Tropane analogs and methods for inhibition of monoamine

A method for inhibiting 5-hydroxytryptamine reuptake of a monoamine transporter comprising contacting the monoamine transporter with a compound having the structural formula:

• 15
• 16
• wherein:
• R1=COOCH3, COR3, lower alkyl, lower alkenyl, lower alkynyl, CONHR4. or COR6;
• R2=is a 6α, 6β, 7α or 7β substituent, which can be selected from OH, OR3, F, Cl, Br, and NHR3;
• X=NR3, CH2, CHY, CYY1 CO, O, S;
• SO, SO2, NSO2R3, or C═CX1Y;
• X1=NR3, CH2, CHY, CYY1, CO, O, S;
• SO, SO2, or NSO2R3;
• R3=H, CH3, CH3CH2, CH3(CH2)n(CH2)nC6H4Y, C6H4Y, CHCH2, lower alkyl, lower alkenyl or lower alkynyl;
• Y and Y1=H, Br, Cl, I, F, OH, OCH3, CF3, NO2, NH2, CN, NHCOCH3, N(CH3)2, (CH2)nCH3, COCH3, or C(CH3)3;
• R4=CH3, CH2CH3, or CH3SO2;
• Ar=phenyl-R5, naphthyl-R5, anthracenyl-R5, phenanthrenyl-R5, or diphenylmethoxy-R5;
• R5=Br, Cl, I, F, OH, OCH3, CF3, NO2, NH2, CN, NHCOCH3, N(CH3)2, (CH2)nCH3, COCH3, C(CH3) where n=0-6, 4-F, 4-Cl, 4-I, 2-F, 2-Cl, 2-I, 3-F, 3-Cl, 3-I, 3,4-diCl, 3,4-diOH, 3,4-diOAc, 3,4-diOCH3, 3-OH-4-Cl, 3-OH-4-F, 3-C1-4-OH, 3-F-4-OH, lower alkyl, lower alkoxy, lower alkenyl, lower alkynyl, CO(lower alkyl), or CO(lower alkoxy);
• R6=morpholinyl or piperidinyl;
• m=0 or 1;
• n=0, 1, 2, 3, 4 or 5;
• and
• when X=O, CH2, CHY, CYY1 CO or C═CX1Y, R2 can be H;
• except that when X═N, R1 is not COR6.

A method for inhibiting 5-hydroxytryptamine reuptake of a monoamine transporter in a mammal comprising administering to the mammal a 5-hydroxytryptamine reuptake inhibiting amount of a compound having the structural formula:

• 17
• wherein:
• R1=COOCH3, COR3, lower alkyl, lower alkenyl, lower alkynyl, CONHR4, or COR6;
• R2 =is a 6α, 6β, 7α or 7β substituent, which can be selected from OH, OR3, F, Cl, Br, and NHR3;
• X=NR3, CH2, CHY, CYY1 CO, O, S;
• SO, SO2, NSO2R3, or C═CX1Y;
• X1=NR3, CH2, CHY, CYY1 CO, O, S;
• SO, SO2, or NSO2R3;
• R3=H, CH3, CH3CH2, CH3(CH2)n (CH2)nC6H4Y, C6H4Y, CHCH2, lower alkyl, lower alkenyl or lower alkynyl;
• Y and Y1=H, Br, Cl, I, F, OH, OCH3, CF3, NO2, NH2, CN, NHCOCH3, N(CH3)2, (CH2)nCH3, COCH3, or C(CH3)3;
• R4=CH3, CH2CH3, or CH3SO2;
• Ar=phenyl-R5, naphthyl-R5, anthracenyl-R5, phenanthrenyl-R5, or diphenylmethoxy-R5;
• R5=Br, Cl, I, F, OH, OCH3, CF3, NO2, NH2, CN, NHCOCH3, N(CH3)2, (CH2)nCH3, COCH3, C(CH3)3 where n=0-6, 4-F, 4-Cl, 4-I, 2-F, 2-Cl, 2-I, 3-F, 3-Cl, 3-I, 3,4-diCl, 3,4-diOH, 3,4-diOAc, 3,4-diOCH3, 3-OH-4-Cl, 3-OH-4-F, 3-Cl-4-OH, 3-F-4-OH, lower alkyl, lower alkoxy, lower alkenyl, lower alkynyl, CO(lower alkyl), or CO(lower alkoxy);
• R6=morpholinyl or piperidinyl;
• m=0 or 1;
• n=0, 1, 2, 3, 4 or 5;
• and
• when X=O, CH2, CHY, CYY1 CO or C═CX1Y, R2 can be H;
• except that when X═N, R1 is not COR6.

A method for inhibiting dopamine reuptake of a dopamine transporter in a mammal comprising administering to the mammal a dopamine reuptake inhibiting amount of a compound having the structural formula:

• 18
• wherein:
• R1=COOCH3, COR3, lower alkyl, lower alkenyl, lower alkynyl, CONHR4, or COR6;
• R2=is a 6α, 6β, 7α or 7β substituent, which can be selected from OH, OR3, F, Cl, Br, and NHR3;
• X=NR3, CH2, CHY, CYY1 CO, O, S;
• SO, SO2, NSO2R3, or C═CX1Y;
• X1=NR3, CH2, CHY, CYY1 CO, O, S;
• SO, SO2, or NSO2R3;
• R3=H, CH3, CH3CH2, CH3(CH2)n (CH2)nC6H4Y, C6H4Y, CHCH2, lower alkyl, lower alkenyl or lower alkynyl;
• Y and Y1=H, Br, Cl, I, F, OH, OCH3, CF3, NO2, NH2, CN, NHCOCH3, N(CH3)2, (CH2),CH3, COCH3, or C(CH3)3;
• R4=CH3, CH2CH3, or CH3SO2;
• Ar=phenyl-R5, naphthyl-R5, anthracenyl-R5, phenanthrenyl-R5, or diphenylmethoxy-R5;
• R5=Br, Cl, I, F, OH, OCH3, CF3, NO2l NH2, CN, NHCOCH3, N(CH3)2, (CH2)nCH3, COCH3, C(CH3)3 where n=0-6, 4-F, 4-Cl, 4-I, 2-F, 2-Cl, 2-I, 3-F, 3-Cl, 3-I, 3,4-diCl, 3,4-diOH, 3,4-diOAc, 3,4-diOCH3, 3-OH-4-Cl, 3-OH-4-F, 3-Cl-4-OH, 3-F-4-OH, lower alkyl, lower alkoxy, lower alkenyl, lower alkynyl, CO(lower alkyl), or CO(lower alkoxy);
• R6=morpholinyl or piperidinyl;
• m=0 or 1;
• n=0, 1, 2, 3, 4 or 5;
• and
• when X=O, CH2, CHY, CYY1 CO or C═CX1Y, R2 can be H;
• except that when X═N, R1 is not COR6.