The present invention provides benzothiadiazine and chroman derivatives and particularly diazoxide and cromakalim derivatives for use in treating glaucoma, retinopathy, treating age related macular degeneration, treating, stabilizing and/or inhibiting blood and lymph vascularization, and reducing intraocular pressure by administering a pharmaceutically effective amount of a prodrug disposed in an ophthalmically acceptable carrier to the eye, wherein the prodrug specifically modulates a KATP channel to reduce an intraocular pressure.

The present invention provides benzothiadiazine and chroman derivatives and particularly diazoxide and cromakalim derivatives for use in treating glaucoma, retinopathy, treating age related macular degeneration, treating, stabilizing and/or inhibiting blood and lymph vascularization, and reducing intraocular pressure by administering a pharmaceutically effective amount of a prodrug disposed in an ophthalmically acceptable carrier to the eye, wherein the prodrug specifically modulates a K.sub.ATP channel to reduce an intraocular pressure.

The present invention provides benzothiadiazine and chroman derivatives and particularly diazoxide and cromakalim derivatives for use in treating glaucoma, retinopathy, treating age related macular degeneration, treating, stabilizing and/or inhibiting blood and lymph vascularization, and reducing intraocular pressure by administering a pharmaceutically effective amount of a prodrug disposed in an ophthalmically acceptable carrier to the eye, wherein the prodrug specifically modulates a K.sub.ATP channel to reduce an intraocular pressure.

Provided are immediate or prolonged administration of certain salts of K.sub.ATP channel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving K.sub.ATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals.

Provided are immediate or prolonged administration of certain salts of K.sub.ATP channel openers such as diazoxide to a subject to achieve novel pharmacodynamic, pharmacokinetic, therapeutic, physiological, metabolic and compositional outcomes in the treatment of diseases or conditions involving K.sub.ATP channels. Also provided are pharmaceutical formulations, methods of administration and dosing of the salts that achieve these outcomes and reduce the incidence of adverse effects in treated individuals. Further provided are method of co-administering the salts with other drugs to treat diseases of humans and animals.

A method for preparing diazoxide includes reacting o-aminobenzenesulfonamide with N-chlorosuccinimide in a chlorine solvent to obtain 2-amino-5-chlorobenzenesulfonamide, mixing the 2-amino-5-chlorobenzenesulfonamide, an imidazole salt and an amide solvent, then heating same for reaction so as to obtain diazoxide; or mixing o-aminobenzenesulfonamide, an imidazole salt and an amide solvent, then heating same for reaction to obtain a compound IV; then reacting the compound IV with N-chlorosuccinimide in a chlorine solvent to obtain diazoxide. The application of imidazole hydrochloride as a catalyst in preparing diazoxide is also disclosed. The present invention avoids the use of highly corrosive and toxic chlorosulfonyl isocyanate, a strong acid (sulfuric acid), and a high reaction temperature (240-250? C.), and the reaction steps are short; the total yield of the two steps is more than 90%, and compared with publicly disclosed preparation methods for diazoxide, the synthesis route overcomes numerous shortcomings, thus being more suitable for industrial production.

A method for preparing diazoxide includes reacting o-aminobenzenesulfonamide with N-chlorosuccinimide in a chlorine solvent to obtain 2-amino-5-chlorobenzenesulfonamide, mixing the 2-amino-5-chlorobenzenesulfonamide, an imidazole salt and an amide solvent, then heating same for reaction so as to obtain diazoxide; or mixing o-aminobenzenesulfonamide, an imidazole salt and an amide solvent, then heating same for reaction to obtain a compound IV; then reacting the compound IV with N-chlorosuccinimide in a chlorine solvent to obtain diazoxide. The application of imidazole hydrochloride as a catalyst in preparing diazoxide is also disclosed. The present invention avoids the use of highly corrosive and toxic chlorosulfonyl isocyanate, a strong acid (sulfuric acid), and a high reaction temperature (240-250? C.), and the reaction steps are short; the total yield of the two steps is more than 90%, and compared with publicly disclosed preparation methods for diazoxide, the synthesis route overcomes numerous shortcomings, thus being more suitable for industrial production.

The invention is directed towards compounds, methods of stimulating myelination, stimulating proliferation of oligodendrocytes (OLs) or stimulating oligodendrocyte precursor cells and methods of treating diseases, disorders or symptoms thereof.

The invention is directed towards compounds, methods of stimulating myelination, stimulating proliferation of oligodendrocytes (OLs) or stimulating oligodendrocyte precursor cells and methods of treating diseases, disorders or symptoms thereof.

The disclosures herein relate to novel compounds of formula wherein W, X and Y.sub.1, Y.sub.2, Y.sub.3 and Y.sub.4 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of neurological or psychiatric disorders associated with orexin receptors. ##STR00001##