9-OXIME ERYTHROMYCIN DERIVATIVES Background Of The Invention This invention relates to novel 3-keto-9-oxime-11,12-carbazate or carbamate derivatives of 6-O-methyl-erythromycin A. The compounds of this invention are useful as antibiotic agents in mammals, including man, as well as in fish and birds. The compounds of the present invention are broad-spectrum macrolide antibiotics that are effective against infections caused by certain gram-positive and gram-negative bacteria as well as protozoa.

Summary of the Invention The present invention relates to compounds of the formula and to pharmaceutically acceptable salts thereof, wherein: X is -CR7R8-or-NR7-; or X is taken together with R2 to form -N=CR4R5; or X and R2 are taken together to form a heterocyclic ring of the formula XVI: wherein in said ring of formula XVI, r and p are each independently an integer ranging from 1 to 3, q is 0 or 1, and X1 is -CH2-, O, S, -C(O)-, -C(S)-, -SO2-, -CH=CH-, -CH(OH)CH(OH)- or -NH-; and wherein the (CH2)r and (CH2)p portions of said ring of formula XVI are optionally

substituted by 1 to 4 substituents, and the nitrogen atom where X' is -NH- is optionally substituted by 1 substituent, said optional substituents being independently selected from the group consisting of -C(O)O(C1-C10 alkyl), C,-C,0 alkoxy, C1-C10 alkanoyl, halo, nitro, cyano, 5-10 membered heterocyclyl, C1-C10 alkyl, -NR7R8, C6-C10 aryl, ~S(O)n(C1-C10 alkyl) wherein n is an integer ranging from 0 to 2, and -SO2NR7R8; R1 is H or C1-C10 alkyl, wherein 1 to 3 carbons of said alkyl are optionally replaced by a heteroatom selected from 0, S and N, and said alkyl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of -C(O)O(C1-C10 alkyl), C,-C10 alkoxy, C1-C10 alkanoyl, halo, nitro, cyano, 5-10 membered heterocyclyl, C1-C10 alkyl, -NR7R8, <BR> <BR> <BR> CgC10 0 aryl, -S(O)n(C1-C10 alkyl) wherein n is an integer ranging from 0 to 2, and -So2NR7R8; <BR> <BR> <BR> <BR> R2 is (i) H, R4,-C(O)R4, -C(O)OR4 or on -(CR7R8)mR3 when X is -NR7-, or (ii) H, R4, or -(CR7R8)mR3 when X is -CR7R8-, wherein for both (i) and (ii) m is an integer ranging from 0 to 6 and both R7 and R8 may vary for each iteration where mis greater than 1; each R is independently C6-C10 0 aryl or 5-10 membered heterocyclyl, wherein said aryl and heterocyclyl groups are optionally substituted by 1 to 3 substituents independently selected from the group consisting of -C(O)O(C1-C10 alkyl), C1-C10 alkoxy, C1-C10 alkanoyl, halo, nitro, cyano, 5-10 membered heterocyclyl, C6-C10 aryl, C1-C10 alkyl, -NR7R8, -S(O)n(C1-C10 alkyi) wherein n is an integer ranging from 0 to 2, and -SO2NR7R8; and, each R4 and R5 is independently selected from H and C1-C12 alkyl wherein one or two carbons of said alkyl are optionally replaced by a heteroatom selected from 0, S and N, and wherein said alkyl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of -C(O)O(C1-C10 alkyl), C1-C10 alkoxy, C1-C10 alkanoyl, halo, nitro, cyano, C1- C10 alkyl, -NR7R8, C6-C10 aryl, 5-10 membered heterocyclyl, -S(O)n(C1-C10 alkyl) wherein n is an integer ranging from 0 to 2, and -SO2NR7R8; R6 is H, -C(O)R3 or Ci-Cia alkanoyl, wherein in the alkyl portion of said alkanoyl one or two carbons optionally may be replaced by a heteroatom selected from 0, S and N; and, each R7 and R8 is independently H or C,-C6 alkyl.

More specific embodiments of this invention include compounds of formula I wherein R6 is H.

Other more specific embodiments of this invention include compounds of formula I wherein X is -NH-.

Other more specific embodiments of this invention include compounds of formula I wherein R is H, benzyl or C1-C3 alkyl or -CH2O(CH2)2OCH3.

Other more specific embodiments of this invention include compounds of formula I wherein R2 is -(CH2)mR3 wherein m is an integer ranging from 0 to 6 and R3 is 5-10 membered

heterocyclyl or C6-C10 aryl. Specific embodiments of R3 include quinolin-4-yl, 4-phenyl-imidazol- 1 -yl, imidazo(4,5-b)pyridin-3-yl, 4-pyridin-3-ylimidazol-1 -yl and pyridin-3-yl.

Examples of preferred compounds of this invention include: 9-Deoxo-1 1 -deoxy-5-Odesosaminyl-1 1 -(3-(4-pyridin-3-yl-imidazol-1 -yl)-propyl)hydrazo- 9-hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1-(3-(4-pyridin-3-yl-imidazol-1 -yl)-propyl)hydrazo- 9-methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-imidazo(4,5-b)pyridin -3-yl)-propyl)hydrazo- 9-hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1-deoxy-5-O-desosaminyl-1 1-(3-(imidazo(4,5-b)pyridin-3-yl)-propyl)hydrazo- 9-methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1-(3-quinolin-4-yl-propyl)hydrazo-9-hydroxyimino- 6-O-methyl-3-oxoerythronolide A, 11 ,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-yuinolin-4-yl-propyl) hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(7-methoxy-quinoliln- 4-yl)-propyl))hydrazo-9 hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(6-methoxy-quinolin-4 -yl)-propyl))hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-quinolin-4-yl-propyli dene)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-quinolin-4-yl-propyli dene)hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-quinolin-4-yl-propyl) hydrazo-9-benzoxyimino- 6-O-methyl-3-oxoerythronolide A, 11 ,12-carbamate; 19-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-benzoimidazol-1-yl-p ropyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 1 9-Deoxo-1 -deoxy-5-O-desosaminyl-1 1-(3-benzoimidazol-1 -yl-propyl)hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1-deoxy-5-O-desosaminyl-1 1-(3-indol-1-yl-propyl)hydrazo-9-hydroxyimino-6- O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-indol-1-yl-propyl)hyd razo-9-methoxyimino-6- O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1-(3-indazol-1 -yl-propyl)hydrazo-9-hydroxyimino- 6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-indazol-1-yl-propyl)h ydrazo-9-methoxyimino- 6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate;

9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1-(3-carbazol-1 -yl-propyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-carbazol-1-yl-propyl) hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1-(3-(5-phenyl-1 H-pyrrol-2-yl)-propyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1-deoxy-5-O-desosaminyl-1 1-(3-(5-phenyl-1 H-pyrrol-2-yl)-propyl)hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo- 11 -deoxy-5-O-desosaminyl- 11 -(3-(4-phenyl-imidazol- 1 -yl)-propyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(4-phenyl-imidazol-1- yl)- propyl)hydrazo-9-methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-(3-(4-chlorophenyl)-(1 ,2,4)oxadizol-5-yl)- propyl)hydrazo-9-hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-(3-(4-chlorophenyl)-(1 ,2,4)oxadizol-5-yl)- propyl)hydrazo-9-methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 19-Deoxo-1-deoxy-5-O-desosaminyl-11-(3-(3-(4-methoxyphenyl)- (1,2,4)oxadizol-5-yl)- propyl)hydrazo-9-hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 1 9-Deoxo-1 -deoxy-5-O-desosaminyl-1 1 -(3-(3-(4-methoxyphenyl)- (1 ,2,4)oxadizol-5-yl)- propyl)hydrazo-9-methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(3-(4-pyridin-4-yl)-( 1,2,4)oxadizol-5-yl)- propyl)hydrazo-9-hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1-deoxy-5-O-desosaminyl-1 1 -(3-(3-(4-pyridin-4-yl)-(1 ,2,4)oxadizol-5-yl)- propyl)hydrazo-9-methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1-deoxy-5-O-desosaminyl-1 1 -(3-naphthalen-1 -yl-propyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-naphthalen-1-yl-propy l)hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-benzotrizol-1-yl-prop yl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1-deoxy-5-O-desosaminyl-1 1 -(3-benzotrizol-1 -yl-propyl)hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-benzotrizol-2-yl-propyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-benzotrizol-2-yl-prop yl)hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate;

9-Deoxo-11-deoxy-5-O-deosaminyl-11-(3-(1H-indol-3-yl)-propyl )hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-deosaminyl-11-(3-(1H-indol-3-yl)-propyl )hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-deosaminyl-11-(3-pyridin-4-yl-propyl)hy drazo-9-hydroxyimino- 6-O-methyl-3-oxoerythronolide A, 11 ,12-carbamate; 9-Deoxo- 11 -deoxy-5-O-desosaminyl-1 1 -(3-pyridin-4-yl-propyl)hydrazo-9-methoxyimino- 6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-pyridin-3-yl-propyl)hydrazo-9-hydroxyimino- 6-O-methyl-3-oxoerythronolide A, 1 1 ,1 2-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-pyridin-3-yl-propyl)hydrazo-9-methoxyimino- 6-O-methyl-3-oxoerythronolide A, 11 ,12-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-(pyridin-2-yl-propyl)hydrazo-9-hydroxyimino- 6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-deosaminyl-11-(3-(pyridin-2-yl-propyl)h ydrazo-9-methoxyimino- 6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-phenylpropyl) hydrazo-9-hydroxyimino-6-O- methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-deosaminyl-11-(3-phenylpropyl)hydrazo-9 -methoxyimino-6-O- methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-deosaminyl-11-bis-(3-phenylpropyl)hydra zo-9-hydroxyimino-6- O-methyl-3-oxoerythronolide A, 11 ,12-carbamate; 9-Deoxo-11-deoxy-5-O-deosaminyl-11-bis-(3-phenylpropyl)hydra zo-9-methoxyimino-6- O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-deosaminyl-11-(3-(4-methoxyphenyl)-prop yl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11 ,12-carbamate; 9-Deoxo-11-deoxy-5-O-deosaminyl-11-(3-(4-methoxyphenyl)-prop yl)hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-deosaminyl-11-(3-(3-methoxyphenyl)-prop yl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo- 11 -deoxy-5-O-desosaminyl-1 1 -(3-(3-methoxyphenyl)-propyl)hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-deosaminyl-11-(3-(2-methoxyphenyl)-prop yl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-deosaminyl-11-(3-(2-methoxyphenyl)-prop yl)hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate;

9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(4-hydroxyphenyl)-pro pyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-(4-hydroxyphenyl)-propyl)hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 (3-(3-methoxyphenyl)-propyl)hydrazo-9 hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(3-methoxyphenyl)-pro pyl)hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(2-phenylehyl)hydrazo-9- hydroxyimino-6-O- methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(2-phenylehyl)hydrazo-9- methoxyimino-6-O- methyl-3-oxoerythronolide A, 1 11 2-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(4-phenylbutyl)hydrazo-9 -hydroxyimino-6-O methyl-3-oxoerythronolide A, 1 1,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(4-phenylbutyl)hydrazo-9 -methoxyimino-6-O- methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-furan-2-yl-propyl)hydrazo-9-hydroxyimino-6- O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-furan-2-yl-propyl)hydrazo-9-methoxyimino-6- O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-thiophen-2-yl-propyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-thiophen-2-yl-propyl)hydrazo-9-methoxyimino-6-O- methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-pyrrol-1-yl-propyl)hy drazo-9-hydroxyimino-6- O-methyl-3-oxoerythronolide A, 11 ,12-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-pyrrol-1 -yl-propyl)hydrazo-9-methoxyimino-6- O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-pyrazol-1-yl-propyl)h ydrazo-9-hydroxyimino- 6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-pyrazol-1-yl-propyl)h ydrazo-9-methoxyimino- 6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(2-pyridin-3-yl-thiaz ol-4-yl)-propyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(2-pyridin-3-yl-thiaz ol-4-yl)- propyl)hydrazo-9-methoxyimino-6-O-methyl-3-oxoeiythronolide A, 11,1 2-carbamate;

9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-(2-phenyl-thiazol-5-yl)-propyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11 ,12-carbamate; 9-Deoxo-1 1-deoxy-5-O-desosaminyl-1 1-(3-(2-phenyl-thiazol-5-yl)-propyl)hydrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1-deoxy-5-O-desosaminyl-1 1-(3-(4-phenyl-1 H-imidazol-2-yl)-propyl)hydrazo- 9-hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-(4-pheriyl-1 H-imidazol-2-yl)-propyl)hydrazo- 9-methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 0-epl-1 1 -hydrazo-9-benzoxyimino-6-O-methyl-3- oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 -deoxy-5-O-desosaminyl-1 0-epl-1 1 -hydrazo-9-hydroxyimino-6-O-methyl-3- oxoerythronolide A, 11 ,12-carbamate; and the pharmaceutically acceptable salts of the foregoing compounds.

The invention also relates to a pharmaceutical composition for the treatment of a bacterial infection or a protozoa infection in a mammal, fish, or bird which comprises a therapeutically effective amount of a compound of formula I, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

The invention also relates to a method of treating a bacterial infection or a protozoa infection in a mammal, fish, or bird which comprises administering to said mammal, fish or bird a therapeutically effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof.

The term "treatment", as used herein, unless otherwise indicated, includes the treatment or prevention of a bacterial infection or protozoa infection as provided in the method of the present invention.

As used herein, unless otherwise indicated, the term bacterial infection(s)" or protozoa infection" includes bacterial infections and protozoa infections that occur in mammals, fish and birds as well as disorders related to bacterial infections and protozoa infections that may be treated or prevented by administering antibiotics such as the compounds of the present invention. Such bacterial infections and protozoa infections and disorders related to such infections include the following: pneumonia, otitis media, sinusitus, bronchitis, tonsillitis, and mastoiditis related to infection by Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus, or Peptostreptococcus spp.; pharynigitis, rheumatic fever, and glomerulonephritis related to infection by Streptococcus pyogenes, Groups C and G streptococci, Clostridium diptheriae, or Actinobacillus haemolyticum; respiratory tract infections related to infection by Mycoplasma pneumoniae, Legionella pneumophila, Streptococcus pneumoniae, Haemophilus influenzae, or Chlamydia pneumoniae; uncomplicated skin and soft tissue infections, abscesses and osteomyelitis, and puerperal fever related to

infection by Staphylococcus aureus, coagulase-positive staphylococci (i.e., S. epidermidis, S. hemolyticus, etc.), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcal groups C- F (minute-colony streptococci), viridans streptococci, Corynebacterium minutissimum, Clostridium spp., or Bartonella henselae; uncomplicated acute urinary tract infections related to infection by Staphylococcus saprophyticus or Enterococcus spp.; urethritis and cervicitis; and sexually transmitted diseases related to infection by Chlamydia trachomatis, Haemophilus ducreyi, Treponema pallidum, Urea plasma urealyticum, or Neiserria gonorrheae; toxin diseases related to infection by S. aureus (food poisoning and Toxic shock syndrome), or Groups A, B, and C streptococci; ulcers related to infection by Helicobacter pylori; systemic febrile syndromes related to infection by Borrelia recurrentis; Lyme disease related to infection by Borrelia burgdorferi; conjunctivitis, keratitis, and dacrocystitis related to infection by Chlamydia trachomafis, Neisseria gonorhoeae, S. aureus, S. pneumoniae, S. pyogenes, H. influenzae, or Listeria spp.; disseminated Mycobacterium avium complex (MAC) disease related to infection by Mycobacterium avium, or Mycobacterium intracellulare; gastroenteritis related to infection by Campylobacter jejuni; intestinal protozoa related to infection by Cryptosporidium spp.; odontogenic infection related to infection by viridans streptococci; persistent cough related to infection by Bordetella pertussis; gas gangrene related to infection by Clostridium perfringens or Bacteroides spp.; and atherosclerosis related to infection by Helicobacter pylori or Chlamydia pneumoniae. Bacterial infections and protozoa infections and disorders related to such infections that may be treated or prevented in animals include the following: bovine respiratory disease related to infection by P. haem., P. multocida, Mycoplasma bovis, or Bordetella spp.; cow enteric disease related to infection by E. coli or protozoa (i.e., coccidia, cryptosporidia, etc.); dairy cow mastitis related to infection by Staph. aureus, Strep. uberis, Strep. agalactiae, Strep. dysgalactiae, Klebsiella spp., Corynebacterium, or Enterococcus spp.; swine respiratory disease related to infection by A. pleuro., P. multocida, or Mycoplasma spp.; swine enteric disease related to infection by E. coli, Lawsonia intracellulads, Salmonella, or Serpulina hyodyisinteriae; cow footrot related to infection by Fusobacterium spp.; cow metritis related to infection by E; coil; cow hairy warts related to infection by Fusobacterium necrophorum or Bacteroides nodosus; cow pink-eye related to infection by Moraxella bovis; cow premature abortion related to infection by protozoa (i.e. neosporium); urinary tract infection in dogs and cats related to infection by E. coli; skin and soft tissue infections in dogs and cats related to infection by Staph. epidermidis, Staph. intermedius, coagulase neg. Staph. or P. multocida; and dental or mouth infections in dogs and cats related to infection by Alcaligenes spp., Bacteroides spp., Clostridium spp., Enterobacter spp., Eubacterium, Peptostreptococcus, Porphyromonas, or Prevofella.

Other bacterial infections and protozoa infections and disorders related to such infections that may be treated or prevented in accord with the method of the present invention are referred to in J. P. Sanford et al., "The Sanford Guide To Antimicrobial Therapy," 26th Edition, (Antimicrobial Therapy, Inc., 1996).

The invention also relates to a process of preparing the compound of formula 1, and pharmaceutically acceptable salts thereof, wherein R', R2, R6 and X are as defined above, which comprises treating a compound of the formula wherein X and R2 are as defined above, with a compound of the formula RtONH2 HCI or R1ONH2,wherein R1 is as defined for said compound of formula I, in the presence of an acid, in a polar solvent such as methanol, ethanol, or isopropyl alcohol. Preferably, said acid is PyHCi, wherein Py denotes pyridine, or EtN"HCl.

In the chemical structures depicted herein, a wavy line indicates that the stereochemistry at the chiral center to which the wavy line is connected is either an R or S configuration where the wavy line is connected to a carbon atom. In the compound of formula I, the wavy line at position 10 of the macrolide ring indicates that the methyl group can be either R or S configuration at that position. In the compound of formula I, the wavy line connected to the oxime nitrogen at position 9 of the macrolide ring indicates that the -OR1 moiety is in an E or Z configuration.

The term "halo", as used herein, unless otherwise indicated, means fluoro, chloro, bromo or iodo. Preferred halo groups are fluoro, chloro and bromo.

The term "alkyl", as used herein, unless otherwise indicated, includes saturated monovalent hydrocarbon radicals having straight, cyclic or branched moieties, or mixtures thereof. Said alkyl group may include one or two double or triple bonds. It is understood that for cyclic moieties at least three carbon atoms are required in said alkyl group.

The term "alkanoyl", as used herein, unless otherwise indicated, includes -C(O)-alkyl groups wherein "alkyl" is as defined above.

The term "aryl", as used herein, unless otherwise indicated, includes an organic radical derived from an aromatic hydrocarbon by removal of one hydrogen, such as phenyl or naphthyl.

The term "5-10 membered heterocyclyl", as used herein, unless otherwise indicated, includes aromatic and non-aromatic heterocyclic groups containing one or more heteroatoms each selected from 0, S and N, wherein each heterocyclic group has from 5-10 atoms in its ring system. The heterocyclic groups include benzo-fused ring systems and ring systems substituted with one or more oxo moieties. An example of a 5 membered heterocyclic group is thiazolyl, and an example of a 10 membered heterocyclic group is quinolinyl. Examples of non-aromatic heterocyclic groups are pyrrolidinyl, piperidino, morpholino, thiomorpholino and piperazinyl.

Examples of aromatic heterocyciic groups are pyridinyl, imidazolyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl and thiazolyl. Heterocyclic groups having a fused benzene ring include benzimidazolyl.

The phrase "pharmaceutically acceptable salt(s)", as used herein, unless otherwise indicated, includes salts of acidic or basic groups which may be present in the compounds of formula I. The compounds of formula I that are basic in nature are capable of forming a wide variety of salts with various inorganic and organic acids. The acids that may be used to prepare pharmaceutically acceptable acid addition salts of such basic compounds of formula I are those that form non-toxic acid addition salts, i.e., salts containing pharmacologically acceptable anions, such as the hydrochloride, hydrobromide, hydroiodide, nitrate, sulfate, bisulfate, phosphate, acid phosphate, isonicotinate, acetate, lactate, salicylate, citrate, acid citrate, tartrate, pantothenate, bitartrate, ascorbate, succinate, maleate, gentisinate, fumarate, gluconate, glucaronate, saccharate, formate, benzoate, glutamate, methanesulfonate, ethanesulfonate, benzenesulfonate, p-toluenesulfonate and pamoate [we., 1,1'-methylene-bis-(2- hydroxy-3-naphthoate)] salts.

Those compounds of the formula I that are acidic in nature, are capable of forming base salts with various pharmacologically acceptable cations. Examples of such salts include the alkali metal or alkaline earth metal salts and particularly, the sodium and potassium salts.

The present invention also includes all radiolabelled forms of the compounds of formula I, and pharmaceutically acceptable salts thereof, wherein the radiolabel is selected from 3H, 11C and 14C. Such radiolabelled compounds are useful as research or diagnostic tools.

Certain compounds of formula I may have asymmetric centers and therefore exist in different enantiomeric forms. This invention relates to the use of all optical isomers and stereoisomers of the compounds of formula I and mixtures thereof. In particular, the invention includes both the R and S configurations of the methyl group at C-10 of the macrolide ring of formula I, and both the E and Z configurations of the -OR1 group connected to the nitrogen of the oxime moiety at C-9 of the macrolide ring of formula I. The compounds of formula I may also exist as tautomers. This invention relates to the use of all such tautomers and mixtures thereof.

Detailed Descriotion of the Invention The preparation of the compounds of the present invention is illustrated in the following Schemes.

Scheme 1 Scheme 2 Scheme 2 continued Scheme 2 continued Scheme 3

In the above Schemes, Ac" indicates an acetyl group. The compounds of the present invention are readily prepared. Scheme 1 illustrates the general synthesis of the compounds of the present invention. In Scheme 1, the starting compound of formula II can be prepared as described in United States patent 5,543,400 (issued August 6, 1996). In general, the intermediate compound of formula Ill can be prepared as described in United States patent 5,543,400, referred to above, United States patent 5,527,780 (issued June 18, 1996), United Kingdom patent application number 2,288,174 (published October 11, 1995), and G.

Griesgraber ef aL, "3-Keto-11,12-carbazate Derivatives of 6-O-Methylerythromycin A," Journal of Antibiotics, 49(5), 465-477 (1996).

In step 1 of Scheme 1, compounds of the formula Ill, wherein X is -CR7R~- and R2 is as defined above, can be prepared by treating a compound of the formula Il with a compound of the formula H2N-X-R2, wherein X and R2 are as indicated for said compound of formula Ill, in a solvent such as acetonitrile, dimethyiformamide (DMF), tetrahydrofuran (THF), dimethoxy ethane or dimethylsulfoxide (DMSO), at a temperature within the range of about 500C to 90"C for a period of about 4 to 10 hours. The preparation of compounds of the formula Ill wherein X is -CR7R8- is described in further detail in United States patents 5,543,400 and 5,527,780, referred to above. Compounds of the formula Ill, wherein X is -NH- and R2 is as defined above, can be prepared by treating a compound of the formula II with a compound of the formula H2NNHR2, wherein R2 is as defined above, in a solvent such as acetonitrile, dioxane, or DMSO, at a temperature within the range of about 40"C to 90"C for a period of about 12 hours. The preparation of the compound of formula Ill wherein X is -NH- is described in further'detail in United Kingdom patent application number 2,288,174, referred to above. In step 2 of Scheme 1, compounds of the formula I can be prepared by treating a compound of the formula Ill with a compound of the formula RONH2*HCI or RONH2, wherein R1 is as defined above, in the presence of an acid, such as Py HCI, wherein Py denotes pyridine, or EtN"HCI, in a polar solvent, preferably methanol, ethanol, or isopropyi alcohol, at a temperature within the range of about 650C to 950C for a period of about 10 hours to 6 days.

Scheme 2 illustrates an altemative method of preparing compounds of the formula I wherein X is -NH-. In Scheme 2, the compound of formula IV can be prepared according to the procedures described in Baker et al., Journal of Organic Chemistry, 53, 2340 (1988). In step 1 of Scheme 2, the compound of formula V can be prepared by treating the compound of formula IV with hydrazine according to the procedure described above for the preparation of the compound of formula Ill wherein X is -NH-. Preferably, the compound of formula V is prepared by treating a compound of formula IV with anhydrous hydrazine in a solvent such as MeCN or DMF at a temperature of from about 600C to 900C for about 12 hours. In step 2 of Scheme 2, the compound of formula VI can be prepared by treating a compound of formula V with an acid, such as hydrochloric acid, in a solvent such as methanol or ethanol. In step 3 of Scheme 2, the

compound of formula VII can be prepared by treating a compound of formula VI with a compound of the formula R3-(CH2)rn.1-C(O)H, wherein m is 1 to 7 and R3 is as defined above, in an anhydrous solvent, such as anhydrous ethanol or isopropanol, at a temperature within the range of about 80"C to 90"C.

In steps 4 and 5 of Scheme 2, the hydroxy group at position C-2' of the compound of formula VII is protected as an acetate by treating the compound with acetic anhydride to form the compound of formula VIII, followed by oxidation of the hydroxy group at position 3 to provide a carbonyl group. Preferably, this is done by treating the compound of formula VII with acetic anhydride in a solvent such as CH2C12 at ambient temperature to provide the compound of formula Veil. The compound of formula IX can be prepared by treating a compound of formula VEIL, in a solvent such as CH2C12, with DMSO, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDAC) and pyridinium trifluoroacetate (PyTFA) at ambient temperature. The compound of formula X can be prepared by treating the compound of formula IX with a reducing agent such as NaBH3CN in a solvent such as methanol at ambient temperature. The compound of formula Xl can be prepared as described above for step 2 of Scheme 1.

Scheme 3 illustrates an additional method of preparing compounds of the formula I wherein X is -NH-. In Scheme 3, the compound of formula XII can be prepared according to the procedures described in Griesgraber et al., Joumal of Antibiotics, 49(5), 465-477 (1966). In step 1 of Scheme 3, the compound of formula Xll can be prepared by treating the compound of formula XII with a compound of the formula R1ONH2"HCl or R'ONH2 in the presence of an acid such as Py HCI, wherein Py denotes pyridine, or Et3N"HCl, in a polar solvent, preferably ethanol, methanol, or isopropyl alcohol, at a temperature within the range of about 65"C to 950C for a period of about 10 hours to 4 days. In step 2 of Scheme 3, the compound of formula XIII can be converted to the compound of formula XIV according to the procedure of step 3 of Scheme 2. In step 3 of Scheme 3, the compound of formula XIV can be converted to the compound of formula XV according to the procedure of step 6 of Scheme 2.

The compounds of the present invention may have asymmetric carbon atoms. Such diasteromeric mixtures can be separated into their individual diastereomers on the basis of their physical chemical differences by methods known to those skilled in the art, for example, by chromatography or fractional crystallization. Enantiomers can be separated by converting the enantiomeric mixtures into a diastereomric mixture by reaction with an appropriate optically active compound (e.g., alcohol), separating the diastereomers and converting (e.g., hydrolyzing) the individual diastereomers to the corresponding pure enantiomers. All such isomers, including diastereomer mixtures and pure enantiomers are considered as part of the invention.

The compounds of formula I that are basic in nature are capable of forming a wide variety of different salts with various inorganic and organic acids. Although such salts must be pharmaceutically acceptable for administration to animals, it is often desirable in practice to

initially isolate the compound of formula I from the reaction mixture as a pharmaceutically unacceptable salt and then simply convert the latter back to the free base compound by treatment with an alkaline reagent and subsequently convert the latter free base to a pharmaceutically acceptable acid addition salt. The acid addition salts of the base compounds of this invention are readily prepared by treating the base compound with a substantially equivalent amount of the chosen mineral or organic acid in an aqueous solvent medium or in a suitable organic solvent, such as methanol or ethanol. Upon careful evaporation of the solvent, the desired solid salt is readily obtained. The desired acid salt can also be precipitated from a solution of the free base in an organic solvent by adding to the solution an appropriate mineral or organic acid.

Those compounds of the formula I that are acidic in nature, are capable of forming base salts with various pharmacologically acceptable cations. Examples of such salts include the alkali metal or alkaline-earth metal salts and particularly, the sodium and potassium salts.

These salts may be prepared by conventional techniques. The chemical bases which are used as reagents to prepare the pharmaceutically acceptable base salts of this invention are those which form non-toxic base salts with the acidic compounds of formula I. Such non-toxic base salts include those derived from such pharmacologically acceptable cations as sodium, potassium calcium and magnesium, etc. These salts can be prepared by treating the corresponding acidic compounds with an aqueous solution containing the desired pharmacologically acceptable cations, and then evaporating the resulting solution to dryness, preferably under reduced pressure. Altematively, they may also be prepared by mixing lower alkanolic solutions of the acidic compounds and the desired alkali metal alkoxide together, and then evaporating the resulting solution to dryness in the same manner as before. In either case, stoichiometric quantities of reagents are preferably employed in order to ensure completeness of reaction and maximum yields of the desired final product.

The activity of the compounds of the present invention against bacterial and protozoa pathogens is demonstrated by the compound's ability to inhibit growth of defined strains of human (Assay I) or animal (Assays II and Ill) pathogens.

Assav I Assay I, described below, employs conventional methodology and interpretation criteria and is designed to provide direction for chemical modifications that may lead to compounds that circumvent defined mechanisms of macrolide resistance. In Assay I, a panel of bacterial strains is assembled to include a variety of target pathogenic species, including representatives of macrolide resistance mechanisms that have been characterized. Use of this panel enables the chemical structurelactivity relationship to be determined with respect to potency, spectrum of activity, and structural elements or modifications that may be necessary to obviate resistance mechanisms. Bacterial pathogens that comprise the screening panel are shown in the table

below. In many cases, both the macrolide-susceptible parent strain and the macrolide-resistant strain derived from it are available to provide a more accurate assessment of the compound's ability to circumvent the resistance mechanism. Strains that contain the gene with the designation of ermA/ermB/ermC are resistant to macrolides, lincosamides, and streptogramin B antibiotics due to modifications (methylation) of 23S rRNA molecules by an Erm methylase, thereby generally prevent the binding of all three structural classes. Two types of macrolide efflux have been described; msrA encodes a component of an efflux system in staphylococci that prevents the entry of macrolides and streptogramins while mefAlE encodes a transmembrane protein that appears to efflux only macrolides. Inactivation of macrolide antibiotics can occur and can be mediated by either a phosphorylation of the 2'-hydroxyl (mph) or by cleavage of the macrocyclic lactone (esterase). The strains may be characterized using conventional polymerase chain reaction (PCR) technology and/or by sequencing the resistance determinant. The use of PCR technology in this application is described in J. Sutcliffe et al., "Detection Of Erythromycin-Resistant Determinants By PCR", Antimicrobial Agents and Chemotherapy, 40(11), 2562-2566 (1996). The assay is performed in microtiter trays and interpreted according to Performance Standards for Antimicrobial Disk Susceptibilitv Tests - Sixth Edition: ADDroved Standard, published by The National Committee for Clinical Laboratory Standards (NCCLS) guidelines; the minimum inhibitory concentration (MIC) is used to compare strains. Compounds are initially dissolved in dimethylsulfoxide (DMSO) as 40 mg/ml stock solutions. Strain Designation Macrolide Resistance Mechanism(s) Staphylococcus aureus 1116 susceptible parent Staphylococcus aureus 1117 errnB Staphylococcus aureus 0052 susceptible parent Staphylococcus aureus 1120 ennC Staphylococcus aureus 1032 msrA, mph, esterase Staphylococcus hemolyticus 1006 msrA, mph Streptococcus pyogenes 0203 susceptible parent Streptococcus pyogenes 1079 ermB Streptococcus pyogenes 1062 susceptible parent Streptococcus pyogenes 1061 ermB Streptococcus pyogenes 1064 ermB Streptococcus agalactiae 1024 susceptible parent Streptococcus agalactiae 1023 ermB Streptococcus pneumoniae 1016 susceptible

Streptococcus pneumoniae 1046 enmB Streptococcus pneumoniae 1095 ermB Streptococcus pneumoniae 1175 mefE Streptococcus pneumoniae 0085 susceptible Haemophilus influenzae 0131 susceptible Moraxella catarrhalis 0040 susceptible Moraxella catarrhalis 1055 erythromycin intermediate resistance Escherichia coli 0266 susceptible Assay II is utilized to test for activity against Pasteurella multocida and Assay Ill is utilized to test for activity against Pa ste urella haemolytica.

Assav II This assay is based on the liquid dilution method in microliter format. A single colony of P. multocida (strain 59A067) is inoculated into 5 ml of brain heart infusion (BHI) broth. The test compounds are prepared by solubilizing 1 mg of the compound in 125 cil of dimethylsulfoxide (DMSO). Dilutions of the test compound are prepared using uninoculated BHl broth. The concentrations of the test compound used range from 200 pg/ml to 0.098 llg/ml by two-fold serial dilutions. The P. multocida inoculated BHl is diluted with uninoculated BHl broth to make a 104 cell suspension per 200 curl. The BHl cell suspensions are mixed with respective serial dilutions of the test compound, and incubated at 37"C for 18 hours. The minimum inhibitory concentration (MIC) is equal to the concentration of the compound exhibiting 100% inhibition of growth of P. multocida as determined by comparison with an uninoculated control.

Assav Ill This assay is based on the agar dilution method using a Steers Replicator. Two to five colonies isolated from an agar plate are inoculated into BHI broth and incubated overnight at 37~C with shaking (200 rpm). The next moming, 300 pl of the fully grown P. haemolytica preculture is inoculated into 3 ml of fresh BHI broth and is incubated at 37~C with shaking (200 rpm). The appropriate amounts of the test compounds are dissolved in ethanol and a series of two-fold serial dilutions are prepared. Two ml of the respective serial dilution is mixed with 18 ml of molten BHI agar and solidified. When the inoculated P. haemolytica culture reaches 0.5 McFarland standard density, about 5 pl of the P. haemolytica culture is inoculated onto BHI agar plates containing the various concentrations of the test compound using a Steers Replicator and incubated for 18 hours at 370C. Initial concentrations of the test compound range from 100-200 pg/ml. The MIC is equal to the concentration of the test compound exhibiting 100% inhibition of growth of P. haemolytica as determined by comparison with an uninoculated control.

The in vivo activity of the compounds of formula (I) can be determined by conventional animal protection studies well known to those skilled in the art, usually canied out in mice.

Mice are allotted to cages (10 per cage) upon their arrival, and allowed to acclimate for a minimum of 48 hours before being used. Animals are inoculated with 0.5 ml of a 3 x 103 CFU/ml bacterial suspension (P. multocida strain 59A006) intraperitoneally. Each experiment has at least 3 non-medicated control groups including one infected with 0.1X challenge dose and two infected with 1X challenge dose; a lOX challenge data group may also be used. Generally, all mice in a given study can be challenged within 30-90 minutes, especially if a repeating syringe (such as a Cornwalls syringe) is used to administer the challenge. Thirty minutes after challenging has begun, the first compound treatment is given. It may be necessary for a second person to begin compound dosing if all of the animals have not been challenged at the end of 30 minutes. The routes of administration are subcutaneous or oral doses. Subcutaneous doses are administered into the loose skin in the back of the neck whereas oral doses are given by means of a feeding needle. In both cases, a volume of 0.2 ml is used per mouse. Compounds are administered 30 minutes, 4 hours, and 24 hours after challenge. A control compound of known efficacy administered by the same route is included in each test. Animals are observed daily, and the number of survivors in each group is recorded. The P. multocida model monitoring continues for 96 hours (four days) post challenge.

The PDso is a calculated dose at which the compound tested protects 50% of a group of mice from mortality due to the bacterial infection which would be lethal in the absence of drug treatment.

The compounds of formula I, and the pharmaceutically acceptable salts thereof (hereinafter "the active compounds"), may be adminstered through oral, parenteral, topical, or rectal routes in the treatment or prevention of bacterial or protozoa infections. In general, these compounds are most desirably administered in dosages ranging from about 0.2 mg per kg body weight per day (mg/kg/day) to about 200 mg/kg/day in single or divided doses (i.e., from 1 to 4 doses per day), although variations will necessarily occur depending upon the species, weight and condition of the subject being treated and the particular route of administration chosen.

However, a dosage level that is in the range of about 4 mg/kg/day to about 50 mg/kg/day is most desirably employed. Variations may nevertheless occur depending upon the species of mammal, fish or bird being treated and its individual response to said medicament, as well as on the type of pharmaceutical formulation chosen and the time period and interval at which such administration is canied out. In some instances, dosage levels below the lower limit of the aforesaid range may be more than adequate, while in other cases still larger doses may be employed without causing any harmful side effects, provided that such larger doses are first divided into several small doses for administration throughout the day.

The active compounds may be administered alone or in combination with pharmaceutically acceptable carriers or diluents by the routes previously indicated, and such administration may be canied out in single or multiple doses. More particularly, the active compounds may be administered in a wide variety of different dosage forms, i.e., they may be combined with various pharmaceutically acceptable inert carriers in the form of tablets, capsules, lozenges, troches, hard candies, powders, sprays, creams, salves, suppositories, jellies, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, elixirs, syrups, and the like. Such caniers include solid diluents or fillers, sterile aqueous media and various non-toxic organic solvents, etc. Moreover, oral pharmaceutical compositions can be suitably sweetened and/or flavored. In general, the active compounds are present in such dosage forms at concentration levels ranging from about 5.0% to about 70% by weight.

For oral administration, tablets containing various excipients such as microcrystalline cellulose, sodium citrate, calcium carbonate, dicalcium phosphate and glycine may be employed along with various disintegrants such as starch (and preferably corn, potato or tapioca starch), alginic acid and certain complex silicates, together with granulation binders like polyvinylpyrrolidone, sucrose, gelatin and acacia. Additionally, lubricating agents such as magnesium stearate, sodium lauryl sulfate and talc are often very useful for tabletting purposes.

Solid compositions of a similar type may also be employed as fillers in gelatin capsules; preferred materials in this connection also include lactose or milk sugar as well as high molecular weight polyethylene glycols. When aqueous suspensions and/or elixirs are desired for oral adinistration, the active compound may be combined with various sweetening or flavoring agents, coloring matter or dyes, and, if so desired, emulsifying and/or suspending agents as well, together with such diluents as water, ethanol, propylene glycol, glycerin and various like combinations thereof.

For parenteral administration, solutions of an active compound in either sesame or peanut oil or in aqueous propylene glycol may be employed. The aqueous solutions should be suitably buffered (preferably pH greater than 8) if necessary and the liquid diluent first rendered isotonic. These aqueous solutions are suitable for intravenous injection purposes. The oily solutions are suitable for intraarticular, intramuscular and subcutaneous injection purposes. The preparation of all these solutions under sterile conditions is readily accomplished by standard pharmaceutical techniques will known to those skilled in the art.

Additionally, it is also possible to administer the active compounds of the present invention topically and this may be done by way of creams, jellies, gels, pastes, patches, ointments and the like, in accordance with standard pharmaceutical practice.

For administration to animals other than humans, such as cattle or domestic animals, the active compounds may be administered in the feed of the animals or orally as a drench composition.

The active compounds may also be adminstered in the form of liposome delivery systems, such as small unilamellar vesicles, large unilamellar vesicles and multilamellar vesicles. Liposomes can be formed from a variety of phospholipids, such as cholesterol, stearylamine or phosphatidylcholines.

The active compounds may also be coupled with soluble polymers as targetable drug carriers. Such polymers can include polyvinylpyrrolidone, pyran copolymer, polyhydroxypropylmethacrylamide phenyl, polyhydroxyethylaspartamide-phenol, or polyethyleneoxide-polylysine substituted with palmitoylresidues. Furthermore, the active compounds may be coupled to a class of biodegradable polymers useful in achieving controlled release of a drug, for example, polylactic acid, polyglycolic acid, copolymers of polylactic and polyglycolic acid, polyepsilon caprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals, polydihydropyrans, polycyanoacrylates and cross-linked or amphipathic biock copolymers of hydrogels.

The Examples provided below illustrate specific embodiments of the invention, but the invention is not limited in scope to the Examples specificaliy exemplified.

Example 1 4"-Acetvl-1 1-deoxv-1 -hvdrazo-6-O-methvlervthromvcin A, 1 1 11 .12-carbamate To a solution of 10,11-anhydro-2',4'-di-O-acetyl-12-O-imidazolylcarbonyl-6-O- methylerythromycin A (460 mg, 0.51 mmol) (which was prepared following the procedures of Baker et al., J. Org. Chem., 1988, 53, 2340), in MeCN at room temperature was added anhydrous NH2NH2 (0.16 mL, 5.1 mmol) and the resulting solution was heated at 60~C for 12 hours. MeCN was removed in vacuo, brine and EtOAc were added, and the aqueous layer was extracted with EtOAc (3 times). The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude product was purified by silica gel flash chromatography (1.5% Et3N-I .5% MeOH-97% MeOBu-t) to afford the title compound as a white solid (261 mg, 62%) and 4"-acetyl-I 0-epi-I 1-deoxy-11-hydrazo-6-O-methylerythromycin A, 11,12-carbamate as a white solid (38 mg, 10%).

For the title compound: 1H NMR (400 MHz, CDCl3) 6: 5.02 (1H, dd, J = 1.6, 10.8 Hz), <BR> <BR> <BR> 4.94 (IH, d, J = 4.8 Hz), 4.65 (1H, d, J = 10.0 Hz), 4.53 (IH, d, J = 7.2 Hz), 4.33 (IH, m), 3.82- 3.30 (m), 3.29 (3H, s), 3.20-3.00 (m), 3.00 (3H, s), 2.92-2.31 (m), 2.27 (6H, s), 2.08 (3H, s), 2.0- 1.4 (m), and 0.82 (3H, t, J = 7.6 Hz); MS: m/z 830 (M+H).

For 4"-acetyl-10-epi-11-deoxy-11 -hydrazo-6-O-methylerythromycin A, 11,1 2-Carbamate: 6: 'H NMR (400 MHz, CDCl3): 5.05 (1H, d, J = 4.4 Hz), 4.87 (1H, dd, J = 1.6, 10.8 Hz), 4.64 (1H, d, J = 10.0 Hz), 4.43 (1H, d, J = 7.6 Hz), 4.33 (1H, m), 3.84-3.32 (m), 3.30 (3H, s), 3.18 (3H, s), 3.2-2.3 (m), 2.23 (6H, s), 2.08 (3H, s), 1.62 (3H, s), 1.30 (3H, s), 0.97 (3H, d, J = 6.8 Hz), and 0.84 (3H, t, J = 7.2 Hz); MS: m/z 830 (M+H).

Example 2 11 -Deoxv-5-O-desosaminvl-1 1 -hvdrazo-6-O-methvlervthronolide A. 11.1 2-carbamate A solution of 4"-acetyl-1 1-deoxy-1 1-hydrazo-6-O-methylerythromycin A, 11,12- carbamate (40 mg, 0.048 mmol) in EtOH-2N HCI (1 : 2) was stirred at room temperature ovemight and the reaction mixture was poured into a cold solution of saturated NaHCO3. The aqueous layer was extracted with CHCl3 (3 times). The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude product was purified by silica gel flash chromatography (5% MeOH-0.5% NH3*H2O-94.5% CH2C12) to afford the title compound as a white solid (26.1 mg, 86%): rH NMR (400 MHz, CDCI3) 8: 5.09 (1H, dd, J = 2.4, 10.8 Hz), 4.45 (1H, s), 4.38 (1H, d, J = 7.6 Hz), 3.9-3.0 (m), 2.95 (3H, s), 2.75-2.45 (m), 2.27 (6H, s), 2.0-1.4 (m), 1.40 (3H, s), 1.34 (3H, s), 1.24 (3H, d, J = 6.8 Hz), 1.23 (3H, d, J = 6.0 Hz), 1.12 (3H, d, J = 7.2 Hz), 1.09 (3H, d, J = 7.2 Hz), 1.07 (3H, d, J = 6.8 Hz), and 0.80 (3H, t, J = 7.6 Hz).

13C NMR (100.6 MHz, CDCI3) 8: 216.90, 175.69, 156.45, 106.65, 88.29, 81.46, 78.74, 78.36, 75.78, 70.63, 70.23, 65.71, 63.37, 49.30, 45.35, 44.66, 40.27 (2C), 39.57, 38.87, 36.07, 28.28, 2201, 21.23, 18.88, 18.16, 15.19, 14.15, 1.74, 10.14, 8.22.

MS: m/z 629 (M+H).

Example 3 11-Deoxy-5-O-desosaminyl-11-(3-quinolin-4-yl-propylidene)hyd razo-6-O- methvlervthronolide A. 11 .12-carbamate To a solution of 11 -deoxy-5-O-desosaminyl-1 1 -hydrazo-6-O-methyi-erythronolide A, 11,12-carbamate (1.35 g, 21.7 mmol) in anhydrous EtOH (20 mL) was added 3-(4- quinolinyl)propionaldehyde (0.57 g, 3.08 mmol) and the resulting solution was heated at 86~C for two days. EtOH was evaporated in vacuo to give the title compound as a white solid (1.84 g, 97%).

H NMR (400 MHz, CDCl3) 6: 8.81 (1H, d, J = 4.4 Hz), 8.09 (1H, d, J = 5.2 Hz), 8.07 (1H, d, J = 5.2 Hz), 7.69 (1H, t, J = 8.4 Hz), 7.56 (1H, t, J = 7.2 Hz), 7.29 (1H, d, J = 4.0 Hz), 5.08 (1H, dd, J = 2.0, 10.8Hz), 4.53 (1H, s), 4.41 (1H, d, J = 7.6 Hz), 4.2-3.2 (m), 2.99 (3H, s), 2.9-2.4 (m), 2.25 (6H, s), 2.0-1.5 (m), 1.48 (3H, s), 1.29 (3H, s), 1.30 (3H, d, J = 6.4 Hz), 1.24 (3H, d, J = 6.0 Hz), 1.15 (3H, d, J = 6.4 Hz), 1.10 (3H, d, J = 7.2 Hz), 1.07 (3H, d, J = 6.4 Hz), and 0.87 (3H, t, J = 7.2 Hz).

MS: m/z 794 (M+H).

Example 4 2'-Acetyl-11-deoxy-5-O-desosaminyl-11-(3-quinolin-4-yl-propy lidene)hydrazo-6-O- methvlervthronolide A. 11.1 2-carbamate

To a solution of 11 -deoxy-5-O-desosaminyl-1 1 -(3-quinolin-4-yl-propylidene)hydrazo-6- O-methylerythronolide A, 11,12-carbamate (2.07 g, 2.60 mmol) in CH2C12 (10 mL) was added acetic anhydride (0.49 mL, 5.20 mmol) and the resulting solution was stirred at room temperature for 5 hours. Saturated NaHCO3 was added, the aqueous layer was extracted with CH2C12, and the combined organic layers were washed with brine, dried over anhydrous MgSO4, and evaporated in vacuo to give the title compound as a white solid (1.79 g, 82%).

1H NMR (400 MHz, CDC!3) : 8.80 (1H, d, J = 4:4 Hz), 8.08 (1H, d, J = 8.4 Hz), 8.05 (1H, d, J = 9.2 Hz), 8.01 (1H, t, J = 4.8 Hz), 7.68 (1H, dt, J = 1.2, 6.8 Hz), 7.55 (1H, dt, J = 1.2, 6.8 Hz), 7.27 (1H, d, J = 4.4 Hz), 5.02 (1H, dd, J = 2.8, 10 Hz), 4.718 (1H, t, J = 6.7 Hz), 4.40 (1H, s), 4.35 (1H, d, J = 7.6 Hz), 4.19 (1H, d, J = 8.0 Hz), 3.81 (1H, q, J = 6.8 Hz), 3.6-2.4 (m), 2.71 (3H, s), 2.24 (6H, s), 1.9-1.5 (m), 1.55 (3H, s), 1.35 (3H, d, J = 6.8 Hz), 1.33 (3H s), 1.22 (3H, d, J = 6.0 Hz), 1.14 (3H, d, J = 7.6 Hz), 1.10 (3H, d, J = 6.8 Hz), 1.06 (3H, d, J = 6.4 Hz), and 0.87 (3H, t, J = 7.2 Hz).

MS: m/z 837 (M+H).

Example 5 2'-Acetvl-1 1 -deoxv-5-O-desosaminvl-1 1 -(3-auinolin-4-vl-ornoylidene)hvdrnzo-6-O- methvl-3-oxoervthronolide A. 11.12-carbamate To a solution of 2'-acetyl-1 1-deoxy-5-O-desosaminyl-1 1-(3-quinolin-4-yl- propylidene)hydrazo-6-O-methylerythronolide A, 11,12-carbamate (1.69 g, 2.02 mmol) in CH2Cl2 (16 mL) was added DMSO (1.85 mL, 8.06 mmol, 10 eq), 1-ethyl-3-(3- dimethylaminopropyl)carbodiimide (EDAC) (1.55 g, 8.06 mmol, 3.1 eq), and Py"TFA (1.56 g, 8.06 mmol, 3.1 eq) and the resulting suspension was stirred at room temperature for 2 hours.

Saturated NaHCO3 was added, the aqueous layer was extracted with CH2C12 (3 times). The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude product was purified by silica gel flash chromatography (5% MeOH-0.5% NH3"H20-94.5% CH2Cl2) to afford the title compound as a white solid (1.59 g, 94%).

'H NMR (400 MHz, CDC13): 8.79 (1H, d, J = 3.6 Hz), 8.08 (1H, d, J = 8.8 Hz), 8.05 (1H, d, J = 8.4 Hz), 8.00 (1H, t, J = 4.8 Hz), 7.69 (1H, t, J = 8.4 Hz), 7.55 (1H, t, J = 7.2 Hz), 7.27 (1H, d, J = 4.4 Hz), 5.03 (1H, dd, J = 2.4, 10.0 Hz), 4.70 (1H, dd, J = 7.6, 10.4 Hz), 4.39 (1H, s), 4.34 (1H, d, J = 7.6 Hz), 4.18 (1H, d, J = 8.0 Hz), 3.82 (1H, q, J = 6.8 Hz), 3.6-1.6 (m), 2.71 (3H, s), 2.22 (6H, s), 2.03 (3H, s), 1.54 (3H, s), 1.33 (3H, d, J = 6.4 Hz), 1.28 (3H, s), 1.21 (3H, d, J = 6.4 Hz), 1.14 (3H, d, J = 7.6 Hz), 1.09 (3H, d, J = 6.8 Hz), 1.06 (3H, d, J = 6.8 Hz), 0.87 (3H, t, J = 7.2 Hz).

MS: m/z 836 (M+H).

Example 6

11-deoxy-5-O-desosaminyl-11-(3-quinolin-4-yl-propyl))hydrazo -6-O-methyl-3- oxoervthronolide A. 11 .12-carbamate: To a solution of 2'-acetyl-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-quinolin-4-yl- propylidene)hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate (1.59 g, 1.90 mmol) in MeOH (25 mL) at room temperature was added NaBH3CN (359 mg, 5.70 mmol, 3 eq) followed by HOAc (0.65 mL, 11.4 mmol, 6 eq) and the resulting reaction mixture was stirred at room temperature overnight. MeOH was removed in vacuo and the residue was dissolved in CH2C12.

Saturated NaHCO3 was added, the aqueous layer was extracted with CH2C12 (3 times), the combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was dissolved in MeOH (50 mL) and the solution was heated under reflux for 1 hour. MeOH was then removed in vacuo and the crude product was purified by silica gel flash chromatography (5% MeOH-0.5% NH3"H2O-94.5% CH2Cl2) to afford the title compound as a white solid (1.13 g, 75%).

1H NMR (400 MHz, CDCI3) : 8.75 (1H, d, J = 4.27 Hz), 8.07 (2H, t, J = 9.4 Hz), 7.64 (1H. dt, J = 1.6, 6.8 Hz), 7.50 (1H, dt, J = 1.6, 7.2 Hz), 7.26 (1H, d, J = 4.4 Hz), 5.47 (1H, t, J = 3.6 Hz), 4.98 (1H, d, J = 10.8 Hz), 4.26 (1H, s), 4.24 (1H, s), 3.84 (1H, q, J = 6.8 Hz), 3.71 (1H, s), 3.8-2.7(m), 2.62 (3H, s), 2.6-2.3 (m), 2.22 (6H, s), 2.2-1.5 (m), 1.44 (3H, s), 1.33 (3H, d, J = 6.8 Hz), 1.31 (3H, s), 1.29 (3H, d , J = 7.6 Hz), 1.21 (3H, d, J = 6.0 Hz), 1.16 (3H, d, J 6.0 Hz), 1.04 (3H, d, J = 6.8 Hz), and 0.78 (3H, t, J = 7.2 Hz).

53C NMR (100.6 MHz, CDCl3) 8 (attached H's): 217.82 (0), 203.63 (0), 169.72 (0), 156.10 (0), 150.18 (1), 148.20 (2C, 0), 130.05 (1), 128.85 (1), 127.58 (0), 126.19 (1), 123.81 (1), 120.97 (1), 103.96 (1), 80.69 (0), 79.37 (1), 78.12 (0), 77.35 (1), 70.33 (1), 69.63 (1), 65.84 (1), 58.14 (1), 51.04 (1), 50.13 (3), 48.41 (2), 47.31 (1), 44.55 (1), 40.19 (2C, 3), 39.60 (2C, 2 and 1), 29.49 (2), 28.47 (2), 28.14 (2), 22.03 (2), 21.14 (3), 19.82 (3), 18.50 (3), 15.31 (3), 14.55 (3), 14.38 (3), 14.21 (3), and 10.35 (3).

MS: m/z 797 (M+H).

Example 7 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-quinolin-4-yl-propyl) )hydrazo-9- hvdroxvimino-6-O-methvl-3-oxoervthronolide A. 11,12-carbamate Method I: To a solution of 11 -deoxy-5-O-desosaminyl-1 1 -(3-quinolin-4-yl-propyl)hydrazo-6-O methyl-3-oxoerythronolide A, 11,12-carbamate (654 mg, 0.82 mmol) in i-PrOH (8.0 mL) was added NH2OH"HCl (855 mg, 12.3 mmol, 15 eq) and the reaction mixture was heated at 90~C for six days. i-PrOH was removed in vacuo and the residue was dissolved in CH2C12. Saturated NaHCO3 was added, the aqueous layer was extracted with CH2Cl2 (3 times), the combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in

vacuo. The crude product was purified by preparative TLC (10% MeOH-1% NH3.H2O-89% CH2Cl2) to afford the title compound as a white solid (224 mg, 34%) and the recovered starting material (107 mg, 16%).

1H NMR (400 MHz, CDCl3) : 10.85 (1H, brs), 8.39 (1H, d, J = 4.4 Hz), 8.00 (1H, d, J = <BR> <BR> <BR> <BR> 8.4 Hz), 7.90 (1H, d, J = 8.0 Hz), 7.60 (1H, t, J = 7.2 Hz), 7.42 (1H, t, J = 7.6 Hz), 6.82 (1H, d, J = 4.8 Hz), 5.05 (1H, dd, J = 2.0, 10.8 Hz), 4.30 (1H, dd, J = 5.6, 7.2 Hz), 3.89 (1H, q, J = 6.4 Hz), 3.92 (1H, s), 3.55 (1H, m), 3.27 (1H, m), 3.15-2.50 (m), 2.83 (3H, s), 2.35 (6H, s), 1.95 (1H, m), 1.8-1.2 (m), 1.55 (3H, s), 1.49 (3H, s), 1.35 (3H, d, J = 6.8 Hz), 1.29 (3H, d, J = 7.6 Hz), 1.26 (3H, d, J = 6.0 Hz), 1.15 (3H, d, J = 6.8 Hz), 1.03 (3H, d, J = 6.8 Hz), and 0.825 (3H, t, J = 7.2 Hz).

53C NMR (100.6 MHz, CDCl3) 6 (attached H's): 203.73 (0), 169.85 (0), 166.52 (0), 156.35 (0), 149.22 (1), 147.06 (0), 129.35 (1), 128.85 (1), 127.36 (0), 126.41 (1), 123.77 (1), 120.24 (1), 103.91 (1), 81.28 (0), 79.77 (1), 78.66 (0), 77.37 (1), 70.34 (1), 69.40 (1), 65.95 (1), 59.68 (1), 51.16 (1), 50.52 (3), 48.08 (2), 47.52 (1), 40.26 (2C, 3), 38.26 (2), 33.66 (1), 29.40 (2), 28.51 (2), 27.93 (2), 25.59 (1), 22.17 (2), 21.18 (3), 20.09 (3), 19.15 (3), 17.40 (3), 15.37 (3), 14.52 (3), 14.36 (3), and 10.44 (3).

MS: m/z 812 (M+H).

Method II: To a solution of 9-deoxo-1 1-deoxy-5-O-desosaminyl-1 1-(3-quinolin-4-yl- propylidene)hydrazo-9-hydroxyimino-6-O-methyl-3-oxoerythrono lide A, 11,12-carbamate (186 mg, 0.23 mmol), prepared according to the procedures as described in Example 17, in methanol was added HOAc (212 uL, 3.7 mmol) and NaBH3CN (158 mg, 2.3 mmol) and the resulting mixture was stirred at room temperature for 12 h. MeOH was removed in vacuo and the residue was dissolved in CH2CL2. Saturated NaHCO3 was added, the aqueous layer was extracted with CH2Cl2 (3 times), the combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude product was purified by silica gel flash chromatography (5% MeOH-0.5% NH3-H2O-94.5% CH2Cl2) to afford the title compound as a white solid (114 mg, 61%).

Example 8 9-Deoxo-1 1 -deoxv-5-O-desosaminvl-1 1 -(3-Quinoli n4-vl-oro Dvl)) hvdrazo-9- methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate Method I: To a solution of 1 1-deoxy-5-O-desosaminyl-1 1-(3-quinolin-4-yl- propyl)hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate (50 mg, 0.063 mmol) in i- PrOH (1.0 mL) was added NH2OMe"HCl (26 mg, 0.31 mmol, 5 eq) and the reaction mixture was heated at 90~C for three days. CPrOH was removed in vacuo and the residue was

dissolved in CH2Cl2. Saturated NaHCO3 was added, the aqueous layer was extracted with CH2Cl2 (3 times), the combined organic layers were washed with brine, dried over anhydrous Mg SO4, and concentrated in vacuo. The crude product was purified by preparative TLC (10% MeOH-1% NH3"H2O-89% CH2Cl2) to afford the title compound as a white solid (27 mg, 52%) and some recovered starting material.

H NMR (400 MHz, CDCl3) 6: 8.75 (1H, d, J = 4.4 Hz), 8.12 (1H, d, J = 8.4 Hz), 8.06 (1H, d, J = 8.8 Hz), 7.65 (1H, t, J = 6.8 Hz), 7.50 (1H, t, J = 6.8 Hz), 7.27 (1H, d, J = 4.4 Hz), 6.04 (1H, br s), 5.01 (1H, d, J = 9.6 Hz), 4.3-1.4 (m), 3.86 (1H, q, J = 6.8 Hz), 3.70 (3H, s), 2.66 <BR> <BR> <BR> (3H, s), 2.31 (6H, s), 1.45 (3H, s), 1.37 (3H, s), 1.33 (3H, d, J = 6.8 Hz), 1.27 (3H, d, J = 7.2 Hz), 1.24 (3H, d, J = 6.0 Hz), 1.10 (3H, d, J = 6.4Hz), 0.98 (3H, d, J = 6.8 Hz), and 0.77 (3H, t, J = 7.6 Hz).

MS: m/z 826 (M+H).

Method ll: The title compound was prepared from 9-deoxo-11-deoxy-5-O-desosaminyl-11- hydrazo-9-methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate and 3-quinolin-4- yl-propioaldehyde following the procedures as described in Example 11.

Example 9 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-quinolin-4-yl-propyl) )hydrazo-9- benzoxvimino-6-O-methvl-3-oxoervthronolide A. 11.12-carbamate To a solution of 11 -deoxy-5-O-desosaminyl-1 1 -(3-quinolin-4-yl-propyl)hydrazo-6-O- methyl-3-oxoerythronolide A, 11,12-carbamate (40 mg, 0.050 mmol) in i-PrOH (1.0 mL) was added NH2OBn"HCl (32 mg, 0.20 mmol) and the reaction mixture was heated at 90~C for three days. i-PrOH was removed in vacuo and the residue was dissolved in CH2Cl2. Saturated NaHCO3 was added, the aqueous layer was extracted with CH2CI2 (3 times), the combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude product was purified by preparative TLC (10% MeOH-1% NH3"H20-89% CH2C12) to afford the title compound as a white solid (10 mg, 22%) and some recovered starting material.

1H NMR (400 MHz, CDCI3): 8.75 (1H, d, J = 4.4 Hz), 8.10 (1H, d, J = 8.4 Hz), 8.07 (1H, d, J = 8.4 Hz), 7.65 (1H, t, J = 7.2 Hz), 7.49 (1H, t, J = 8.4 Hz), 7.30 (6H, m), 5.82 (1H, br s), 4.99 (1H, d, J = 8.0 Hz), 4.95 (1H, d, J = 12.4 Hz, AB), 4.85 (1H, d, J = 12.4 Hz, AB), 4.3-1.4 (m), 3.86 (1H, q, J = 6.8 Hz), 2.67 (3H, s), 2.30 (6H, s), 1.44 (3H, s), 1.40 (3H, s), 1.33 (3H, d, J = 6.8 Hz), 1.28 (3H, d, J = 7.6 Hz), 1.25 (3H, d, J = 6.0 Hz), 1.07 (3H, d, J = 7.2 Hz), 0.95 (3H, d, J = 6.8 Hz), and 0.75 (3H, t, J = 7.2 Hz).

MS: m/z 902 (M+H).

Example 10 9-Deoxo-11-deoxy-5-O-desosaminyl-11-hydrazo-9-methoxyimino-6 -O-methyl-3- oxoervthronolide A. 11 .12-carbamate To a solution of I 1-deoxy-5-O-desosaminyl-1 1-hydrazo-6-O-methyl-3- oxoerythronolide A, 11,12-carbamate (600 mg, 0.96 mmol) in EtOH (9.0 mL) was added NH2OMe"HCl (319 mg, 3.83 mmol, 4.0 eq) and the reaction mixture was heated at 80~C for 48 hours. EtOH was removed in vacuo and the residue was dissolved in CH2Cl2. Saturated NaHCO3 was added, the aqueous layer was extracted with CH2Cl2 (3 times), the combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo to give the title compound as a white solid (602 mg).

'H NMR (400 MHz, CDCl3) 6: 3.77 (3H, s), 2.68 (3H, s), 2.25 (6H, s), 1.43 (s, 3H), 1.38 (3H, s), 1.33 (3H, d, J = /.2 Hz), 1.27 (3H, d, J = 7.6 Hz), 1.23 (3H, d, J = 6.0 Hz), 1.13 (3H, d, J = 6.8 Hz), 0.98 (3H, d, J = 6.8 Hz), and 0.83 (3H, t, J = 7.6 Hz).

MS: m/z 657 (M+H).

Example 11 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(4-pyridin-3-yl-imida zol-1-yl)-propyl)hydrazo- 9-methoxvimino-6-O-methvl-3-oxoervthronolide A. 11 .12-carbamate To a solution of 9-Deoxo-11-deoxy-5-O-desosaminyl-11-hydrazo-9-methoxyimino-6 -O- methyl-3-oxoerythronolide A, 11,12-carbamate (300 mg, 0.45 mmol) in toluene (4.0 mL) was added 3-(4-pyridin-3-yl-imidazol-1-yl)-propioaldehyde (100 mg, 0.50 mmol, 1.1 eq) and the reaction mixture was heated at 90~C for 18 hours. Toluene was removed in vacuo and the residue was dissolved in MeOH (4.0 mL). HOAc (0.39 mL, 6.8 mmol) and NaBH3CN (427 mg, 6.8 mmol) were added and the resulting solution was stirred at room temperature for 14 hours.

MeOH was evaporated in vacuo, saturated NaHCO3 was added to the residue, the aqueous layer was extracted with CH2Cl2 (3 times), the combined organic layers were washed with brine, dried over an hydros MgSO4, and concentrated in vacuo. The crude product was purified by preparative TLC (10% MeOH-1% NH3"H2O-89% CH2Cl2) to afford the title compound as a white solid.

1H NMR (400 MHz, CDCl3) 6: 8.94 (1H, s), 8.42 (1H), 8.03 (1H), 7.58 (1H, s), 7.36 (1H, s), 7.25 (1H), 6.11 (1H, s), 3.69 (3H, s), 2.64 (3H, s), 2.23 (6H, s), 1.45 (3H, s), 1.36 (3H, s), 1.30 (3H, d, J = 5.6 Hz), 1.26 (3H, d, J = 6.8 Hz), 1.21 (3H, d, J = 4.8 Hz), 1.09 (3H, d, J = 6.8 Hz), 0.97 (3H, d, J = 6.4 Hz), and 0.80 (3H, t, J = 6.4 Hz).

13C NMR (100 MHz, CDCl3) #: 203.41, 170.01, 167.63, 156.73, 147.56, 146.40, 138.94, 138.13, 131.85, 130.31, 123.47, 115.12, 103.99, 81.36, 779.51, 77.27, 70.33, 69.58, 65.84, 61.30, 59.24, 51.06, 50.40, 47.37, 44.39, 44.35, 40.23 (2C), 38.21, 33.86, 29.28, 28.12, 26.48, 22.11, 21.18, 19.91, 18.97, 17.45, 15.19, 14.49, 14.33, and 10.53.

MS: m/z 842 (M+H).

Example 12 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(imidazo(4,5-b)pyridi n-3-yl)-propyl)hydrazo- 9-methoxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate To a solution of 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -hydrazo-9-methoxyimino-6-O- methyl-3-oxoerythronolide A, 11,12-carbamate (2.0 g, 3.05 mmol) in toluene (30 mL) was added 3-(imidazo(4,5-b)pyridin-3-yl)-propioaldehyde (910 mg, 4.26 mmol, 1.4 eq) and the reaction mixture was heated at 99~C for 18 hours. Toluene was removed in vacuo and the residue was dissolved in MeOH (30 mL). HOAc (2.8 mL, 48.72 mmol) and NaBH3CN (1.91 g, 30.45 mmol) were added and the resulting solution was stirred at room temperature for 14 hours. MeOH was evaporated in vacuo, saturated NaHCO3 was added to the residue, the aqueous layer was extracted with CH2CL2 (3 times), the combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude product was purified by preparative TLC (10% MeOH-1% NH3"H20-89% CH2Cl2) to afford the title compound as a white solid.

1H NMR (400 MHz, CDCl3) 6: 8.35 (1H), 8.22 (1H, s), 8.02 (1H), 7.20 (1H) 7.36 (1H, s), 6.10 (1H, brt), 3.47 (3H, s), 2.62 (3H, s), 2.24 (6H, s), 1.46 (3H, s), 1.37 (3H, s), 1.30 (3H, d, J = 6.8 Hz), 1.27 (3H, d, J = 7.6 Hz), 1.22 (3H, d, J = 6.0 Hz), 1.12 (3H, d, J = 6.8 Hz), 0.99 (3H, d, J = 7.2 Hz), and 0.84 (3H, t, J = 7.6 Hz).

MS: m/z 816 (M+H).

Example 13 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(4-phenyl-imidazol-1- yl)-propyl)hydrazo-9- methoxvimino-6-O-methvl-3-oxoervthronolide A. 11.1 2-carbamate To a solution of 9-Deoxo-1 1-deoxy-5-O-desosaminyl-1 I -hydrazo-9-methoxyimino-6-O- methyl-3-oxoerythronolide A, 11,12-carbamate (1.37 g, 2.09 mmol) in toluene (14 mL) was added 3-(4-phenyl-imidazol-1-yl)-propioaldehyde (583 mg; 2.92 mmol, 1.4 eq) and the reaction mixture was heated at 90~C for 18 hours. Toluene was removed in vacuo and the residue was dissolved in MeOH (20 mL). HOAc (1.8 mL, 31.35 mmol) and NaBH3CN (1.97 g, 31.35 mmol) were added and the resulting solution was stirred at room temperature for 14 hours. MeOH was evaporated in vacuo, saturated NaHCO3 was added to the residue, the aqueous layer was extracted with CH2Cl2 (3 times), the combined organic layers were washed with brine, dried over an hydros MgSO4, and concentrated in vacuo. The crude product was purified by preparative TLC (10% MeOH-1% NH3"H2O-89% CH2Cl2) to afford the title compound as a white solid. tH NMR (400 MHz, CDC13) 6: 8.35 (1H), 8.22 (1H, s), 8.02 (1H), 7.20 (1H), 7.36 (1H, s), 6.10 (1H, brt), 3.69 (3H, s), 2.66 (3H, s), 2.26 (6H, s), 1.46 (3H, s), 1.37 (3H, s), 1.32 (3H, d, J = 6.8 Hz), 1.27 (3H, d, J = 7.6 Hz), 1.22 (3H, d, J = 6.0 Hz), 1.11 (3H, d, J = 7.2 Hz), 0.98 (3H, d, J = 7.2 Hz), and 0.83 (3H, t, J = 7.2 Hz).

MS: m/z 841 (M+H).

Example 14 9-Deoxo-11 -deoxv-5-O-desosaminvl-1 O-eni-1 I -hvdrazo-9-benzoxvimino-6-O-methvl-3- oxoervthronolide A. 11.12-carbamate To a solution of 11 -deoxy-5-O-desosaminyl- 1 0-epi-1 I -hydrazo-6-O-methyl-3- oxoerythronolide A, 11,12-carbamate (202 mg, 0.322 mmol) in MeOH (3.0 mL) was added NH2OBn*HCI (225 mg, 1.41 mmol, 4.4 eq) and the reaction mixture was heated at 72~C for 16 hours. MeOH was removed in vacuo and the residue was dissolved in CH2C12. Saturated NaHCO3 was added, the aqueous layer was extracted with CH2CI2 (3 times), the combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude product was purified by preparative TLC (10% MeOH-1% NH3-H2O-89% CH2Cl2) to afford the title compound as a white solid.

H NMR (400 MHz, CDCl3) ~: 7.25 (5H, m), 5.39 (4H, br s), 5.09 (1H, d, J = 12.8 Hz, AB), 4.99 (1H, d, J = 12.8 Hz, AB), 4.93 (1H, dd, J = 3.2, 9.2 Hz), 4.30 (1H, d, J = 7.2 Hz), 3.98 <BR> <BR> <BR> (1H, d, J = 10.8 Hz), 3.54 (1H, q, J = 6.8 Hz), 3.9-1.3 (m), 2.75 (3H, s), 2.27 (6H, s), 2.02 (3H, d, J = 6.8 Hz), 1.30 (3H, s), 1.27 (3H, d, J = 7.2 Hz), 1.22 (3H, s), 1.21 (3H, d, J = 6.8 Hz), 1.20 (3H, d, J = 6.8 Hz), 1.09 (3H, d, J = 7.2 Hz), and 0.814 (3H, t, J = 7.6 Hz).

MS: m/z 733 (M+H).

Example 15 9-Deoxo-1 1 -deoxv-5-desosaminvl-1 o-eDi-1 1-hydrazo-9-hydroxyimino-6-O-methyl-3- oxoerythronolide A, 11,12-carbamate To a solution of 11 -deoxy-5-O-desosaminyl-1 0-epi-1 1 -hydrazo-6-O-methyl-3- oxoerythronolide A, 11,12-carbamate (499 mg, 0.795 mmol) in i-PrOH (7.0 mL) was added NH2OH"HCl (579 mg, 8.33 mmol, 10.5 eq) and the reaction mixture was heated at 80~C for three days. i-PrOH was removed in vacuo and the residue was dissolved in CH2Cl2. Saturated NaHCO3 was added, the aqueous layer was extracted with CH2Cl2 (3 times), the combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude product was purified by preparative TLC (10% MeOH-1% NH3.H2O-89% CH2Cl2) to afford a 3 : 2 mixture of the title compound as a white solid (157 mg, 31%).

H NMR (400 MHz, CDCI3) of the major isomer, o: 2.77 (3H, s, 6-OMe), 2.26 (6H, s, NMe2), 0.84 (3H, t,, J = 7.0 Hz, 15-Me); MS: m/z 610 (M+H).

'H NMR (400 MHz, CDCI3) of the minor isomer, ~: 2.68 (3H, s, 6-OMe), 2.25 (6H, s, NMe2), 0.81 (3H, t,, J = 7.0 Hz, 15-Me); MS: m/z 610 (M+H).

Example 16 9-Deoxo-11-deoxy-5-O-desosaminyl-11-hydrazo-9-hydroxyimino-6 -O-methyl-3-$1 $80~C $CH2Cl2 $NH.H2O-96.7% $CDCl3) oxoervthronolide A. 1 1.1 .12-carbamate To a solution of 1 1-deoxy-5-O-desosaminyl-1 1-hydrazo-6-O-methyl-3- oxoerythronolide A, 11,12-carbamate (20 g, 31.8 mmol) in EtOH (210 mL) was added NH2OH"HCl (33.19, 477 mmol, 15 eq) and pyridine (38.4 mL, 477 mmol, 15 eq), and the resulting solution at 80~C for 38 h. EtOH was removed in vacuo and the residue was dissolved in CH2CI2. Saturated NaHCO3 was added, the aqueous layer was extracted with CH2Cl2 (3 times), the combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude product was purified by silica gel flash chromatography (3% MeOH-0.3% NH3.H2O-96.7% CH2CI2) to afford the title compound as a white solid (7.39). rH NMR (400 MHz, CDCl3) : 9.81 (1H, br. s), 2.67 (3H, s), 2.57 (1H, q, J = 6.8 Hz), 2.25 (6H, s), 1.47 (3H, s), 1.43 (3H, s), 1.32 (3H, d, J = 6.8 Hz), 1.25 (3H, d, J = 7.6 Hz), 1.21 (3H, d, J = 6.4Hz), 1.11 (3H, d, J = 6.8Hz), 0.97 (3H, d, J = 7.2Hz), 0.83 (3H, t, J = 7.2Hz).

13H NHMR (100 MHz, CDCl3) #: 203.81, 169.80, 165.97, 156.68, 103.91, 81.53, 79.85, 78.49, 76.74, 70.35, 69.48, 65.85, 64.33, 51.10, 49.66, 47.73, 40.24, 38.42, 33.73, 28.19, 25.55, 22.11, 21.15,19.98, 18.64, 16.96, 15.68,14.25,13.71, and 10.39.

MS: m/z 643 (M+H).

Example 17 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-quinolin-4-yl-propyli dene)hydrazo-9- hvdroxvimino-6-O-methvl-3-oxoervthronolide A. 11.12-carbamate To a solution of 9-deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -hydrazo-9-hydroxyimino-6-O- methyl-3-oxoerythronolide A, 11,12-carbamate (150 mg, 0.23 mmol) in anhydrous toluene (2.3 mL) was added 3-(4-quinolinyl)propionaldehyde (85 mg, 0.46 mmol) and the resulting solution was heated at 90~C for 18 h. EtOH was evaporated in vacuo and the crude product was purified by silica gel flash chromatography (5% MeOH-0.5% NH3"H2O-94.5% CH2C12) to afford the title compound.

'H NMR (400 MHz, CDC13) 6: 2.84 (3H, s), 2.30 (6H, s), 1.58 (3H, s), 1.54 (3H, s), 1.34 (3H, d, J = 6.8 Hz), 1.32 (3H, d, J = 7.2 Hz), 1.28 (3H, d, J = 6.0 Hz), 1.25 (3H, d, J = 6.0 Hz), 1.05 (3H, d, J = 7.2 Hz), 0.86 (3H, t, J = 7.2 Hz).

MS: m/z 810 (M+H).

Example 18 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-3-benzoimidazol-1-yl- propyl)hydrazo-9- hvdroxvimino-6-O-methvl-3-oxoervthronolide A. 11.12-carbamate To a solution of 9-deoxo-11-deoxy-5-O-desosaminyl-11-hydrazo-9-hydroxyimino-6 -O- methyl-3-oxoerythronolide A, 11,12-carbamate (100 mg, 0.16 mmol) in anhydrous toluene (1.6 mL) was added 3-(benzoimidazol-1-yl)propionaldehyde (62 mg, 0.36 mmol) and the resulting solution was heated at 90~C for 18 h. EtOH was evaporated in vacuo and the crude product was dissolved in methanol (1.5 mL). To this solution was added HOAc (137uL, 2.4 mmol) and NaBH3CN (103 mg, 1.5 mmol) and the resulting mixture was stirred at room temperature for 12 h. MeOH was removed in vacuo and the residue was dissolved in CH2CL2. Saturated NaHCO3 was added, the aqueous layer was extracted with CH2Cl2-(3 times), the combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude product was purified by preparative TLC (10% MeOH-1% NH3"H2O-89% CH2C12) to afford the title compound as a white solid (57 mg, 46%).

1H NMR (400 MHz, CDCl3) 6: 11.00 (1H, brs), 2.71 (3H, s), 2.30 (6H, s), 1.49 (3H, s), 1.47 (3H, s), 1.34 (3H, d, J = 6.8 Hz), 1.28 (3H, d, J = 7.6 Hz), 1.23 (3H, d, J = 6.0 Hz), 1.11 (3H, d, J = 7.2 Hz), 0.99 (3H, d, J = 6.8 Hz), and 0.824 (3H, t, J = 7.2 Hz).

2.84 (3H, s), 2.30 (6H, s), 1.58 (3H, s), 1.54 (3H, s), 1.34 (3H, d, J = 6.8 Hz), 1.32 (3H, d, J = 7.2 Hz), 1.28 (3H, d, J = 6.0 Hz), 1.25 (3H, d, J = 6.0 Hz), 1.05 (3H, d, J = 7.2 Hz), 0.86 (3H, t, J = 7.2 Hz).

13H NMR (100 MHz, CDC13 6: 203.45, 169.92, 166.21, 156.74, 143.31, 142.85, 133.53, 122.90, 122.12, 119.47, 110.23, 103.93, 81.33, 79.87, 78.59, 77.24, 70.29, 69.38, 65.97, 59.68,

51.09, 50.62, 47.45, 44.45, 42.34, 40.26, 38.23, 33.59, 28.49, 27.40, 25.55, 22.18, 21.15, 20.10, 19.11, 17.32, 15.28, 14.53, 14.39, and 10.51.

MS: m/z 801 (M+H).

The following compounds were prepared from 9-deoxo-1 l-deoxy-5-O-desosaminyl-l 1- hydrazo-9-hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate and appropriate aldehydes by using the procedures as described above.

Example 19 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(4-phenyl-imidazol-1- yl-propyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate 1H NMR (400 MHz, CDCl3) 6: 2.69 (3H, s), 2.29 (6H, s), 1.49 (3H, s), 1.47 (3H, s), 1.32 (3H, d, J = 6.8 Hz), 1.27 (3H, d, J = 7.6 Hz), 1.24 (3H, d, J = 6.0 Hz), 1.10 (3H, d, J = 6.8 Hz), 1.00 (3H, d, J = 6.8 Hz), and 0.83 (3H, t, J = 7.2 Hz).

MS: m/z 801 (M+H).

Example 20 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-benzotrizol-2-propyl) hydrazo-9- hvdroxvimino-6-O-methvl-3-oxoervthronolide A. 11.1 2-carbamate 1H NMR (400 MHz, CDCl3) ~: 9.95 (1H, br. s), 1.44 (3H, s), 1.39 (3H, s), 1.25 (6H, d, J = 6.8 Hz), 1.23 (3H, d, J = 6.0 Hz), 1.09 (3H, d, J = 6.8 Hz), 1.03 (3H, d, J = 6.8 Hz), and 0.81 (3H, t, J = 7.6 Hz).

MS: m/z 802 (M+H).

Example 21 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-benzotrizol-1-yl-prop yl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate H NMR (400 MHz, CDCl3) 6: 9.02 (1H, br. s), 6.23 (1 H,. br. s), 2.58 (3H, s), 2.32 (6H, s), 1.47 (6H, s), 1.29 (3H, d, J = 6.8 Hz), 1.26 (3H, d, J = 7.6 Hz), 1.23 (3H, d, J = 6.0 Hz), 1.10 (3H, d, J = 6.8 Hz), 1.01 (3H, d, J = 6.8 Hz), and 0.81 (3H, t, J = 7.2 Hz).

MS: m/z 802 (M+H).

Example 22 9-Deoxo-1 1 -deoxv-5-O-desosaminvl- 11 1-(3-ohenvi Droovl) hvdrazo-9-hvdroxvimino-6-0- methvl-3-oxoervthronolide A. 11 .12-carbamate 1H NMR (400 MHz, CDCl3) ~: 9.59 (1H, br. s), 7.10 (5H, m), 6.55 (1H, br. s), 2.67 (3H, s), 2.24 (6H, s), 1.43 (6H, s), 1.33 (3H, d, J = 6.8 Hz), 1.25 (3H, d, J = 7.2 Hz), 1.21 (3H, d, J = 6.0 Hz), 1.00 (3H, d, J = 6.8 Hz), 0.92 (3H, d, J = 6.4 Hz), and 0.82 (3H, t, J = 7.2 Hz).

13C NMR (100 MHz, CDCl3) o: 203.70, 169.59, 166.73, 156.24, 142.12, 128.42 (2C), 128.20 (2C), 125.62, 103.94, 81.35, 79.63, 78.56, 77.11, 70.36, 69.48, 65.87, 59.50, 51.13, 50.40, 48.02, 47.52, 40.24 (2C), 38.21, 33.60, 33.14, 29.77, 28.21, 25.57, 22.19, 21.15, 20.13, 19.05, 17.13, 15.41, 14.46, 14.29, and 10.49.

MS: m/z 761 (M+H).

Example 23 %9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(4-hydroxyphenyl)-pr opyl))hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12.carbamate H NMR (400 MHz, CDCl3) 6: 6.91 (2H), 6.68 (2H), 6.43 (1H, br. s), 2.67 (3H, s), 2.30 (6H, s), 1.44 (3H, s), 1.43 (3H, s), 1.33 (3H, d, J = 6.8 Hz), 1.25 (3H, d, J = 7.2 Hz), 1.21 (3H, d, J = 6.0 Hz), 1.01 (3H, d, J = 6.8 Hz), 0.92 (3H, d, J = 6.4 Hz), and 0.80 (3H, t, J = 7.2 Hz).

MS: m/z 778 (M+H).

Example 24 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(4-methoxypehyl)-prop yl)hydrazo-9- hvdroxvimino-6-O-methvl-3-oxoervthronolide A. 11.1 2-carbamate H NMR (400 MHz, CDCl3) o: 9.38 (1H, br. s), 7.04 (2H, d, J = 8.4 Hz), 6.74 (2H, d, J = 8.4Hz), 6.44 (1H, br. s), 3.74 (3H, s), 2.67 (3H, s), 2.30 (6H, s), 1.44 (6H, s), 1.33 (3H, d, J = 6.8 Hz), 1.25 (3H, d, J = 7.6 Hz), 1.22 (3H, d, J = 6.0 Hz), 1.01 (3H, d, J = 6.8 Hz), 0.93 (3H, d, J = 6.8 Hz), and 0.82 (3H, t, J = 7.2 Hz).

13H NMR (100 MHz, CDCl3) #: 203.71, 169.58, 167.06, 157.64, 156.30, 134.23, 129.29 (2C), 113.68 (2C), 103.84, 81.33, 79.61, 78.51, 77.16, 70.27, 69.34, 65.98, 59.51, 55.19, 51.12, 50.44, 47.95, 47.45, 40.26 (2C), 38.19, 33.64, 32.29, 30.06, 28.46, 25.55, 22.19, 21.12, 20.09, 19.05, 17.17, 15.34, 14.49, 14.33, and 10.49.

MS: m/z 792 (M+H).

Example 25 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(2-methoxyphenyl)-pro pyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate 1H NMR (400 MHz, CDCl3) o: 8.66 (1H, br. s), 7.13 (2H), 6.82 (2H), 3.80 (3H, s), 2.68 (3H, s), 2.30 (6H, s), 1.45 (3H, s), 1.43 (3H, s), 1.32 (3H, d, J = 6.8 Hz), 1.26 (3H, d, J = 7.6 Hz), <BR> <BR> <BR> 1.22 (3H, d, J = 6.4 Hz), 1.06 (3H, d, J = 6.8-Hz), 0.98 (3H, d, J = 6.4 Hz), and 0.83 (3H, t, J = 7.2 Hz).

13H NMR (100 MHz, CDC13) o: 203.78, 169.59,167.39, 157.04, 156.14, 130.36, 129.29, 126.96, 120.82, 110.49, 103.86, 81.19, 79.16, 78.42, 77.24, 70.27, 69.37, 65.94, 59.88, 55.54, 51.10, 50.56, 48.26, 47.34, 40.24 (2C), 38.22, 33.70, 28.44, 27.83, 27.45, 25.58, 22.19, 21.13, 20.01, 19.07, 17.29, 15.21, 14.50, 14.43, and 10.37.

MS: m/z 792 (M+H).

Example 26 9-Deoxo-1 I 1-deoxv-5-O-desosaminvl-1 1-(benzyl)-hydrazo-9-hydroxyimino-6-O-methyl-3- oxoerythronoide A, 11,12-carabamate tH NMR (400 MHz, CDC13) : 7.95 (1H, br. s), 6.23 (1H, br. s), 2.88 (3H, s), 2.29 (6H, s), 1.51 (3H, s), 1.44 (3H, s), 1.36 (3H, d, J = 6.8 Hz), 1.29 (3H, d, J = 7.6 Hz), 1.25 (3H, d, J = 6.0 Hz), 1.05 (3H, d, J = 6.8 Hz), 0.97 (3H, d, J = 7.2 Hz), and 0.75 (3H, t, J = 7.6 Hz).

MS: m/z 733 (M+H).

Example 27 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(pyridin-4-yl-propyl)hyd razo-9-hydroxyimino-6- O-methvl-3-oxoervthronolide A. 11 .12-carbamate 1H NMR (400 MHz, CDCI3) a: 8.07 (2H), 7.25 (2H), 6.39 (1H, br. s), 2.87 (3H, s), 2.27 (6H, s), 1.54 (3H, s), 1.46 (3H, s), 1.34 (3H, d, J = 6.8 Hz), 1.29 (3H, d, J = 7.2 Hz), 1.24 (3H, d, J =6.0 Hz), 1.14 (3H, d, J = 6.8 Hz), 1.01 (3H, d, J = Hz), 0.76 (3H, t, J = 7.2 Hz).

53C NMR (100 MHz, CDCI3) 8: 203.72, 169.91, 166.50, 155.76, 148.16 (2C), 147.70, 123.71 (2C), 103.99, 81.17, 79.75, 78.71, 77.26, 70.34, 69.50, 65.92, 60.30, 51.69, 51.15, 50.74, 47.62, 40.26 (2C), 38.25, 33.69, 28.29, 25.54, 22.02, 21.16, 20.16, 19.14, 17.36, 15.42, 14.50, 14.29, and 10.27.

MS: m/z 733 (M+H).

Example 28 9-Deoxo-11-deoxy-5-O-desosaminyl-11-3-(pyridin-4-yl-propyl)h ydrazo-9-hydroxymino 6-O-methyl-3-oxoerythronolide A, 11,12-carbamate 1H NMR (400 MHz, CDCl3) 8:11.62 (1H, s), 8.24 (2H), 6.91 (2H), 6.20 (1H, br. s), 2.76 <BR> <BR> <BR> (3H, s), 2.31 (6H, s), 1.51 (3H, s), 1.46 (3H, s), 1.33 (3H, d, J = 6.4 Hz), 1.27 (3H, d, J = 7.2 Hz), 1.23 (3H, d, J = 6.0 Hz), 1.10 (3H, d, J = 6.8 Hz), 1.00 (3H, d, J = 6.8 Hz), 0.83 (3H, t, J = 7.2 Hz).

13C NMR (100 MHz, CDCl3) 8:203.71,169.78,166.30, 156.35, 152.39, 140.45, 124.10 (2C), 124.10 (2C), 103.86, 3, 79.71, 78.59, 77.24, 70.27, 69.34, 65.98, 59.50, 51.15, 50.44, 47.55 (2C), 40.27 (2C), 38.21, 33.60, 32.50, 28.54, 27.90, 25.51, 22.14, 21.13, 20.11, 19.11, 17.33, 15.42, 1 14.48, 14.32, and 10.44.

MS: m/z 762(M+H).

Example 29

9-Deoxo-11-deoxy-5-O-desosaminyl-11-3-(pyridin-3-yl-propyl)) hydrazo-9- 6-O-methvl-3-oxoervthronolide A. 11.12-carbamate rH NMR (400 MHz, CDCI3) 3:10.96 (1H, s), 8.30 (1H, d, J = 4.4 Hz), 8.21 (1H, s), 7.40 (1H, d, J = 8.0 Hz), 7.10 (1H, dd, J = 5.2 and 7.6 Hz), 6.16 (1H, br. s), 2.70 (3H, s), 2.27 (6H, s), 1.48 (3H, s), 1.44 (3H, s), 1.31 (3H, d, J = 7.2 Hz), 1.25 (3H, d, J = 7.6 Hz), 1.21 (3H, d, J = 6.0 Hz), 1.06 (3H, d, J = 6.8 Hz), 0.96 (3H, d, J = 6.8 Hz), 0.80 (3H, t, J = 7.6 Hz).

MS: m/z 762(M+H).

Example 30 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(phenylethyl)hydrazo-9-h ydroxyimino-6-O- methyl-3-oxoerythronolide A, 11,12-carbamate 1H NMR (400 MHz, CDCl3) o:7.25 (5H, m), 2.59 (3H, s), 2.28 (6H, s), 1.40 (3H, s), 1.32 (3H, d, J = 6.8Hz), 1.30 (3H, s), 1.25 (3H, d, J = 7.6 Hz), 1.22 (3H, d, J = 6.0 Hz), 0.98 (3H, d, J = 6.8 Hz), 0.88 (3H, d, J = 6.8 Hz), 0.83 (3H, t, J = 7.6 Hz).

MS: m/z 747 (M+H).

Example 31 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(4-methoxyphenyl)-(1, 2,4)oxadizol-5-yl)- propyl)hydrazo-9-hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate 1H NMR (400 MHz, CDCl3) o: 9.65 (1H, br. s), 7.87 (2H, d, J = 8.4 Hz), 6.92 (2H, d, J = 9.2 Hz), 6.16 (1H, br. s), 3.80 (3H, s), 2.46 (3H, s), 2.24 (6H, s), 1.03 (3H, d, J = 7.2 Hz), 0.96 (3H, d, J = 7.2 Hz), and 0.81 (3H, t, J = 7.2 Hz).

MS: m/z 859 (M+H).

Example 32 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(4-chlorophenyl)-(1,2 ,4)oxadizol-5-yl)- propyl)hydrazo-9-hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate H NMR (400 MHz, CDCl3) o: 7.89 (2H, d, J = 8.8 Hz), 7.39 (2H, d, J = 8.8 Hz), 6.20 (1H, br. s), 2.49 (3H, s), 2.24 (6H, s), 1.42 (3H, s), 1.03 (3H, d, J = 7.2 Hz), 0.96 (3H, d, J = 6.8 Hz), and 0.82 (3H, t, J = 7.2 Hz).

MS: m/z 863 (M+H).

Example 33 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-indol-1-yl-propyl)hyd razo-9-hydroxyimino-6- O-methvl-3-oxoervthronolide A. II .12-carbamate 1H NMR (400 MHz, CDCl3) ~: 8.63 (1H, br. s), 8.02 (1H), 7.28 (1H), 7.12 (1H), 7.04 (1 H), 6.89 (1H), 6.23 (1H, br. s), 2.60 (3H, s), 2.30 (6H, s), 1.44 (3H, s), 1.39 (3H, s), 1.34 (3H, d, J = 6.8 Hz), 1.25 (3H, d, J = 7.6 Hz), 1.22 (3H, d, J = 6.4 Hz), 1.02 (3H, d, J = 7.2 Hz), 0.92 (3H, d, J = 6.8 Hz), and 0.82 (3H, t, J = 7.6 Hz).

MS: m/z 800 (M+H).

Example 34 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-indazol-1-yl-propyl)h ydrazo-9-hydroxyimino- 6-O-methyl-3-oxoerythronolide A, 11,12-carbamate 'H NMR (400 MHz, CDCl3) 8:10.53 (1H, br. s), 7.91 (1H), 7.68 (1H), 7.44 (1H), 7.26 (1H), 7.12 (1H), 6.40 (1H, br. s), 2.54 (3H, s), 2.25 (6H, s), 1.48 (3H, s), 1.44 (3H, s), 1.08 (3H, d, J = 6.8 Hz), 1.02 (3H, d, J = 7.2 Hz), and 0.79 (3H, t, J = 7.2 Hz).

MS: m/z 801 (M+H).

Example 35 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(5-phenyl-1H-pyrrol-2 yl)propyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate 1H NMR (400 MHz, CDCl3) ~: 9.36 (1H, br. s), 7.49 (2H), 7.30 (2H), 7.10 (1H), 6.35 (1H), 5.88 (1H), 2.66 (3H, s), 2.25 (6H, s), 1.45 (3H, s), 1.38(3H, s), 1.32 (3H, d, J = 6.8 Hz), 1.25 (3H, d, J = 7.6 Hz), 1.18 (3H, d, J = 6.4 Hz), 1.05 (3H, d, J = 6.8 Hz), 0.93 (3H, d, J = 7.2 Hz), and 0.72 (3H, t, J = 7.2 Hz).

13H NMR (100 MHz, CDCl3) #: 203.54, 169.84, 167.07, 156.85, 133.90, 133.21, 130.84, 128.58, 125.11, 123.35, 106.83, 105.41, 103.89, 81.18, 79.60, 78.52, 77.17, 70.27, 69.37, 65.90, 59.84, 51.12, 50.52, 47.76, 47.49, 40.23, 38.17, 33.64, 28.56, 28.36, 25.57, 25.01, 22.22, 21.12, 20.00, 19.04, 17.19, 15.37, 14.48, 14.28, and 10.39.

MS: m/z 826 (M+H).

Example 36 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-carabazol-9-yl-propyl )hadrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate 1H NMR (400 MHz, CDCl3) o: 7.98 (2H), 7.46 (2H), 7.38 (2H), 7.12 (2H), 2.55 (3H, s), 2.23 (6H, s), 1.44 (3H, s), 1.40(3H, s), 1.35 (3H, d, J = 7.2 Hz), 1.03 (3H, d, J = 6.8 Hz), 0.94 (3H, d, J = 6.8 Hz), and 0.76 (3H, t, J = 7.2 Hz).

MS: m/z 851 (M+H).

Example 37 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(1H-indol-3-yl)-propy l)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate XH NMR (400 MHz, CDCI3) o: 8.75 (1H, br. s), 7.98 (1H), 7.55 (1H), 7.25 (1H), 7.12 (1H), 7.05 (1H), 6.86 (1H), 6.21 (1H, br. s), 2.58 (3H, s), 2.26 (6H, s), 1.44 (3H, s), 1.39(3H, s), 1.34 (3H, d, J = 6.0 Hz), 1.01 (3H, d, J = 6.4 Hz), 0.92 (3H, d, J = 6.8 Hz), and 0.81 (3H, t, J = 7.2 Hz).

MS: m/z 800 (M+H).

Example 38 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-furan-2-yl-propyl)hyd razo-9-hydroxyimino-6- O-methyl-3-oxoerythronolide A, 11,12-carbamate 1H NMR (400 MHz, CDCl3) ~: 9.18 (1H, br. s), 7.21 (1H, s), 5.93 (1H, s), 6.42 (1H, br. s), 5.93 (1H, s), 2.68 (3H, s), 2.25 (6H, s), 1.45 (3H, s), 1.44 (3H, s), 1.32 (3H, d, J = 6.4 Hz), 1.26 (3H, d, J = 7.2 Hz), 1.21 (3H, d, J = 6.4 Hz), 1.01 (3H, d, J = 6.8 Hz), 0.93 (3H, d, J = 6.8 Hz), and 0.83 (3H, t, J = 7.2 Hz).

'3H NMR (100 MHz, CDCl3) ~: 203.71, 169.61, 167.70, 156.30, 155.74, 140.73, 110.02, 104.94, 103.94, 81.34, 79.65, 78.51, 77.11, 70.34, 69.51, 65.86, 59.55, 51.11, 50.44, 47.61, 47.50, 40.25 (2C), 38.20, 33.60, 28.16, 26.22, 25.58, 25.22, 22.19, 21.17, 20.14, 19.07, 17.13, 15.39, 14.47,14.33, and 10.47.

MS: m/z 751 (M+H).

Example 39 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-pyrrol-1-yl-propyl)hy drazo-9-hydroxyimino-6- O-methyl-3-oxoerythronolide A, 11,12-carbamate 1H NMR (400 MHz, CDCl3) ~: 8.51 (1H, br. s), 7.21 (1H, s), 6.64 (1H), 6.05 (1H), 2.68 <BR> <BR> <BR> (3H, s), 2.33 (6H, s), 1.45 (3H, s), 1.43 (3H, s), 1.32 (3H, d, J = 6.4 Hz), 1.26 (3H, d, J = 7.2 Hz), <BR> <BR> <BR> 1.23 (3H, d, J = 6.0 Hz), 1.01 (3H, d, J = 6.8 Hz), 0.93 (3H, d, J = 7.2 Hz), and 0.84 (3H, t, J = 7.2 Hz).

MS: m/z 750 (M+H).

Example 40 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-pyrazol-1-yl-propyl)h ydrazo-9-hydroxyimino- 6-O-methvl-3-oxoervthronolide A. 11,12-carbamate 1H NMR (400 MHz, CDCl3) 8:10.83 (1H, br. s), 7.40 (1H), 7.28 (1H), 6.20 (1H), 6.05 (1H), 2.52 (3H, s), 2.24 (6H, s), 1.45 (3H, s), 1.43 (3H, s), 1.28 (3H, d, J = 6.4 Hz), 1.24 (3H, d, J = 7.6 Hz), 1.19 (3H, d, J = 6.4 Hz), 1.05 (3H, d, J = 6.8 Hz), 0.99 (3H, d, J = 6.8 Hz), and 0.80 (3H, t, J = 7.2 Hz).

MS: m/z 751 (M+H).

Example 41 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-naphthalen-1-yl-propy l)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate 'H NMR (400 MHz, CDCl3) : 9.32 (1H, br. s), 8.04 (1 H), 7.76 (1 H), 7.61(1 H), 7.40 (2H), 7.24 (2H), 2.65 (3H, s), 2.31 (6H, s), 1.44 (3H, s), 1.42 (3H, s), 1.34 (3H, d, J = 6.8 Hz), 1.25 (3H, d, J = 7.6 Hz), 1.23 (3H, d, J = 6.0 Hz), 1.02 (3H, d, J = 6.8 Hz), 0.94 (3H, d, J = 6.8 Hz), and 0.79 (3H, t, J = 7.6 Hz).

MS: m/z 811 (M+H).

The following compounds can be prepared from 9-deoxy-11-deoxy-5-O-desosaminyl-11- hydrazo-9-hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate and appropriate aldehydes by using the procedures as described as above.

9-Deoxo- 11 -deoxy-5-O-desosaminyl-1 1 -(3-(4-phenyl- 1 H-imidazol-2-yl)-propyl) hydrazo- 9-hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-(2-pyridin-3-yl-thiazol-4-yl)-propyl) hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11 ,12-carbamate; 9-Deoxo-11-deoxy-5-O-desosaminyl-11-(3-(2-phenyl-thiazol-5-y l)-propyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,1 2-carbamate; 9-Deoxo-1 1 -deoxy-5-O-desosaminyl-1 1 -(3-thiophen-2-yl-propyl) hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate; 9-Deoxo- 11 -deoxy-5-O-desosaminyl- 11 (3-(7-methoxy-quinolin-4-yl)-propyl)hydrazo-9- hydroxyimino-6-O-methyl-3-oxoerythronolide A, 1 11 ,12-carbamate.