Abstract: In alternative embodiments, provided are uncharged bis-oxime antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). In alternative embodiments, provided are pumps, devices, subcutaneous infusion devices, continuous subcutaneous infusion devices, infusion pens, needles, reservoirs, ampoules, a vial, a syringe, a cartridge, a disposable pen or jet injector, a prefilled pen or a syringe or a cartridge, a cartridge or a disposable pen or jet injector, a two chambered or multi-chambered pump, a syringe, a cartridge or a pen or a jet injector, comprising a compound as provided herein.

Abstract: Provided are nitrile- and alkyne-substituted {1,2,4,} triazolo {1,5-A} pyrimidine compounds, compositions containing such compounds, and methods for treating a neurodegenerative disease or cancer by administration of such compounds.

Abstract: The present disclosure provides compounds of formula (I) or (II) or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Rx-R8 are defined herein. Also provided are compositions comprising a compound described herein and a pharmaceutically effective excipient, methods of stabilizing microtubules in a patient comprising administering to the patient a microtubule-stabilizing amount of a compound described herein, methods of treating cancer in a patient comprising administering to the patient a therapeutically effective amount of a compound described herein, and methods of treating a neurodegenerative disease in a patient comprising administering to the patient a therapeutically effective amount of a compound described herein.

Abstract: Compositions and methods for treating thrombosis, inflammation, and atherosclerosis by administration of a compound that binds to KRIT1 to inhibit binding with HEG1.

Abstract: The present disclosure provides compounds of formula (I) or a pharmaceutically acceptable salt or stereoisomer thereof, wherein R1-R6 are defined herein. Also provided are compositions comprising a compound described herein and a pharmaceutically effective excipient, methods of stabilizing microtubules in a patient comprising administering to the patient a microtubule-stabilizing amount of a compound described herein, methods of treating cancer in a patient comprising administering to the patient a therapeutically effective amount of a compound described herein, and methods of treating a neurodegenerative disease in a patient comprising administering to the patient a therapeutically effective amount of a compound described herein.

Abstract: In alternative embodiments, provided are uncharged bis-oxime antidotes that cross the blood-brain barrier (BBB) to catalyze the hydrolysis of organophosphate (OP)-inhibited human acetylcholinesterase (hAChE) in the central nerve system (CNS). In alternative embodiments, provided are pumps, devices, subcutaneous infusion devices, continuous subcutaneous infusion devices, infusion pens, needles, reservoirs, ampoules, a vial, a syringe, a cartridge, a disposable pen or jet injector, a prefilled pen or a syringe or a cartridge, a cartridge or a disposable pen or jet injector, a two chambered or multi-chambered pump, a syringe, a cartridge or a pen or a jet injector, comprising a compound as provided herein.

Abstract: The disclosure provides for new substituted cysteamine and cystamine compounds, pharmaceutical compositions made thereof, and methods thereof including the treatment of any disease or disorder in a subject that can benefit from one or more of the bioprotective effects of the compounds, including but not limited to, binding of cystine, reducing oxidative stress, increasing adiponectin levels and/or increasing brain-derived neurotrophic factors. Examples of such disease and disorders, include but are not limited to, cystinosis, and fatty liver diseases.

Abstract: The present disclosure provides compounds of formula (I) or (II) or a pharmaceutically acceptable salt or stereoisomer thereof, wherein Rx-R8 are defined herein. Also provided are compositions comprising a compound described herein and a pharmaceutically effective excipient, methods of stabilizing microtubules in a patient comprising administering to the patient a microtubule-stabilizing amount of a compound described herein, methods of treating cancer in a patient comprising administering to the patient a therapeutically effective amount of a compound described herein, and methods of treating a neurodegenerative disease in a patient comprising administering to the patient a therapeutically effective amount of a compound described herein.

Abstract: The present invention is directed to triazolopyrimidine, phenylpyrimidine, pyridopyridazine, and pyridotriazine compounds and their use in the treatment of neurodegenerative disorders.

Abstract: The present invention is directed to triazolopyrimidine, phenylpyrimidine, pyridopyridazine, and pyridotriazine compounds which are microtubule-stabilizing compounds and their use in the treatment of neurodegenerative disorders, in particular, tauopathies, such as for example, Alzheimer's disease, frontotemporal lobar degeneration, Pick's disease, progressive supranuclear palsy (PSP), and corticobasal degeneration. In addition, the compounds of the invention may be useful for other diseases where tau pathology is a comorbidity or where microtubule function is compromised, for example, schizophrenia, Parkinson's disease (PD), PD with dementia, Lewy body disease with dementia, and amyotrophic lateral sclerosis.

Abstract: The present invention is directed to compounds of formula I: wherein A is n is 0, 1, or 2; m is 0 or 1; R1 is H or C1-6alkyl and R2 is H, C1-6alkyl, C1-6alkaryl, aryl, or heteroaryl; and X is O or NH. Tautomers, enantiomers, and diastereomers, as well as pharmaceutically acceptable salt forms, of compounds of formula I are also within the scope of the invention. Methods of preparing and using the compounds of formula I are also described.

Abstract: The present invention is directed to compounds of formula I: wherein A is n is 0, 1, or 2; m is 0 or 1; R1 is H or C1-6alkyl and R2 is H, C1-6alkyl, C1-6alkaryl, aryl, or heteroaryl; and X is O or NH. Tautomers, enantiomers, and diastereomers, as well as pharmaceutically acceptable salt forms, of compounds of formula I are also within the scope of the invention. Methods of preparing and using the compounds of formula I are also described.

Abstract: The present invention is directed to triazolopyrimidine, phenylpyrimidine, pyridopyridazine, and pyridotriazine compounds which are microtubule-stabilizing compounds and their use in the treatment of neurodegenerative disorders, in particular, tauopathies, such as for example, Alzheimer's disease, frontotemporal lobar degeneration, Pick's disease, progressive supranuclear palsy (PSP), and corticobasal degeneration. In addition, the compounds of the invention may be useful for other diseases where tau pathology is a comorbidity or where microtubule function is compromised, for example, schizophrenia, Parkinson's disease (PD), PD with dementia, Lewy body disease with dementia, and amyotrophic lateral sclerosis.

Abstract: The present invention relates to novel TP receptor antagonists, which optionally cross the blood-brain barrier of a mammal. The invention also provides methods for treating a disorder related to activation of TP receptor utilizing the compounds of the invention.

Abstract: The present invention is directed to carboxylic acid-containing pharmaceutical compounds where the carboxylic acid moieties have been substituted with cycloalkyl-dione derivatives, as well as tautomers and pharmaceutically acceptable salt forms thereof. These bioisosteric replacements improve the compound's ability to effectively cross the blood brain barrier and result in improved pharmacokinetic, toxicological, and/or safety profiles.

Abstract: The present invention relates to TP receptor antagonists, which have the ability to bind to TP receptor and optionally cross the blood brain barrier. The invention also provides compositions and methods for treating a disorder wherein activation of TP receptor is detrimental.

Abstract: The present invention is directed to methods of inhibiting a tauopathy in a patient by administration of a compound of formula I: Novel aminothienopyridazine compounds are also described.

Abstract: The present invention is directed to compounds of formula I: wherein A is n is 0, 1, or 2; m is 0 or 1; R1 is H or C1-6alkyl and R2 is H, C1-6 alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; and X is O or N; as well as tautomers and pharmaceutically acceptable salt forms thereof. Uses of these compounds are also described.

Abstract: Provided herein are C-10 taxane carbamates and pharmaceutically acceptable derivatives thereof. In certain embodiments, provided herein are compounds, compositions and methods for treating cancer and taupathy.

Abstract: Provided herein are C-10 taxane carbamates and pharmaceutically acceptable derivatives thereof. In certain embodiments, provided herein are compounds, compositions and methods for treating cancer and taupathy.