Provided herein are improved processes for converting C7-amino-substituted tetracyclines to C7-fluoro-substituted tetracyclines, as well as intermediates produced by or used in these processes. In one embodiment, a thermal fluorination method is provided in which a suspension comprising a non-polar organic solvent and a C7-diazo-substituted tetracycline hexafluorophosphate, hexafluoroarsenate or hexafluorosilicate salt, or a salt, solvate or combination thereof, is heated to provide a C7-fluoro-substituted tetracycline, or salt, solvate or combination thereof. In another embodiment, a photolytic fluorination is provided in which a solution comprising an ionic liquid and a C7-diazo-substituted tetracycline tetrafluoroborate, hexafluorophosphate, hexafluoroarsenate or hexafluorosilicate salt, or a salt, solvate or combination thereof, is irradiated to provide a C7-fluoro-substituted tetracycline, or salt, solvate or combination thereof.

The present invention provides compounds, compositions thereof, and methods of using the same.

The present invention provides compounds, compositions thereof, and methods of using the same.

A topical therapeutic hydrophobic breakable composition includes a carrier comprising (a) about 60% to about 99% by weight of at least one hydrophobic oil; (b) at least one viscosity-modifying agents selected from the group consisting of a fatty alcohol, a fatty acid and a wax; and (c) a tetracycline antibiotic, characterized in that at least part of the tetracycline antibiotic is suspended in the composition; the viscosity of the composition is at least about 30% higher than the viscosity of the carrier without the tetracycline antibiotic; and is higher than the viscosity or the hydrophobic oil and the tetracycline antibiotic without the viscosity modifying agents. The tetracycline is chemically stable in the composition for at least six months; wherein more than about 90% of the tetracycline has not broken down. The composition is packaged as a breakable foam that breaks easily upon application of shear force.

The present invention is directed to a compound represented by Structural Formula (I): ##STR00001##
or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (I) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (I), or a pharmaceutically acceptable salt thereof, and its therapeutic use.

The present invention is directed to a compound represented by Structural Formula (I): ##STR00001##
or a pharmaceutically acceptable salt thereof. The variables for Structural Formula (I) are defined herein. Also described is a pharmaceutical composition comprising the compound of Structural Formula (I), or a pharmaceutically acceptable salt thereof, and its therapeutic use.

Methods and compositions for using a tetracycline compound to treat bacterial infections are described. In one embodiment, for example, the invention provides a method of treating a subject for an infection, comprising administering to said subject an effective amount of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline or a salt thereof, such that said subject is treated, wherein the 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline is administered orally at a dose of about 450 mg per day for two consecutive days, then at a dose of about 300 mg per day for 5 or more days.

Methods and compositions for using a tetracycline compound to treat bacterial infections are described. In one embodiment, for example, the invention provides a method of treating a subject for an infection, comprising administering to said subject an effective amount of 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline or a salt thereof, such that said subject is treated, wherein the 9-[(2,2-dimethyl-propyl amino)-methyl]-minocycline is administered orally at a dose of about 450 mg per day for two consecutive days, then at a dose of about 300 mg per day for 5 or more days.

The present invention is directed to a compound represented by Structural Formula (I):

##STR00001##

or a pharmaceutically acceptable salt thereof. The variables for Structural Formula I are defined herein.

Also described is a pharmaceutical composition comprising the compound of Structural Formula I and its therapeutic use.

The present invention is directed to a compound represented by Structural Formula (I):

##STR00001##

or a pharmaceutically acceptable salt thereof. The variables for Structural Formula I are defined herein.

Also described is a pharmaceutical composition comprising the compound of Structural Formula I and its therapeutic use.