This invention provides compounds, compositions and methods for treating Autism Spectrum Disorders (ASD) using glycyl-2-methylprolyl-glutamic acid (G-2-MePE) and analogs thereof. Autism Spectrum Disorders include Autism, Autistic Disorder Asperger Syndrome, Childhood Disintegrative Disorder, Pervasive Developmental Disorder—Not Otherwise Specified (PDD-NOS), Fragile X Syndrome, and Rett Syndrome. Compositions containing compounds include water-soluble formulations, water-in-oil micro-emulsions, water-in-oil coarse emulsions, water-in-oil liquid crystals, nanocapsules, tablets, and orally administered gels. The compounds and compositions of this invention can be administered intravenously, intraventricularly, parenterally, or orally, and can be effective in treating neurodegeneration, promoting neurological function, treating seizure activity and other symptoms of ASD, and can prolong life in animals including human beings having Autism Spectrum Disorders.
Oral formulations of G-2MePE including microemulsions, coarse emulsions, liquid crystals, tablets and encapsulated forms of G-2MePE have improved bioavailability than conventional aqueous formulations. In particular, microparticles, nanoparticles and microemulsions can exhibit great neuroprotective effects after oral administration. In a microemulsion formulation, G-2MePE can nearly completely inhibit cerebral infarction in an animal model of stroke even after the stroke had been initiated. Thus, improved oral formulations can be desirably used to treat a variety of neurodegenerative conditions with improved convenience and improved efficacy.
Embodiments of this invention provide methods for therapeutic use of cyclic G-2-Allyl Proline to treat cognitive disorders as well as manufacture of medicaments including tablets, capsules, injectable solutions that are useful for treatment of such conditions.
A61K 31/495 - Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two nitrogen atoms as the only ring hetero atoms, e.g. piperazine
C07D 241/36 - Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
C07D 471/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups
C07D 487/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups
A61K 31/4985 - Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
A61K 31/498 - Pyrazines or piperazines ortho- or peri-condensed with carbocyclic ring systems, e.g. quinoxaline, phenazine
4.
Oral formulations of glycyl-2-methylprolyl-glutamate
Oral formulations of G-2MePE including microemulsions, coarse emulsions, liquid crystals, tablets and encapsulated forms of G-2MePE have improved bioavailability than conventional aqueous formulations. In particular, microparticles, nanoparticles and microemulsions can exhibit great neuroprotective effects after oral administration. In a microemulsion formulation, G-2MePE can nearly completely inhibit cerebral infarction in an animal model of stroke even after the stroke had been initiated. Thus, improved oral formulations can be desirably used to treat a variety of neurodegenerative conditions with improved convenience and improved efficacy.
Embodiments of this invention provide methods for therapeutic use of cyclic G-2-allylProline (cG-2-allylP) to treat peripheral neuropathies, including toxin-induced peripheral neuropathy and diabetic peripheral neuropathy as well as manufacture of medicaments including tablets, capsules, and other orally active compositions containing cG-2-allylP, as well as injectable solutions that are useful for treatment of such conditions.
Embodiments of this invention provide novel peptidomimetics that contain a macrocycle, an embodiment of which is 2S,9′S,12′S)-2-{[(1′,4′-Diaza-2′-oxobicyclo[7.3.0]dodecyl)-12′-carbonyl]amino}-1,5-pentanedioic acid trifluoroacetate. Such compounds are neuroprotective and have utility as therapeutic agents for treatment of diseases, injuries and other conditions characterized by neuronal degeneration and/or neuronal cell death caused by in embodiments, toxicity or hypoxia. Compounds are also useful for manufacture of medicaments useful for treatment of such conditions.
C07D 487/02 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups in which the condensed system contains two hetero rings
C07D 491/02 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or in which the condensed system contains two hetero rings
C07D 495/02 - Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
C07D 497/02 - Heterocyclic compounds containing in the condensed system at least one hetero ring having oxygen and sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
7.
Oral formulations of glycyl-2-methylprolyl-glutamate
Oral formulations of G-2MePE including microemulsions, coarse emulsions, liquid crystals, tablets and encapsulated forms of G-2MePE have improved bioavailability than conventional aqueous formulations. In particular, microparticles, nanoparticles and microemulsions can exhibit great neuroprotective effects after oral administration. In a microemulsion formulation, G-2MePE can nearly completely inhibit cerebral infarction in an animal model of stroke even after the stroke had been initiated. Thus, improved oral formulations can be desirably used to treat a variety of neurodegenerative conditions with improved convenience and improved efficacy.
Embodiments of this invention provide novel cyclic compounds structurally related to diketopiperazines and methods for their therapeutic use. Such compounds are neuroprotective and have utility as therapeutic agents for treatment of diseases, injuries and other conditions characterized by neuronal degeneration and/or death. Compounds are also useful for manufacture of medicaments useful for treatment of such conditions.
A61K 31/517 - PyrimidinesHydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
9.
Cyclic G-2Allylproline in treatment of Parkinson's disease
Embodiments of this invention provide methods for thereapeutic use of cyclic G-2-Allyl Proline to treat disorders of dopaminergic neurons, including Parkinson's disease. Cyclic G-2Allyl P is neuroprotective and has utility as a therapeutic agent for treatment of diseases and other conditions characterised by degeneration and/or death of dopaminergic neurons and the adverse symptoms of such degeneration and/or death. Such symptoms include loss of cognition and motor function. Compounds are also useful for manufacture of medicaments including tablets, capsules and injectable solutions that are useful for treatment of such conditions.
A01N 43/42 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings condensed with carbocyclic rings
A01N 43/40 - Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
A61K 31/445 - Non-condensed piperidines, e.g. piperocaine
C07D 221/02 - Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups condensed with carbocyclic rings or ring systems
C07D 401/00 - Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
C07D 405/00 - Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
C07D 409/00 - Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
C07D 411/00 - Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen and sulfur atoms as the only ring hetero atoms
C07D 413/00 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
C07D 417/00 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group
C07D 419/00 - Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen, oxygen, and sulfur atoms as the only ring hetero atoms
C07D 421/00 - Heterocyclic compounds containing two or more hetero rings, at least one ring having selenium, tellurium, or halogen atoms as ring hetero atoms
Embodiments of this invention provide novel peptidomimetics that contain a macrocycle. Such compounds are neuroprotective and have utility as therapeutic agents for treatment of diseases, injuries and other conditions characterised by neuronal degeneration and/or death. Compounds are also useful for manufacture of medicaments useful for treatment of such conditions.
C07D 487/00 - Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups
C07D 491/00 - Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups , , or
C07D 513/00 - Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups , or
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