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.

A crystalline mono hydrochloride salt of (4S,4aS,5aR, 12aS)-4-dimethylamino-3,10,12,12a-tetrahydroxy-7-[(methoxy(methyl)amino)-methyl]-1, 11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-naphthacene-2-carboxylic acid amide is disclosed having improved stability. In addition, a crystalline mono mesylate salt and crystalline mono sulfate salt of (4S,4aS,5aR,12aS)-4-dimethylamino-3, 10,12,12a-tetrahydroxy-7-[(methoxy(methyl)amino)-methyl]-1,11-dioxo-1, 4,4a,5,5a,6,11,12a-octahydro-naphthacene-2-carboxylic acid amide are also disclosed having improved stability. A pharmaceutical composition containing the crystalline salts and methods of treating inflammatory skin disorders and bacterial infections comprising administering the crystalline salts are also disclosed.

A method for synthesizing 9-aminomethyl tetracycline compounds is disclosed. The method comprises a) reacting minocycline and an hydroxymethylamide derivative to form a 2,9-(methylamide-substituted) minocycline and a 2-(methylamidesubstituted) minocycline; b) reacting the 2,9-(methylamide-substituted) minocycline from step a) and an amine or diamine to form a 9-aminomethyl tetracycline intermediate; and c) reacting the 9-aminomethyl tetracycline intermediate from step b) and an aldehyde in the presence of a reducing agent to form a 9-aminomethyl tetracycline compound; or d) reacting the 9-aminomethyl tetracycline intermediate from step b) and an alkyl halide or an alkyl reagent to form a 9-aminomethyl tetracycline compound. Step b) may be operated in the absence of a hydrogenation reaction. The method may be a semi continuous or continuous flow process.

Provided herein are improved processes for convening C7-amino-substituted tetracylines 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, hexafluoarsenate or hexafluorosilicate salt, or a salt, solvate or combination thereof, is healed to provide a C7-fluoro-substituted tetracyline, or salt, solvate or combination thereof. In another embodiment, a photolytic fluorination is provided in which a solution comprising an ionic liquid and a C-7diazo-substituted tetracyline tetrafluoroborate, hexafluorophosphate, hexafluoroarsenate or hexafluorosilicate salt, or a salt, solvate or combination thereof, is irradiated to provide a C7-fluoro-substituted tetracyline, or salt, solvate or combination thereof.

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.

An organic electroluminescence device having a layer of an organic light emitting medium which comprises (A) a specific arylamine compound and (B) at least one compound selected from specific anthracene derivatives, spirofluorene derivatives, compounds having condensed rings and metal complex compounds and is disposed between a pair of electrodes and an organic light emitting medium comprising the above components (A) and (B) are provided. The organic electroluminescence device exhibits a high purity of color, has excellent heat resistance and a long life and efficiently emits bluish to yellowish light. The organic light emitting medium can be advantageously used for the organic electroluminescence device.

An organic electroluminescence device having a layer of an organic light emitting medium which comprises (A) a specific arylamine compound and (B) at least one compound selected from specific anthracene derivatives, spirofluorene derivatives, compounds having condensed rings and metal complex compounds and is disposed between a pair of electrodes and an organic light emitting medium comprising the above components (A) and (B) are provided. The organic electroluminescence device exhibits a high purity of color, has excellent heat resistance and a long life and efficiently emits bluish to yellowish light. The organic light emitting medium can be advantageously used for the organic electroluminescence device.

Crystalline forms, including salts and polymorphs, of a compound useful in the treatment of tetracycline compound-responsive states are provided herein. The crystalline compounds are useful for the treatment or prevention of conditions and disorders such as bacterial infections and neoplasms, as well as other known applications for tetracycline compounds in general.

The present disclosure is directed to compositions and methods which utilize the tetracycline scaffold, preferably the scaffold of tetracycline or minocycline, and which significantly lack antibiotic activity. The compounds have neuroprotective attributes without interfering with the drugs capacity to pass through the blood brain barrier. These compounds have neuroprotective activity because of their inhibition of neuronal cell cycle progression. The compounds are characterized in part by a fifth ring joining positions 9 and 10.

A method of treating Alcohol Use Disorder (AUD), Substance Use Disorder (SUD), tobacco use, pain, or proinflammatory disorders comprising: providing a subject with an effective amount of a modified tetracycline or derivative thereof to ameliorate or eliminate the AUD, SUD, tobacco use, pain, or proinflammatory disorder, and wherein the modified tetracycline or derivative thereof has reduced binding to a microbial ribosome and has the formula: ##STR00001##
wherein R1 is acetyl, R2 is OH or acetyl, R3 is acetyl, R4 is H or acetyl, and R5 is acetyl.