8-carboxamido-2,6-methano-3-benzazocines
AssigneeRensselaer Polytechnic Inst.
InventorMark P. Wentland
Life of this patent
Estimating the term…
Abstract
8-Substituted-2,6-methano-3-benzazocines of general structure I in which A is —CH2—OH, —CH2NH2, —NHSO2CH3, and Y is O, S or NOH are useful as analgesics, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications. 8-Carboxamides, thiocarboxamides, hydroxyamidines and formamides are preferred.
Claims13
A morphinan having the structure:
- wherein
- A is chosen from CN—CH2—Z, —NHSO2-(loweralkyl),
- Q is chosen from O, S and NR17;
- Y is chosen from O, S, NR17 and NOH;
- Z is chosen from OH, SH, CN and NH2;
- R1 is chosen from hydrogen, lower alkoxy, phenyl and —NHR8;
- R2 and R2a are both hydrogen or taken together R2 and R2a are ═O;
- R3 is chosen from hydroyen, lower alkyl, alkenyl, benzyl, aryl, heterocyclyl and hydroxyalkyl;
- R4 is chosen from hydrogen, hydroxy, amino, lower alkoxy, C1-C20 alkyl and C1-C20 alkyl substituted with hydroxy or carbonyl;
- R8 is chosen from hydrogen, —OH, —NH2 and —CH2R15;
- R9 is hydrogen or lower alkyl;
- R10 is chosen from hydrogen, lower alkyl and hydroxy(lower alkyl);
- or
- together, R9 and R10 form a spiro-fused carbocycle of 5 to 10 carbons;
- R11 is hydrogen;
- R12 is chosen from hydroxy, lower alkoxy, —NH2, —N(CH2CH2Cl)2, and —NHC(O)CH═CHCOOCH3;
- or
- together, R11 and R12 form a carbonyl or a vinyl substituent;
- R15 is chosen from hydrogen, alkyl, aryl, substituted aryl and alkyl substituted with alkoxy, amino, alkylamino or dialkylamino;
- R16 is chosen from hydropen and NH2;
- and
- R17 is chosen from hydrogen, alkyl, aryl and benzyl;
- with the proviso that, when R2 and R2a are hydrogen, R3 is hydrogen or cyclouropyl, R4 is hydroxy, and together R11 and R12 form a carbonyl, A cannot be NHSO2CH3.
A method for treating a disease or condition chosen from the group consisting of pain, pruritis, diarrhea, irritable bowel syndrome, gastrointestinal motility disorder, obesity, respiratory depression, convulsions, coughing, hyperalgesia and drug addiction comprising administering to a patient in need of such treatment a therapeutically effective amount of a compound having the structure:
- wherein
- A is chosen from —CH2—Z, —NHSO2-(loweralkyl),
- Q is chosen from O, S and NR17;
- Y is chosen from O, S, NR17 and NOH;
- Z is chosen from OH, SH, CN and NH2;
- R1 is chosen from hydrogen, lower alkoxy, phenyl and —NHR8;
- R2 and R2a are both hydrogen or taken together R2 and R2a are ═O;
- R3 is chosen from hydrogen, lower alkyl, alkenyl, benzyl, aryl, heterocyclyl and hydroxyalkyl;
- R4 is chosen from hydrogen, hydroxy, amino, lower alkoxy, C1-C20 alkyl and C1-C20 alkyl substituted with hydroxy or carbonyl;
- R8 is chosen from hydrogen, —OH, —NH2 and —CH2R15;
- R9 is hydrogen or lower alkyl;
- R10 is chosen from hydrogen, lower alkyl and hydroxy(lower alkyl);
- or
- together, R9 and R10 form a spiro-fused carbocycle of 5 to 10 carbons;
- R11 is hydrogen;
- R12 is chosen from hydroxy, lower alkoxy, —NH2, —N(CH2CH2Cl)2, and —NHC(O)CH═CHCOOCH3;
- or
- together, R11 and R12 form a carbonyl or a vinyl substituent;
- R15 is chosen from hydrogen, alkyl, aryl, substituted aryl and alkyl substituted with alkoxy, amino, alkylamino or dialkylamino;
- R16 is chosen from hydrogen and NH2;
- and
- R17 is chosen from hydrogen, alkyl, aryl and benzyl;
- with the proviso that, when R2 and R2a are hydrogen, R3 is hydrogen or cyclopropyl, R4 is hydroxy, and together R11 and R12 form a carbonyl, A cannot be NHSO2CH3.
Dependencies are inferred from the claim text.