Methods and compositions for stimulating neurogenesis and inhibiting neuronal degeneration
Inventors
Assignees
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Publication Number
US-9539261-B2
Publication Date
2017-01-10
Expiration Date
Abstract
The present invention provides methods and compositions comprising compounds useful for stimulating neurogenesis. The methods and compositions comprising compounds are also useful for inhibiting neuronal degeneration. Thus, the present invention can be used in the treatment of diseases and conditions characterized by neuronal loss and reduced neurogenesis including Alzheimer's disease, stroke, traumatic brain injury, and depression. This invention could also be used for research products including single agents or mixtures of agents to promote, proliferate, differentiate, or maintain neurons from stem or progenitor cells.
Core Innovation
The invention relates to a method for stimulating neurogenesis and/or inhibiting neuronal degeneration in a human patient suffering from a condition selected from Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis (ALS), post-traumatic stress disorder, depression, cognitive impairment, dementia, anxiety, mood disorders, bipolar disorder, and psychiatric disorders. The method includes administering to the human patient a pharmaceutical composition comprising a compound of the formula, with variable substituents R1, R2, R3, R4, R5, R6, and related R7 definitions, and a pharmaceutically acceptable carrier in an amount effective to stimulate neurogenesis and/or inhibit neuronal degeneration in the human patient.
The chemical scaffold is provided using formula-based variable substituents, in which substituents such as R1 through R7 are defined with groups including halo, substituted alkyl, substituted aryl, substituted aralkyl, O-R7, cyclic and substituted moieties, and substituted heterocyclic aromatic groups. The partial content also describes specific example compounds within these scaffold families, including quinolinyl, diazepane, piperidine, piperazine, thiourea, and carbothioic acid amides, as members associated with the described formula-based compound structures.
The disclosed approach further includes pharmaceutical composition and administration concepts, where the effective amount is delivered to a mammal or human, and the composition includes pharmaceutically acceptable carriers and formulation components such as salts, excipients, and optional liposomes. Routes of administration described include oral and parenteral routes, and the method is framed to deliver an amount effective to stimulate neurogenesis and/or inhibit neuronal degeneration, including administration as a daily dosage using regimen options that include single daily dosing and divided daily dosing.
Claims Coverage
The independent claims are clm-00001, clm-00002, and clm-00003. Across these independent claims, the coverage centers on administering an amount-effective pharmaceutical composition containing a formula-defined compound with variable substituents, to stimulate neurogenesis and/or inhibit neuronal degeneration in a human patient suffering from selected neurological/psychiatric conditions, using a pharmaceutically acceptable carrier.
Stimulating neurogenesis or inhibiting neuronal degeneration with formula-defined compounds
A method for stimulating neurogenesis and/or inhibiting neuronal degeneration in a human patient suffering from a condition selected from Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis (ALS), post-traumatic stress disorder, depression, cognitive impairment, dementia, anxiety, mood disorders, bipolar disorder, and psychiatric disorders comprising administering a pharmaceutical composition comprising a compound of the formula with defined substituents R1, R2, R3, R4, R5, and R6 and a pharmaceutically acceptable carrier in an amount effective to stimulate neurogenesis and/or inhibit neuronal degeneration.
Stimulating neurogenesis or inhibiting neuronal degeneration with broader R3/R2 substitution definitions
A method for stimulating neurogenesis and/or inhibiting neuronal degeneration in a human patient suffering from a condition selected from Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis (ALS), post-traumatic stress disorder, depression, cognitive impairment, dementia, anxiety, mood disorders, bipolar disorder, and psychiatric disorders comprising administering a pharmaceutical composition in an amount effective to stimulate neurogenesis and/or inhibit neuronal degeneration in the human patient, said pharmaceutical composition comprising a compound with R1 and R7 selection, R2 selected from O or S, and R3 selected from alkyl, cyclic alkyl, aralkyl of 1-10 carbons, a substituted aromatic group, or a substituted heteroaromatic group, and a pharmaceutically acceptable carrier.
Stimulating neurogenesis or inhibiting neuronal degeneration with expanded R3/R4 substituent options
A method for stimulating neurogenesis and/or inhibiting neuronal degeneration in a human patient suffering from a condition selected from Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis (ALS), post-traumatic stress disorder, depression, cognitive impairment, dementia, anxiety, mood disorders, bipolar disorder, and psychiatric disorders comprising administering a pharmaceutical composition in an amount effective to stimulate neurogenesis and/or inhibit neuronal degeneration in the human patient, said pharmaceutical composition comprising a compound with R1 and R7 selection, R2 selected from O or S, R3 selected from a 1-6 carbon alkyl or an ether of 1-6 carbons, and R4 selected from specified substituted aryl/aralkyl/aromatic/heteroaromatic options including specified substituted heteroaromatic-alkyl alternatives, and a pharmaceutically-acceptable carrier.
Across the independent claims, the inventive coverage is directed to methods that administer an amount-effective pharmaceutical composition containing a compound defined by formula-based variable substituents (R1/R2/R3/R4/R5/R6 and related R7 definitions) together with a pharmaceutically acceptable carrier, for stimulating neurogenesis and/or inhibiting neuronal degeneration in a human patient with one of the listed neurological/psychiatric conditions.
Stated Advantages
Stimulating neurogenesis.
Inhibiting neuronal degeneration.
Documented Applications
Treating human patients suffering from conditions selected from Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, traumatic brain injury, stroke, amyotrophic lateral sclerosis (ALS), post-traumatic stress disorder, depression, cognitive impairment, dementia, anxiety, mood disorders, bipolar disorder, and psychiatric disorders by administering a pharmaceutical composition that is effective to stimulate neurogenesis and/or inhibit neuronal degeneration.
Parenteral administration of the pharmaceutical composition in sterile injectable solutions or suspensions, isotonic preparations, and lyophilized (freeze-dried) presentations, including unit-dose or multi-dose containers.
Use of prolonged or sustained-release delivery systems such as depots/implants, microparticles, and polymer matrices for administration of the pharmaceutical composition.
Research applications are described in the partial content as use cases for the neurogenic/anti-neurodegenerative compounds and pharmaceutical compositions.
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