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: The present disclosure provides in one aspect monoclonal antibodies that bind ?-Synuclein. In certain aspects, the antibodies preferentially bind to ?-Synuclein fibrils over ?-Synuclein monomer. In other aspects, the disclosure provides a method of treating, ameliorating, and/or preventing ?-Synucleopathic disease in a subject, comprising administering any one of the antibodies of the disclosure to the subject. In yet other aspects, the disclosure provides methods of detecting ?-Synuclein fibrils using any one of the antibodies of the disclosure.

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: The present disclosure provides monoclonal antibodies that bind ?-Synuclein. In certain aspects, the antibodies preferentially bind to ?-Synuclein fibrils over ?-Synuclein monomer. In other aspects, the invention comprises a method of treating ?-Synucleopathic disease in a subject, comprising administering any of the antibodies of the invention to the subject. In yet other aspects, the invention comprises methods of detecting ?-Synuclein fibrils using any of the antibodies of the invention.

Abstract: The present disclosure provides monoclonal antibodies that bind ?-Synuclein. In certain aspects, the antibodies preferentially bind to ?-Synuclein fibrils over ?-Synuclein monomer. In other aspects, the invention comprises a method of treating ?-Synucleopathic disease in a subject, comprising administering any of the antibodies of the invention to the subject. In yet other aspects, the invention comprises methods of detecting ?-Synuclein fibrils using any of the antibodies of the invention.

Abstract: The present disclosure provides monoclonal antibodies that bind ?-Synuclein. In certain aspects, the antibodies preferentially bind to ?-Synuclein fibrils over ?-Synuclein monomer. In other aspects, the invention comprises a method of treating ?-Synucleopathic disease in a subject, comprising administering any of the antibodies of the invention to the subject. In yet other aspects, the invention comprises methods of detecting ?-Synuclein fibrils using any of the antibodies of the invention.

Abstract: The present disclosure provides monoclonal antibodies that bind ?-Synuclein. In certain aspects, the antibodies preferentially bind to ?-Synuclein fibrils over ?-Synuclein monomer. In other aspects, the invention comprises a method of treating ?-Synucleopathic disease in a subject, comprising administering any of the antibodies of the invention to the subject. In yet other aspects, the invention comprises methods of detecting ?-Synuclein fibrils using any of the antibodies of the invention.

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 disclosure provides monoclonal antibodies that bind ?-Synuclein. In certain aspects, the antibodies preferentially bind to ?-Synuclein fibrils over ?-Synuclein monomer. In other aspects, the invention comprises a method of treating ?-Synucleopathic disease in a subject, comprising administering any of the antibodies of the invention to the subject. In yet other aspects, the invention comprises methods of detecting ?-Synuclein fibrils using any of the antibodies of the invention.

Abstract: The present disclosure provides monoclonal antibodies that bind ?-Synuclein. In certain aspects, the antibodies preferentially bind to ?-Synuclein fibrils over ?-Synuclein monomer. In other aspects, the invention comprises a method of treating ?-Synucleopathic disease in a subject, comprising administering any of the antibodies of the invention to the subject. In yet other aspects, the invention comprises methods of detecting ?-Synuclein fibrils using any of the antibodies of the invention.

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 relates to a cell-based model useful for identifying molecules that modify intracellular pathways of ?-synuclein and tau aggregation and degradation.

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.