Claims
- 1. A compound of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein:X1 is O, —CR13R14— or —NR4—; X2 is ═O or ═NOR1; R1 is H, methyl or ethyl; R2 is —C(R7)(R8)C(R9)(R10)C(R11)(R12)(4-10 membered heterocyclic) or —(CR7R8)r(C3-C7 cycloalkylene)(CR9R10)q(4-10 membered heterocyclic), wherein q and r are each integers independently ranging from 0 to 2, and the heterocyclic moiety of the foregoing groups is substituted by —(CR4R5)t(4-10 membered heterocyclic) or —(CR4R5)t(C6-C10 aryl) wherein t is an integer from 0 to 5, and the aryl and heterocyclic moietes of each of the foregoing groups are optionally substituted by 1 to 4 R3 groups; each R3 is independently selected from the group consisting of halo, cyano, nitro, trifluoromethyl, trifluoromethoxy, azido, —C(O)R5, —C(O)OR5, —OC(O)R5, —NR5C(O)R4, —C(O)NR4R5, —NR4R5, hydroxy, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C6-C10 aryl, 4-10 membered heterocyclic, and C1-C6 alkoxy; each R4 and R5 is independently selected from H and C1-C6 alkyl; R6 is H or —C(O)(C1-C6 alkyl); R7, R8, R9, R10, R11, R12, R13 and R14 are each independently selected from H, halo and C1-C6 alkyl, provided that (a) where X1 is —CR13R14— and R2 is —C(R7)(R8)C(R9)(R10)C(R11)(R12)(4-10 membered heterocyclic), at least one of R7, R8, R9, R10, R11, R12, R13 and R14 is halo or C1-C6 alkyl, and (b) where X1 is —NR4— and R2 is —C(R7)(R8)C(R9)(R10)C(R11)(R12)(4-10 membered heterocyclic), at least one of R7, R8, R9, R10, R11, and R12 is halo or C1-C6 alkyl; or R7 and R8 are taken together with the carbon to which each is attached to form a C3-C7 cycloalkyl group and R9, R10, R11, R12, R13 and R14 are each independently selected from H, halo and C1-C6 alkyl; or R9 and R10 are taken together with the carbon to which each is attached to form a C3-C6 cycloalkyl group and R7, R8, R11, R12, R13 and R14 are each independently selected from H, halo and C1-C6 alkyl; or R11 and R12 are taken together with the carbon to which each is attached to form a C3-C7 cycloalkyl group and R7, R8, R9, R10, R13 and R14 are each independently selected from H, halo and C1-C6 alkyl; R15 is C1-C6 alkyl; and R16 is H or C1-C10 alkyl.
- 2. A compound according to claim 1 wherein X2 is ═NOR1, R15 is methyl, R16 is ethyl, R6 is H or acetyl, X1 is —NR4— and R2 is —C(R7)(R8)C(R9)(R10)C(R11)(R12)(4-10 membered heterocyclic) wherein said heterocyclic group is substituted by 4-10 membered heterocyclic and the foregoing heterocyclic moieties are optionally substituted by 1 or 2 substituents independently selected from halo and C1-C3 alkyl.
- 3. A pharmaceutical composition for the treatment of a disorder selected from a bacterial infection, a protozoal infection, and a disorder related to a bacterial infection or protozoal infection in a mammal, fish, or bird which comprises a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable carrier.
- 4. A method of treating a disorder selected from a bacterial infection, a protozoal infection, and a disorder related to a bacterial infection or protozoal infection in a mammal, fish, or bird which comprises administering to said mammal, fish or bird a therapeutically effective amount of a compound of claim 1.
- 5. A compound selected from the group consisting essentially of:11-Deoxy-5-O-desosaminyl-11-(3,3-dimethyl-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(3(R)-methyl-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(3(R)-ethyl-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(3(S)-methyl-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(3(S)-ethyl-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2-(1-(4-pyridin-3-yl-imidazol-1-yl)-cyclopropyl)-ethyl)hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2-(1-(4-pyridin-3-yl-imidazol-1-yl)-cyclobutyl)-ethyl)hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2,2-dimethyl-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2,2-diethyl-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2,2-difluro-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2,2-dichloro-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2,2-dibromo-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(1-(4-pyridin-3-yl-imidazol-1-yl-methyl)-cyclopropyl)-methyl-hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(1-(4-pyridin-3-yl-imidazol-1-yl-methyl)-cyclobutyl)-methyl-hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2(R)-methyl-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2(R)-ethyl-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2(S)-methyl-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2(S)-ethyl-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2(R)-fluro-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; 11-Deoxy-5-O-desosaminyl-11-(2(S)-flurol-3-(4-pyridin-3-yl-imidazol-1-yl-propyl))hydrazo-6-O-methyl-3-oxoerythronolide A, 11,12-carbamate, 9-E-(O-methyl)oxime; and the pharmaceutically acceptable salts and solvates of the foregoing compounds.
- 6. A compound of the formula or a pharmaceutically acceptable salt or solvate thereof, wherein:X1 is O, —CR13R14— or —NR4—; X2 is ═O or ═NOR1; R1 is H, methyl or ethyl; R2 is —C(R7)(R8)C(R9)(R10)C(R11)(R12)(4-pyridin-3-yl-imidazol-1-yl) R6 is H or —C(O)(C1-C6 alkyl); R7, R8, R9, R10, R11, R12, R13 and R14 are each independently selected from H, halo and C1-C6 alkyl, provided that (a) where X1 is —CR13R14— and R2 is —C(R7)(R8)C(R9)(R10)C(R11)(R12)(4-10 membered heterocyclic), at least one of R7, R8, R9, R10, R11, R12, R13 and R14 is halo or C1-C6 alkyl, and (b) where X1 is —NR4— and R2 is —C(R7)(R8)C(R9)(R10)C(R11)(R12)(4-10 membered heterocyclic), at least one of R7, R8, R9, R10, R11, and R12 is halo or C1-C6 alkyl; or R7 and R8 are taken together with the carbon to which each is attached to form a C3-C7 cycloalkyl group and R9, R10, R11, R12, R13 and R14 are each independently selected from H, halo and C1-C6 alkyl; or R9 and R10 are taken together with the carbon to which each is attached to form a C3-C6 cycloalkyl group and R7, R8, R11, R12, R13 and R14 are each independently selected from H, halo and C1-C6 alkyl; or R11 and R12 are taken together with the carbon to which each is attached to form a C3-C7 cycloalkyl group and R7, R8, R9, R10, R13 and R14 are each independently selected from H, halo and C1-C6 alkyl; R15 is C1-C6 alkyl; and R16 is H or C1-C10 alkyl.
- 7. A compound according to claim 6, wherein X1 is —NH— and R2 is —C(R7)(R8)C(R9)(R10)C(R11)(R12)(4-pyridin-3-yl-imidazol-1-yl).
- 8. A compound according to claim 7 wherein R7, R8, R9 and R10 are each H, R11 is methyl or ethyl, and R12 is H, methyl or ethyl.
- 9. A compound according to claim 7 wherein R7, R8, R11 and R12 are each H, R9 is methyl or ethyl, and R10 is H, methyl or ethyl.
- 10. A compound according to claim 7 wherein R9, R10, R11 and R12 are each H, R7 is methyl or ethyl, and R8 is H, methyl or ethyl.
Parent Case Info
This application claims benefit of provisional application Ser. No. 60/111,728 filed Dec. 10, 1998.
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Provisional Applications (1)
|
Number |
Date |
Country |
|
60/111728 |
Dec 1998 |
US |