C07D203/10

N-HETEROCYCLYL SUBSTITUTED 2-CYANO-3-(NAPHTHALEN-2-YL)ACRYLAMIDE DERIVATIVES AS FLUOROPHORS FOR DETECTION OF AMYLOID AND AMYLOID-LIKE PROTEINS FOR DIAGNOSIS OF NEURODEGENERATIVE DISORDERS
20240325572 · 2024-10-03 ·

Provided herein is the design and synthesis of novel molecular rotor fluorophores of formula I useful for detection of amyloid or amyloid like proteins. The fluorophores are designed to exhibit enhanced fluorescence emission upon associating with amyloid or amyloid like proteins as compared to unbound compound. Also disclosed herein are the compounds for use in methods for diagnosis and treatment of diseases associated with an amyloid or amyloid like proteins, such as e.g. Alzheimer's disease or traumatic brain injury (TBI), Parkinson's disease, vascular dementia, amyotrophic lateral sclerosis, Down syndrome, traumatic brain injury, chronic traumatic encephalopathy, schizophrenia or depression. Exemplary compounds are e.g. N-heterocyclyl substituted 2-cyano-3-(naphthalen-2-yl)acrylamide derivatives, such as e.g. (E)-2-cyano-N-(2-(2-hydroxy)ethoxy)ethyl)-3-(6-(pyrrolidin-1-yl)naphthalen-2-yl) acrylamide (example 1): Experimental data on in-vitro binding studies with amyloid beta is provided.

##STR00001##

N-HETEROCYCLYL SUBSTITUTED 2-CYANO-3-(NAPHTHALEN-2-YL)ACRYLAMIDE DERIVATIVES AS FLUOROPHORS FOR DETECTION OF AMYLOID AND AMYLOID-LIKE PROTEINS FOR DIAGNOSIS OF NEURODEGENERATIVE DISORDERS
20240325572 · 2024-10-03 ·

Provided herein is the design and synthesis of novel molecular rotor fluorophores of formula I useful for detection of amyloid or amyloid like proteins. The fluorophores are designed to exhibit enhanced fluorescence emission upon associating with amyloid or amyloid like proteins as compared to unbound compound. Also disclosed herein are the compounds for use in methods for diagnosis and treatment of diseases associated with an amyloid or amyloid like proteins, such as e.g. Alzheimer's disease or traumatic brain injury (TBI), Parkinson's disease, vascular dementia, amyotrophic lateral sclerosis, Down syndrome, traumatic brain injury, chronic traumatic encephalopathy, schizophrenia or depression. Exemplary compounds are e.g. N-heterocyclyl substituted 2-cyano-3-(naphthalen-2-yl)acrylamide derivatives, such as e.g. (E)-2-cyano-N-(2-(2-hydroxy)ethoxy)ethyl)-3-(6-(pyrrolidin-1-yl)naphthalen-2-yl) acrylamide (example 1): Experimental data on in-vitro binding studies with amyloid beta is provided.

##STR00001##

KYNURENINE-3-MONOOXYGENASE INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF

Certain compounds, or pharmaceutically acceptable salts or prodrugs thereof, are provided herein. Also provided are pharmaceutical compositions comprising at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein as a single active agent or administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

KYNURENINE-3-MONOOXYGENASE INHIBITORS, PHARMACEUTICAL COMPOSITIONS, AND METHODS OF USE THEREOF

Certain compounds, or pharmaceutically acceptable salts or prodrugs thereof, are provided herein. Also provided are pharmaceutical compositions comprising at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein and one or more pharmaceutically acceptable vehicle. Methods of treating patients suffering from certain diseases and disorders responsive to the inhibition of KMO activity are described, which comprise administering to such patients an amount of at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein effective to reduce signs or symptoms of the disease or disorder are disclosed. These diseases include neurodegenerative disorders such as Huntington's disease. Also described are methods of treatment include administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein as a single active agent or administering at least one compound, or pharmaceutically acceptable salt or prodrug thereof, described herein in combination with one or more other therapeutic agents. Also provided are methods for screening compounds capable of inhibiting KMO activity.

Cardanol glycidyl ether derivatives

Methacrylated cardanol glycidyl ethers, diglycidyl ethers, intermediates and derivatives thereof are described herein. Compositions and polymers made with such compounds as well as methods of preparation thereof are also described. For example, compounds of Formulas: wherein n, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 can each represent various different entities are described in the present disclosure.

Cardanol glycidyl ether derivatives

Methacrylated cardanol glycidyl ethers, diglycidyl ethers, intermediates and derivatives thereof are described herein. Compositions and polymers made with such compounds as well as methods of preparation thereof are also described. For example, compounds of Formulas: wherein n, R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, and R.sub.6 can each represent various different entities are described in the present disclosure.

NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structures:

##STR00001##

NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention provides lipids having the following structures:

##STR00001##

NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention

##STR00001##

provides lipids having the following structure XXXIII, wherein:
R.sub.1 and R.sub.2 are each independently for each occurrence optionally substituted C.sub.10-C.sub.30 alkyl, optionally substituted C.sub.10-C.sub.30 alkenyl, optionally substituted C.sub.10-C.sub.30 alkynyl, optionally substituted C.sub.10-C.sub.30 acyl, or -linker-ligand; R.sub.3 is H, optionally substituted C.sub.1-C.sub.10 alkyl, optionally substituted C.sub.2-C.sub.10 alkenyl, optionally substituted C.sub.2-C.sub.10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, -aminoalkyls, -(substituted)aminoalkyls, -phosphoalkyls, -thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).

NOVEL LIPIDS AND COMPOSITIONS FOR THE DELIVERY OF THERAPEUTICS

The present invention provides lipids that are advantageously used in lipid particles for the in vivo delivery of therapeutic agents to cells. In particular, the invention

##STR00001##

provides lipids having the following structure XXXIII, wherein:
R.sub.1 and R.sub.2 are each independently for each occurrence optionally substituted C.sub.10-C.sub.30 alkyl, optionally substituted C.sub.10-C.sub.30 alkenyl, optionally substituted C.sub.10-C.sub.30 alkynyl, optionally substituted C.sub.10-C.sub.30 acyl, or -linker-ligand; R.sub.3 is H, optionally substituted C.sub.1-C.sub.10 alkyl, optionally substituted C.sub.2-C.sub.10 alkenyl, optionally substituted C.sub.2-C.sub.10 alkynyl, alkylhetrocycle, alkylphosphate, alkylphosphorothioate, alkylphosphorodithioate, alkylphosphonates, alkylamines, hydroxyalkyls, -aminoalkyls, -(substituted)aminoalkyls, -phosphoalkyls, -thiophosphoalkyls, optionally substituted polyethylene glycol (PEG, mw 100-40K), optionally substituted mPEG (mw 120-40K), heteroaryl, heterocycle, or linker-ligand; and E is C(O)O or OC(O).