Substituted noribogaine
AssigneeDemerx, Inc.
InventorsDeborah C. Mash, Richard D. Gless, Jr., Robert M. Moriarty
Life of this patent
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Abstract
This invention relates noribogaine derivatives, compositions and methods of use thereof.
Claims6
A method for treating pain in a patient which method comprises administering an effective amount of a compound of Formula IA, a pharmaceutically acceptable salt of each thereof, or a pharmaceutical composition comprising a compound of Formula IA 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;
- 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:
- when R is —OH or C1-C12 alkyl optionally substituted with 1 to 5 R9, then R3 is hydrogen;
- and
- 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, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula IIB or a pharmaceutically acceptable salt thereof:
- wherein
- R11 is —SH or —S(O)2N(R16)2;
- and
- each R16 is independently hydrogen or C1-C12 alkyl optionally substituted with from 1 to 3 halo.
A method for treating pain in a patient which method comprises administering an effective amount of a compound of Formula IIF-i, a pharmaceutically acceptable salt thereof, or a pharmaceutical composition comprising a compound of Formula IIF-i or a pharmaceutically acceptable salt thereof:
- wherein the compound is selected from the group consisting of compounds wherein R22, R12 and R13 are defined as follows:
- No.
- R22
- R12
- R13
- 6
- —OC(O)OCH2CH3
- H
- H
- 7
- —OC(O)OCH2Ph
- H
- H
- 8
- —OC(O)NH(CH(CH3)Ph)
- H
- H
- 9
- —OC(NPh)NHCH2CH3
- H
- H
- 10
- —OC(O)NHCH2Ph
- H
- H
- 12
- —NHC(O)C(CH3)3
- H
- H
- 13
- —NHC(O)CF3
- H
- H
- 14
- —NHC(O)CH2Ph
- H
- H
- 15
- —NHC(O)OCH2Ph
- H
- H
- 16
- —NHC(O)NH(CH(CH3)Ph)
- H
- H
- 17
- —SH
- H
- H
- 18
- —SC(O)OCH2Ph
- H
- H
- 19
- —SC(O)NH(CH(CH3)Ph)
- H
- H
- 20
- —SC(O)CH2CH2OP(O)(OH)2
- H
- H
- 21
- —OC(O)CH2CH2CH(NH2)(CO2H)
- H
- H
- 22
- —O-(2-OH—C6H3)CH2CH(NH2)(CO2H)
- H
- H
- 23
- —NHC(O)CH2CH2CH(NH2)(CO2H)
- H
- H
- 37
- —OH
- —CH2CH3
- H
- 38
- —OH
- —CH2CHCH2
- H
- 39
- —OH
- —CH2Ph
- H
- 40
- —OH
- —C(O)O(CH2)2N(CH3)2
- H
- 41
- —OH
- —C(O)CH2(CH2)2SO2N(CH3)2
- H
- 42
- —OH
- H
- —OCH2CH3
- 43
- —OH
- H
- —OCH2Ph
- 44
- —OH
- H
- —CF3
- 45
- —OH
- H
- —OH
- 46
- —OH
- H
- —CN.
Dependencies are inferred from the claim text.