Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: 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.

Abstract: Certain embodiments of the invention provide a formulation suitable for nasal administration comprising water, a prodrug of a therapeutic agent, and an enzyme that is suitable for intranasal conversion of the prodrug to the therapeutic agent, as well as methods of use thereof.

Abstract: Certain embodiments of the invention provide a formulation suitable for nasal administration comprising water, a prodrug of a therapeutic agent, and an enzyme that is suitable for intranasal conversion of the prodrug to the therapeutic agent, as well as methods of use thereof.

Abstract: The invention provides compounds of formula I, II, III, or IV: wherein R1 to R11, X, and Y have any of the values defined in the specification. The compounds inhibit Na, K-ATPase ?4 and are useful as contraceptive agents.

Abstract: 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.

Abstract: The invention provides compounds of formula I, II, III, or IV: wherein R1 to R11, X, and Y have any of the values defined in the specification. The compounds inhibit Na, K-ATPase ?4 and are useful as contraceptive agents.

Abstract: Novel compounds useful for inhibiting spermatogenesis and cancer treatment, and in particular as inhibitors of heat shock proteins and/or elongation factor 1 alpha.

Abstract: Commercially feasible methods for synthesizing various epothilones precursors needed for the preparation of final epothilones are provided, including techniques for the synthesis of epothilone segment A and C precursors. Segment C precursors are prepared using starting nitriles, which can alternately be oxidized to ketones and converted, or reacted to form the diol with subsequent conversion to the segment. Segment A precursors are prepared by reacting a starting enone with a chiral catalyst to give an intermediate alcohol in high enantomeric excess, followed by conversion of the alcohol to the desired Segment A precursor.

Abstract: Commercially feasible methods for synthesizing various epothilones precursors needed for the preparation of final epothilones are provided, including techniques for the synthesis of epothilone segment C using a stereoselective Noyori-type reduction, and the coupling of epothilone segments B and C using an aldol condensation reaction. The synthesis methods may be used to prepare naturally occurring segments as well as a large number of related analogs and homologs thereof. Final epothilones in accordance with the invention may also be of the naturally occurring variety (16-membered macrolides), while the homologs and analogs thereof are preferably up to 20-membered macrolides.

Abstract: Commercially feasible methods for synthesizing various epothilones precursors needed for the preparation of final epothilones are provided, including techniques for the synthesis of epothilone segment A and C precursors. Segment C precursors are prepared using starting nitriles, which can alternately be oxidized to ketones and converted, or reacted to form the diol with subsequent conversion to the segment. Segment A precursors are prepared by reacting a starting enone with a chiral catalyst to give an intermediate alcohol in high enantomeric excess, followed by conversion of the alcohol to the desired Segment A precursor.

Abstract: Various epothilone precursors needed for the preparation of final epothilones are provided.

Abstract: Commercially feasible methods for synthesizing various epothilones precursors needed for the preparation of final epothilones are provided, including techniques for the synthesis of epothilone segment C using a stereoselective Noyori-type reduction, and the coupling of epothilone segments B and C using an aldol condensation reaction. The synthesis methods may be used to prepare naturally occurring segments as well as a large number of related analogs and homologs thereof. Final epothilones in accordance with the invention may also be of the naturally occurring variety (16-membered macrolides), while the homologs and analogs thereof are preferably up to 20-membered macrolides.

Abstract: An improved method for guanylating amines is provided. Broadly, the amines are reacted with a guanylating agent in the presence of a nickel catalyst. Preferably, the nickel catalyst comprises nickel in the zero oxidation state. Suitable nickel(0) catalysts are derived from nickel-boride alloys, nickel-phosphide alloys, aluminum-nickel alloys, nickel on kieselguhr, and nickel on silica/alumina catalysts. Preferred guanylating agents are thioureas and isothioureas. In one embodiment, protecting groups are selectively attached to the guanylating agents to yield particular substituted guanidines. The preferred protecting groups are Boc groups, Cbz groups, and arylsulfonyl groups. The reactions are particularly well suited for guanylating primary and secondary amines. The methods of the invention can be carried out under ambient conditions to provide high yields of the corresponding guanidines, with the nickel catalyst being essentially completely recoverable for reuse.