Heterocyclic anti-epileptogenic agents and methods of use thereof
AssigneeQueen's University at Kingston
InventorsDonald F. Weaver, Allyson J. Campbell
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Abstract
Methods and compounds, such as β-heterocyclic-β-amino acids, useful for the inhibition of epileptogenesis are disclosed. Methods for preparing and using the β-heterocyclic-β-amino acids of the invention are also described.
Claims42
A method for inhibiting epileptogenesis in a subject, comprising administering to said subject an effective amount of an anti-epileptogenic agent, such that said epileptogenesis in said subject is inhibited, wherein said anti-epileptogenic agent is a β-heterocyclic-β-amino acid, or a salt or ester, N-substituted analog, C-substituted analog, bioisostere, or prodrug thereof.
A method for treating a subject suffering from an epileptogenesis-associated condition, comprising administering to said subject an effective amount of an anti-epileptogenic agent, such that said subject is treated wherein said anti-epileptogenic agent is a β-heterocyclic-β-amino acid, or a salt or ester, N-substituted analog, C-substituted analog, bioisostere, or prodrug thereof.
A method for treating convulsions in a subject comprising administering to said subject an effective amount of an anti-epileptogenic agent, such that said subject is treated, wherein said anti-epileptogenic agent is a β-heterocyclic-β-amino acid, or a salt or ester, N-substituted analog, C-substituted analog, bioisostere, or prodrug thereof.
A method for inhibiting epileptogenesis in a subject, comprising administering to said subject an effective amount of an anti-epileptogenic agent such that said epileptogenesis is inhibited, wherein said anti-epileptogenic agent is of the Formula:
- 55
- wherein:
- X is a heterocyclic moiety;
- E is a hydrogen bond donor;
- Y is a connecting moiety;
- A is an hydrogen bond acceptor,
- and pharmaceutically acceptable salts or esters, N-substituted analogs, C-substituted analogs, bioisosteres, and prodrugs thereof.
A method for treating a epileptogenesis-associated condition in a subject, comprising administering to said subject an effective amount of an anti-epileptogenic agent such that said subject is treated for said epileptogenesis-associated condition, wherein said anti-epileptogenic agent is of the Formula:
- 56
- wherein
- X is a heterocyclic moiety;
- Y is a connecting moiety;
- E is a hydrogen bond donor;
- A is an hydrogen bond acceptor,
- and pharmaceutically acceptable salts or esters, N-substituted analogs, C-substituted analogs, bioisosteres, and prodrugs thereof.
A method for treating convulsions in a subject, comprising administering to said subject an effective amount of an anti-epileptogenic agent such that said subject is treated for said convulsions, wherein said anti-epileptogenic agent is of the Formula:
- 57
- wherein
- X is a heterocyclic moiety;
- Y is a connecting moiety;
- E is a hydrogen bond donor;
- A is an hydrogen bond acceptor,
- and pharmaceutically acceptable salts or esters, N-substituted analogs, C-substituted analogs, bioisosteres, and prodrugs thereof.
A pharmaceutical composition, comprising a therapeutically effective amount of an anti-epileptogenic agent and a pharmaceutical acceptable carrier, wherein said anti-epileptogenic agent is of the Formula:
- 59
- wherein:
- X is a heterocyclic moiety;
- E is a hydrogen bond donor;
- A is an hydrogen bond acceptor,
- and pharmaceutically acceptable salts or esters, N-substituted analogs, C-substituted analogs, bioisosteres, and prodrugs thereof.
A pharmaceutical composition, comprising a therapeutically effective amount of an anti-epileptogenic agent and a pharmaceutical acceptable carrier, wherein said anti-epileptogenic agent is selected from the group consisting of those compounds illustrated in the accompanying Examples and Tables herein.
A compound selected from the group consisting of those compounds illustrated in the accompanying Examples and Tables.
A method of diagnosing an epileptogenesis-associated condition in a subject comprising administering an anti-epileptogenic agent, labeled with a detectable marker to said subject;
- and measuring increased binding of the compound to the NMDA receptors of the neurons of said subject's brain, thereby diagnosing an epileptogenesis-associated condition in said subject, wherein said anti-epileptogenic agent is a β-heterocyclic-β-amino acid or a compound of the Formula:
- 60
- wherein
- X is a heterocyclic moiety;
- Y is a connecting moiety;
- E is a hydrogen bond donor;
- A is an hydrogen bond acceptor,
- and pharmaceutically acceptable salts or esters, N-substituted analogs, C-substituted analogs, bioisosteres, and prodrugs thereof.
A method of diagnosing an epileptogenesis-associated state, comprising administering an anti-epileptogenic agent labeled with a detectable marker to a subject;
- and measuring decreased binding of the compound to the GABA receptors or transporters of the neurons of said subject's brain, thereby diagnosing the epileptogenesis-associated condition in said subject, wherein said anti-epileptogenic agent is a β-heterocyclic-β-amino acid or a compound of the Formula:
- 61
- wherein
- X is a heterocyclic moiety;
- Y is a connecting moiety;
- E is a hydrogen bond donor;
- A is an hydrogen bond acceptor,
- and pharmaceutically acceptable salts or esters, N-substituted analogs, C-substituted analogs, bioisosteres, and prodrugs thereof.
A method for inhibiting epileptogenesis in a subject, comprising administering to said subject an effective amount of an anti-epileptogenic agent, such that said epileptogenesis in said subject is inhibited, wherein said anti-epileptogenic agent is of the Formula (IIa):
- 62
- wherein:
- R2 and R3 are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylaryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl;
- X is a heterocyclic moiety;
- and
- R* is a substituted or unsubstituted alkyl moiety, a substituted or unsubstituted aryl moiety, a hydrogen, or a physiologically acceptable cation;
- and pharmaceutically acceptable salts, bioisosteres, and prodrugs thereof.
A method for treating a subject suffering from an epileptogenesis-associated disorder, comprising administering to said subject an effective amount of an anti-epileptogenic agent, such that said subject is treated wherein said anti-epileptogenic agent is of the Formula (IIa):
- 63
- wherein:
- R2 and R3 are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylaryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl;
- X is a heterocyclic moiety;
- and
- R* is a substituted or unsubstituted alkyl moiety, a substituted or unsubstituted aryl moiety, a hydrogen, or a physiologically acceptable cation;
- and pharmaceutically acceptable salts, bioisosteres, and prodrugs thereof.
A method for treating convulsions in a subject comprising administering to said subject an effective amount of an anti-epileptogenic agent, such that said subject is treated, wherein said anti-epileptogenic agent is of the Formula (IIa):
- 64
- wherein:
- R2 and R3 are each independently hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, alkylaryl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl;
- X is a heterocyclic moiety;
- and
- R* is a substituted or unsubstituted alkyl moiety, a substituted or unsubstituted aryl moiety, a hydrogen, or a physiologically acceptable cation;
- and pharmaceutically acceptable salts, bioisosteres, and prodrugs thereof.
Dependencies are inferred from the claim text.