Abstract: Embodiments of the present invention provide solid oral dosage forms that upon daily administration to a subject provide plasma levels of decitabine with a 5-day AUC for decitabine that is equivalent to the 5-day AUC for a daily IV dose of decitabine of 20 mg/m2 administered as a one hour (1 h) infusion. Also provided according to embodiments of the present invention are solid oral dosage forms wherein upon daily administration to a subject provides a pharmacodynamic effect that is equivalent to the pharmacodynamic effect for a daily intravenous dose of decitabine of 20 mg/m2 administered as a one hour (1 h) infusion. Also provided are methods of treatment using a solid oral dosage form according to an embodiment of the invention.

Abstract: A method of synthesizing anhydrous lactic acid is provided by reacting a compound of formula (Ia): with an acid compound of formula HnX in a first solvent to produce a reaction mixture comprising a compound of formula (Ib) and a lactic acid compound of formula (I) in solution with the first solvent and/or water. n is an integer other than 0, x is 0, or an integer other than 0, M is an alkali metal or alkaline earth metal and X is the conjugate base of the acid compound of formula HnX. The resulting reaction mixture is filtered to produce a filtrate containing lactic acid in solution. The filtrate is crystalized from a second solvent to produce anhydrous lactic acid.

Abstract: The invention relates to methods of synthesizing 2?-deoxy-2?,2?-difluorotetrahydrouridine with increased purity and uniform particle size distribution. In particular, methods of the invention include crystallization and isolation procedures rendering synthetic reaction intermediates. The invention further includes compositions comprising the final compound in highly pure form, including lower number of impurities and lower levels of individual and total impurities.

Abstract: Embodiments of the present invention provide solid oral dosage forms that upon daily administration to a subject provide plasma levels of decitabine with a 5-day AUC for decitabine that is equivalent to the 5-day AUC for a daily IV dose of decitabine of 20 mg/m2 administered as a one hour (1 h) infusion. Also provided according to embodiments of the present invention are solid oral dosage forms wherein upon daily administration to a subject provides a pharmacodynamic effect that is equivalent to the pharmacodynamic effect for a daily intravenous dose of decitabine of 20 mg/m2 administered as a one hour (1 h) infusion. Also provided are methods of treatment using a solid oral dosage form according to an embodiment of the invention.

Abstract: A compound of formula (XXIII) and methods for preparation thereof are provided (XXIII).

Abstract: Embodiments of the present invention provide solid oral dosage forms that upon daily administration to a subject provide plasma levels of decitabine with a 5-day AUC for decitabine that is equivalent to the 5-day AUC for a daily IV dose of decitabine of 20 mg/m2 administered as a one hour (1 h) infusion. Also provided according to embodiments of the present invention are solid oral dosage forms wherein upon daily administration to a subject provides a pharmacodynamic effect that is equivalent to the pharmacodynamic effect for a daily intravenous dose of decitabine of 20 mg/m2 administered as a one hour (1 h) infusion. Also provided are methods of treatment using a solid oral dosage form according to an embodiment of the invention.

Abstract: The invention relates to methods of synthesizing 2?-deoxy-2?,2?-difluorotetrahydrouridine with increased purity and uniform particle size distribution. In particular, methods of the invention include crystallization and isolation procedures rendering synthetic reaction intermediates. The invention further includes compositions comprising the final compound in highly pure form, including lower number of impurities and lower levels of individual and total impurities.

Abstract: The present disclosure provides compounds and processes for the preparation of hypomethylating agents, including guadecitabine and salts thereof. The present disclosure also provides solid forms of guadecitabine sodium, including polymorphs that can exhibit decreased hygroscopicity and increased stability relative to other solid forms.

Abstract: The invention provides a method of preparing a lyophilized pharmaceutical composition containing a compound described herein or a pharmaceutically-acceptable salt thereof. The process comprises dissolving the compound in a solvent comprising dimethylsulfoxide and optionally one or more co-solvents to form a solution, and then removing the solvent and any co-solvents by a freeze-drying process. Also provided by the invention are lyophilized pharmaceutical compositions and their use in medicine and in particular in the treatment of cancer.

Abstract: The invention provides a method of preparing a lyophilized pharmaceutical composition containing a compound described herein or a pharmaceutically-acceptable salt thereof. The process comprises dissolving the compound in a solvent comprising dimethylsulfoxide and optionally one or more co-solvents to form a solution, and then removing the solvent and any co-solvents by a freeze-drying process. Also provided by the invention are lyophilized pharmaceutical compositions and their use in medicine and in particular in the treatment of cancer.

Abstract: The invention provides a method of preparing a lyophilized pharmaceutical composition containing a compound described herein or a pharmaceutically-acceptable salt thereof. The process comprises dissolving the compound in a solvent comprising dimethylsulfoxide and optionally one or more co-solvents to form a solution, and then removing the solvent and any co-solvents by a freeze-drying process. Also provided by the invention are lyophilized pharmaceutical compositions and their use in medicine and in particular in the treatment of cancer.

Abstract: The present invention provides a new method for making TH-302 and solid forms thereof. The compound in its solid form is an effective anti-cancer agent and may be used in various pharmaceutical compositions, and are particularly effective for the treatment of cancer. The invention also provides a method for preparing such compounds and forms and for treating cancer in a mammal comprising the step of administering a therapeutically effective amount of a solid form of TH-302 thereof.

Abstract: The invention provides a method of preparing a lyophilized pharmaceutical composition containing a compound described herein or a pharmaceutically-acceptable salt thereof. The process comprises dissolving the compound in a solvent comprising dimethylsulfoxide and optionally one or more co-solvents to form a solution, and then removing the solvent and any co-solvents by a freeze-drying process. Also provided by the invention are lyophilized pharmaceutical compositions and their use in medicine and in particular in the treatment of cancer.

Abstract: Compositions containing and methods of administering TH-4000 are useful in treatment of cancer alone or in combination with other anti-cancer agents.

Abstract: The present invention provides a new method for making TH-302 and solid forms thereof. The compound in its solid form is an effective anti-cancer agent and may be used in various pharmaceutical compositions, and are particularly effective for the treatment of cancer. The invention also provides a method for preparing such compounds and forms and for treating cancer in a mammal comprising the step of administering a therapeutically effective amount of a solid form of TH-302 thereof.

Abstract: The invention provides a method of preparing a lyophilized pharmaceutical composition containing a compound described herein or a pharmaceutically-acceptable salt thereof. The process comprises dissolving the compound in a solvent comprising dimethylsulfoxide and optionally one or more co-solvents to form a solution, and then removing the solvent and any co-solvents by a freeze-drying process. Also provided by the invention are lyophilized pharmaceutical compositions and their use in medicine and in particular in the treatment of cancer.

Abstract: The present invention provides a new method for making TH-302 and solid forms thereof. The compound in its solid form is an effective anti-cancer agent and may be used in various pharmaceutical compositions, and are particularly effective for the treatment of cancer. The invention also provides a method for preparing such compounds and forms and for treating cancer in a mammal comprising the step of administering a therapeutically effective amount of a solid form of TH-302 thereof.

Abstract: Compositions containing and methods of administering TH-4000 are useful in treatment of cancer alone or in combination with other anti-cancer agents.

Abstract: The present invention provides a new method for making TH-302 and solid forms thereof. The compound in its solid form is an effective anti-cancer agent and may be used in various pharmaceutical compositions, and are particularly effective for the treatment of cancer. The invention also provides a method for preparing such compounds and forms and for treating cancer in a mammal comprising the step of administering a therapeutically effective amount of a solid form of TH-302 thereof.

Abstract: Dosage forms and methods for providing a substantially ascending rate of release of paliperidone or risperidone are provided. The sustained release dosage forms provide therapeutically effective average steady-state plasma paliperidone or risperidone concentrations when administered once per day. This once-a-day dosing regimen results in only one peak plasma paliperidone or risperidone concentration occurrence in each 24 hour period. In addition, the peak plasma paliperidone or risperidone concentration occurs at a later time following dose administration and exhibits a lesser magnitude than the peak plasma paliperidone or risperidone concentration that occurs following administration of paliperidone or risperidone in an immediate-release dosage form.