosyl)-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-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(3H-imidazo(4,5-b)pyridin-3-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(1H-imidazo(4,5-b)pyridin-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(4-chlorophenyl)-1H-imidazol-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-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-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(4-fluorophenyl)-1H-imidazol-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(7-methoxy-4-quinoleinyl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(2-(2-pyridinyl)-4-thiazolyl)-butyl)-imino)]-erythromycin,

Claim 10

12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-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.

Claim 11

12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-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.

Claim 12

A compound of claim 1 which is 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(3-pyridinyl)-1H-imidazol-1-yl)-butyl)-imino)]-erythromycin.

Claim 13

An antibacterial composition comprising an antibiotically effective amount of a compound of claim 1 and an inert pharmaceutical carrier.

Claim 14

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.

Claim 15

A method of claim 11 wherein Z is hydrogen.

Claim 16

A method of claim 11 wherein n is 4.

Claim 17

A method of claim 11 wherein Ar is ##STR36## optionally substituted.

Claim 18

A method of claim 11 wherein Ar is ##STR37## optionally substituted.

Claim 19

A method of claim 11 wherein Ar is selected from the group consisting of ##STR38## optionally substituted.

Claim 20

A method of claim 11 wherein Ar is ##STR39## optionally substituted.

Claim 21

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-α-L-ribohexopyranosyl)-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-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(3H-imidazo(4,5-b)pyridin-3-yl)-butyl)-imino)]-erythromycin,

Claim 22

12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(1H-imidazo(4,5-b)pyridin-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(4-chlorophenyl)-1H-imidazol-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-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-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(4-fluorophenyl)-1H-imidazol-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(7-methoxy-4-quinoleinyl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(2-(2-pyridinyl)-4-thiazolyl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-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.

Claim 23

12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(1H-imidazo(4,5-b)pyridin-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(4-chlorophenyl)-1H-imidazol-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-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-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(4-fluorophenyl)-1H-imidazol-1-yl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(7-methoxy-4-quinoleinyl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(2-(2-pyridinyl)-4-thiazolyl)-butyl)-imino)]-erythromycin, 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-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.

Claim 24

A method of claim 11 wherein the compound is 11,12-dideoxy-3-de-[(2,6-dideoxy-3-C-methyl-3-O-methyl-α-L-ribohexopyranosyl)-oxy)-6-O-methyl-3-oxo-12,11-(oxycarbonyl-((4-(4-(3-pyridinyl)-1H-imidazol-1-yl)-butyl)-imino)]-erythromycin.