2, 6-disubstituted piperidines as modulators of nicotinic acetylcholine receptor mediated neurotransmitter release, uptake and storage
AssigneeUniversity of Kentucky Research Foundation
InventorsPeter A. Crooks, Linda Dwoskin, Dennis Keith Miller, Vladimir P. Grinevich, Seth Davin Norrholm, Guangrong Zheng
Life of this patent
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Abstract
Compounds used for treating dependence on or withdrawal from a drug of abuse, for an eating disorder or for a CNS disease or pathology having the following formulas: 1
Claims20
A method of treating an individual for dependence on or withdrawal from a drug of abuse, for an eating disorder or for a CNS disease or pathology, comprising the step of administering to the individual an effective amount of a 2,6-substituted piperidino compound and pharmaceutically effective salts thereof, including resolved diasteriomers, enantiomers thereof, comprising formula (I):
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- wherein:
- R1 represents a hydrogen, methyl, deuteromethyl (CD3), tritiomethyl (CT3), ethyl, or C3-C7 straight chain or branched alkyl, C3-C6 cycloalkyl, vinyl, allyl, C4-C7 alkenyl, benzyl, and phenylethyl;
- R2 and R3 are each independently ortho-, meta-, or para-substituted moieties, where the substituted moiety is selected from the group consisting of hydrogen, methyl, ethyl, C3-C7 straight chain or branched alkyl, C3-C6 cycloalkyl, vinyl, allyl, C4-C7 alkenyl, benzyl, phenylethyl, N-methylamino, N,N-dimethylamino, carboxylate, methylcarboxylate, ethylcarboxylate, propylcarboxylate, isopropylcarboxylate, carboxaldehyde, acetoxy, propionyloxy, isopropionyloxy, cyano, aminomethyl, N-methylaminomethyl, N,N-dimethylaminomethyl, carboxamide, N-methylcarboxamide, N,N-dimethylcarboxamide, acetyl, propionyl, formyl, benzoyl, sulfate, methylsulfate, hydroxyl, methoxy, ethoxy, propoxy, isopropoxy, thiol, methylthio, ethylthio, propiothiol, fluoro, chloro, bromo, iodo, trifluoromethyl, propargyl, nitro, carbamoyl, ureido, azido, isocyanate, thioisocyanate, hydroxylamino, and nitroso.
A 2,6-substituted piperidino compound and pharmaceutically effective salts thereof, including resolved diasteriomers, enantiomers thereof, comprising formula (I):
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- wherein:
- R1 represents a hydrogen, methyl, deuteromethyl (CD3), tritiomethyl (CT3), ethyl, or C3-C7 straight chain or branched alkyl, C3-C6 cycloalkyl, vinyl, allyl, C4-C7 alkenyl, benzyl, and phenylethyl;
- R2 and R3 are each independently ortho-, meta-, or para-substituted moieties, where the substituted moiety is selected from the group consisting of hydrogen, methyl, ethyl, C3-C7 straight chain or branched alkyl, C3-C6 cycloalkyl, vinyl, allyl, C4-C7 alkenyl, benzyl, phenylethyl, N-methylamino, N,N-dimethylamino, carboxylate, methylcarboxylate, ethylcarboxylate, propylcarboxylate, isopropylcarboxylate, carboxaldehyde, acetoxy, propionyloxy, isopropionyloxy, cyano, aminomethyl, N-methylaminomethyl, N,N-dimethylaminomethyl, carboxamide, N-methylcarboxamide, N,N-dimethylcarboxamide, acetyl, propionyl, formyl, benzoyl, sulfate, methylsulfate, hydroxyl, methoxy, ethoxy, propoxy, isopropoxy, thiol, methylthio, ethylthio, propiothiol, fluoro, chloro, bromo, iodo, trifluoromethyl, propargyl, nitro, carbamoyl, ureido, azido, isocyanate, thioisocyanate, hydroxylamino, and nitroso.
A method of making a 2,6-substituted piperidino compound comprising formula (I):
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- wherein:
- R1 represents a hydrogen, methyl, deuteromethyl (CD3), tritiomethyl (CT3), ethyl, or C3-C7 straight chain or branched alkyl, C3-C6 cycloalkyl, vinyl, allyl, C4-C7 alkenyl, benzyl, and phenylethyl;
- R2 and R3 are each independently ortho-, meta-, or para-substituted moieties, where the substituted moiety is selected from the group consisting of hydrogen, methyl, ethyl, C3-C7 straight chain or branched alkyl, C3-C6 cycloalkyl, vinyl, allyl, C4-C7 alkenyl, benzyl, phenylethyl, N-methylamino, N,N-dimethylamino, carboxylate, methylcarboxylate, ethylcarboxylate, propylcarboxylate, isopropylcarboxylate, carboxaldehyde, acetoxy, propionyloxy, isopropionyloxy, cyano, aminomethyl, N-methylaminomethyl, N,N-dimethylaminomethyl, carboxamide, N-methylcarboxamide, N,N-dimethylcarboxamide, acetyl, propionyl, formyl, benzoyl, sulfate, methylsulfate, hydroxyl, methoxy, ethoxy, propoxy, isopropoxy, thiol, methylthio, ethylthio, propiothiol, fluoro, chloro, bromo, iodo, trifluoromethyl, propargyl, nitro, carbamoyl, ureido, azido, isocyanate, thioisocyanate, hydroxylamino, and nitroso;
- comprising the steps of treating a compound having the following formula (II):
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- with a boron hydride to form an intermediate compound having the following formula (III):
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- and treat the intermediate compound with an phosphoric acid to form diasterisomers and enantiomers of formula (I).
Dependencies are inferred from the claim text.