Hydroxybupropion analogues for treating drug dependence

摘要

The invention provides hydroxybupropion analogues capable of inhibiting the reuptake of one or more monoamines and/or acting as antagonists at nicotinic acetylcholine receptors. The compounds may selectively bind to one or more monoamine transporters, including those for dopamine, norepinephrine, and serotonin and/or may selectively bind to one or more nicotinic acetylcholine receptor subtypes. Such compounds may be used to treat conditions that are responsive to modification of monoamine levels and/or antagonism of nicotinic acetylcholine receptors, including drug dependency, depression, and obesity.

主权项

1. A compound according to the structure:wherein:
R1 is optionally substituted C1-10 alkyl; R2 is H or optionally substituted C1-10 alkyl; R3 and R4 are each independently selected from optionally substituted C1-10 alkyl; X, Y, and Z are each independently selected from H; optionally substituted C1-10 alkyl; optionally substituted C1-10 alkoxy; optionally substituted C2-10 alkenyl; optionally substituted C2-10 alkynyl; optionally substituted C6-C12 aryl; alkaryl; arylalkyl; aryloxy; optionally substituted heteroaryl; optionally substituted heterocycle; halo; hydroxyl; halogenated alkyl; an amino group of formula NH2, NR12H, or NR12R13; alkylamino; arylamino; acyl; CN; NO2; N3; CH2OH; CONH2; CONR12R13; CO2R12; CH2OR12; NHCOR12; NHCO2R12; C1-3 alkylthio; sulfate; sulfonic acid; sulfonate ester; phosphonic acid; phosphate; phosphonate; mono-, di-, or triphosphate ester; trityl or monomethoxytrityl; R12SO; R12SO2; CF3S; CF3SO2; trialkylsilyl; and diphenylmethylsilyl; and R12 and R13 are each independently selected from H or optionally substituted C1-10 alkyl; wherein one or more of X, Y, and Z are optionally substituted C6-C12 aryl, or a pharmaceutically acceptable ester, amide, salt, solvate, prodrug, or stereoisomer thereof.