Pyrazolylbenzothiazole derivatives and their use as therapeutic agents

A method for treating a cutaneous inflammatory condition in a patient comprising topically applying a therapeutically effective amount of a topical composition comprising a dermatologically acceptable excipient and a compound of Formula (1):

• as a single tautomer, a mixture of tautomers, a single stereoisomer, a mixture of stereoisomers, or a racemic mixture;
• or a pharmaceutically acceptable salt thereof;
• wherein:
• R1 at each occurrence is independently selected from amino, aminosulfinyl, aminosulfonyl, aryl, azido, halogen, heteroalkyl, heteroaryl, hydrazinyl, hydrocarbyl, hydrogen, hydroxyl, nitro, nitroso, phosphate, phosphinate, phosphonate, phosphonium, phosphorothioate, phosphoryl, sulfamoyl, sulfate, sulfinic acid, sulfonamido, sulfonate, sulfonic acid, sulfoxido, thiol, thioureido, and ureido;
• R2 is amino, aminosulfinyl, aminosulfonyl, azido, halogen, heteroaryl, hydrazinyl, hydroxyl, nitro, nitroso, phosphate, phosphinate, phosphonate, phosphonium, phosphorothioate, phosphoryl, sulfamoyl, sulfate, sulfinic acid, sulfonamido, sulfonate, sulfonic acid, sulfoxido, thiol, thioureido, or ureido;
• R3 is hydrogen, heteroalkyl, heterocycle, halogen-substituted hydrocarbyl, hydrocarbyl, or —O-hydrocarbyl;
• and
• R4 is hydrogen, heteroalkyl, heteroaryl, or hydrocarbyl,
• and wherein heteroalkyl is selected from amido, carboxylic acid, cyano, dihydrocarbylamido, dihydrocarbylamino, di(hydrocarbyl)phosphido, formyl, hydrocarboyloxy, hydrocarbylamino, hydrocarbyloxy, hydrocarbylsiloxy, hydrocarbylsilylamino, hydrocarbylsulfido, hydrocarbylthio, hydrocarbylamido, isothiocyanate, N-heterocycle, perfluorohydrcarbyl, thiocyanate, and hydrocarbyl substituted with one or more groups selected from alkylamino, amino, aminosulfinyl, aminosulfonyl, azido, dialkylamino, halogen, heteroalkyl, heteroaryl, hydrazinyl, hydroxyl, nitro, nitroso, phosphate, phosphinate, phosphonate, phosphonium, phosphorothioate, phosphoryl, sulfamoyl, sulfate, sulfinic acid, sulfonamido, sulfonate, sulfonic acid, sulfonyl, sulfoxido, thiol, thioureido, and ureido.

A method for treating a cutaneous inflammatory condition in a patient comprising topically applying a therapeutically effective amount of a topical composition comprising a dermatologically acceptable excipient and a compound of formula (2):

• as a single tautomer, a mixture of tautomers, a single stereoisomer, a mixture of stereoisomers, or a racemic mixture;
• or a pharmaceutically acceptable salt or solvate thereof;
• wherein:
• R1 at each occurrence is independently selected from amino, aminosulfinyl, aminosulfonyl, aryl, azido, halogen, heteroalkyl, heteroaryl, hydrazinyl, hydrocarbyl, hydrogen, hydroxyl, nitro, nitroso, phosphate, phosphinate, phosphonate, phosphonium, phosphorothioate, phosphoryl, sulfamoyl, sulfate, sulfinic acid, sulfonamido, sulfonate, sulfonic acid, sulfonyl, sulfoxido, thiol, thioureido, and ureido;
• R4 is selected from hydrogen, heteroalkyl, heteroaryl, and hydrocarbyl;
• and
• R5, R6, R7 and R8 at each occurrence is independently selected from heteroalkyl, heteroaryl, hydrocarbyl and hydrogen, with the proviso that R7 and R8 may join together to form a heterocyclic ring including the nitrogen to which they are both bonded.