Spirocyclic ligands for sigma receptors, and libraries and methods of use thereof

A compound represented by structure 2:

• 69
• wherein
• R represents independently for each occurrence hydrogen, alkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl;
• R1 is absent, or present between 1 and 4 times;
• R1 represents independently for each occurrence halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, sulfhydryl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, nitrile, guanidine, amidine, acetal, ketal, amine oxide, aryl, heteroaryl, aralkyl, heteroaralkyl, azide, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or —(CH2)m—R80;
• R2 and R3 represent independently for each occurrence hydrogen, alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, OR, N(R)2, CO2R, C(O)N(R)2, OC(O)R, or N(R)C(O)R;
• or the geminal instances of R2 and R3 taken together may represent O or C(R)2;
• R6 represents hydrogen, alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, C(O)OR, C(O)N(R)2, or SO2R;
• R7 represents hydrogen, alkyl, alkenyl, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, C(O)OR, C(O)N(R)2, or SO2R;
• R80 represents an aryl, cycloalkyl, cycloalkenyl, heterocyclyl, or polycyclyl group;
• and
• m is an integer in the range 0 to 8 inclusive;
• provided that when the geminal instances of R2 and R3 taken together represent O, R7 is not acetyl.

A compound represented by structure 3:

• 70
• wherein
• R represents independently for each occurrence hydrogen, alkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl;
• R1 is absent, or present between 1 and 4 times;
• R1 represents independently for each occurrence halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, sulfhydryl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, nitrile, guanidine, amidine, acetal, ketal, amine oxide, aryl, heteroaryl, aralkyl, heteroaralkyl, azide, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or —(CH2)m—R80;
• R2 and R3 represent independently for each occurrence hydrogen, alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, OR, N(R)2, CO2R, C(O)N(R)2, OC(O)R, or N(R)C(O)R;
• or the geminal instances of R2 and R3 taken together may represent O or C(R)2;
• R4 represents independently for each occurrence H or alkyl;
• R6 represents hydrogen, alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, C(O)OR, C(O)N(R)2, or SO2R;
• R7 represents hydrogen, alkyl, alkenyl, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, C(O)OR, C(O)N(R)2, or SO2R;
• R80 represents an aryl, cycloalkyl, cycloalkenyl, heterocyclyl, or polycyclyl group;
• m is an integer in the range 0 to 8 inclusive;
• and
• n is 0 or 1;
• provided that when the geminal instances of R2 and R3 taken together represent O, R7 is not acetyl.

A compound represented by structure 4:

• 71
• wherein
• R represents independently for each occurrence hydrogen, alkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl;
• R1 is absent, or present between 1 and 4 times;
• R1 represents independently for each occurrence halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, sulfhydryl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, nitrile, guanidine, amidine, acetal, ketal, amine oxide, aryl, heteroaryl, aralkyl, heteroaralkyl, azide, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or —(CH2)m—R80;
• R2 and R3 represent independently for each occurrence hydrogen, alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, OR, N(R)2, CO2R, C(O)N(R)2, OC(O)R, or N(R)C(O)R;
• or the geminal instances of R2 and R3 taken together may represent O or C(R)2;
• R6 represents hydrogen, alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, C(O)OR, C(O)N(R)2, or SO2R;
• R7 represents hydrogen, alkyl, alkenyl, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, C(O)OR, C(O)N(R)2, or SO2R;
• R80 represents an aryl, cycloalkyl, cycloalkenyl, heterocyclyl, or polycyclyl group;
• and
• m is an integer in the range 0 to 8 inclusive;
• provided that R2 and R3 are not both methyl;
• or R6 and R7 are not both acetyl.

A compound represented by structure 5:

• 72
• wherein
• R represents independently for each occurrence hydrogen, alkyl, aryl, heteroaryl, aralkyl, or heteroaralkyl;
• R1 is absent, or present between 1 and 4 times;
• R1 represents independently for each occurrence halogen, alkyl, alkenyl, alkynyl, hydroxyl, alkoxyl, silyloxy, amino, nitro, sulfhydryl, alkylthio, imine, amide, phosphoryl, phosphonate, phosphine, carbonyl, carboxyl, carboxamide, anhydride, silyl, thioalkyl, alkylsulfonyl, arylsulfonyl, selenoalkyl, ketone, aldehyde, ester, heteroalkyl, nitrile, guanidine, amidine, acetal, ketal, amine oxide, aryl, heteroaryl, aralkyl, heteroaralkyl, azide, aziridine, carbamate, epoxide, hydroxamic acid, imide, oxime, sulfonamide, thioamide, thiocarbamate, urea, thiourea, or —(CH2)m—R80;
• R2 and R3 represent independently for each occurrence hydrogen, alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, OR, N(R)2, CO2R, C(O)N(R)2, OC(O)R, or N(R)C(O)R;
• or the geminal instances of R2 and R3 taken together may represent O or C(R)2;
• R6 represents hydrogen, alkyl, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, C(O)OR, C(O)N(R)2, or SO2R;
• R7 represents hydrogen, alkyl, alkenyl, aryl, heteroaryl, aralkyl, heteroaralkyl, acyl, C(O)OR, C(O)N(R)2, or SO2R;
• R80 represents an aryl, cycloalkyl, cycloalkenyl, heterocyclyl, or polycyclyl group;
• and
• m is an integer in the range 0 to 8 inclusive.