Substituted noribogaine

A method for treating pain in a patient which method comprises administering an effective amount of a compound of Formula IA or Formula IB, a pharmaceutically acceptable salt of each thereof, or a pharmaceutical composition comprising a compound of Formula IA or Formula IB or a pharmaceutically acceptable salt thereof:

• wherein
• R is OR1 or C1-C12 alkyl optionally substituted with 1 to 5 R9;
• R1 is selected from the group consisting of hydrogen, —C(O)OX and —C(O)N(Y)2 where X is C1-C6 alkyl optionally substituted with 1 to 5 R9, and each Y is independently selected from the group consisting of hydrogen, C1-C6 alkyl optionally substituted with 1 to 5 R9, C6-C14 aryl optionally substituted with 1 to 5 R9, C3-C10 cycloalkyl optionally substituted with 1 to 5 R9, C1-C10 heteroaryl having 1 to 4 heteroatoms and which is optionally substituted with 1 to 5 R9, C1-C10 heterocyclic having 1 to 4 heteroatoms and which is optionally substituted with 1 to 5 R9, or where each Y, together with the nitrogen atom bound thereto form either a C1-C6 heterocyclic having 1 to 4 heteroatoms and which is optionally substituted with 1 to 5 R9, or a C1-C6 heteroaryl having 1 to 4 heteroatoms and which is optionally substituted with 1 to 5 R9;
• R′ is halo, OR20, or C1-C12 alkyl optionally substituted with 1 to 5 R9;
• R20 is selected from the group consisting of hydrogen, —C(O)X, —C(O)OX and —C(O)N(Y)2 where X and Y are defined as above;
• R2 is hydrogen;
• R3 is selected from the group consisting of hydrogen, —(CH2)mOR7, —CR6(OH)R7, —(CH2)mCN, —(CH2)mCOR7, —(CH2)mCO2R7, —(CH2)mC(O)NR6R7, —(CH2)mC(O)NR6NR7R7, —(CH2)mC(O)NR6NR7C(O)R8, and —(CH2)mNR6R7;
• m is 0, 1, or 2;
• L is a bond or C1-C12 alkylene;
• R4 is selected from the group consisting of, C1-C12 alkyl substituted with 1 to 5 R9, C2-C12 alkenyl substituted with 1 to 5 R9, —X2—R6, —(X2—Y2)n—X2—R6, —SO2NR6R7, —O—C(O)R8, —C(O)OR7, —C(O)NR6R7, —NR6R7, —NHC(O)R8, and —NR6C(O)R8;
• X2 is selected from the group consisting of O and S;
• Y2 is C1-C4 alkylene or C6-C10 arylene, or a combination thereof;
• n is 1, 2, or 3;
• R6 and R7 are each independently selected from the group consisting of hydrogen, C1-C12 alkyl optionally substituted with 1 to 5 R9, C1-C6 heterocycle having 1 to 4 heteroatoms and which is optionally substituted with 1 to 5 R9, C3-C10 cycloalkyl optionally substituted with 1 to 5 R9, C6-C10 aryl optionally substituted with 1 to 5 R9 and C1-C6 heteroaryl having 1 to 4 heteroatoms optionally substituted with 1 to 5 R9;
• R8 is selected from the group consisting of C1-C12 alkyl optionally substituted with 1 to 5 R9, C1-C6 heterocycle having 1 to 4 heteroatoms optionally substituted with 1 to 5 R9, C3-C10 cycloalkyl optionally substituted with 1 to 5 R9, C6-C10 aryl optionally substituted with 1 to 5 R9 and C1-C6 heteroaryl having 1 to 4 heteroatoms optionally substituted with 1 to 5 R9;
• R9 is selected from the group consisting of C1-C4 alkyl, phenyl, halo, —OR10, —CN, —COR10, —CO2R10, —C(O)NHR10, —NR10R10, —C(O)NR10R10, —C(O)NHNHR10, —C(O)NR10NHR10, —C(O)NR10NR10R10, —C(O)NHNR10C(O)R10, —C(O)NHNHC(O)R10, —SO2NR10R10, —C(O)NR10NR10C(O)R10, and —C(O)NR10NHC(O)R10;
• and
• R10 is C1-C12 alkyl;
• provided that:
• for the compound of Formula IA, when R is —OH or C1-C12 alkyl optionally substituted with 1 to 5 R9, then R3 is hydrogen;
• and
• for the compound of Formula IA, when R3 is hydrogen, and -L-R4 is ethyl, then R is not —OR1.

A method for treating pain in a patient which method comprises administering an effective amount of a compound of Formula IIB or Formula IIC, a pharmaceutically acceptable salt of each thereof, or a pharmaceutical composition comprising a compound of Formula IIB or Formula IIC or a pharmaceutically acceptable salt thereof:

• wherein
• R11 is —SH or —S(O)2N(R16)2;
• R21 is halo, —OH, —SH, —NH2, or —S(O)2N(R16)2;
• and
• each R16 is independently hydrogen or C1-C12 alkyl optionally substituted with from 1 to 3 halo.