Patent ID: 6451806
Filing Date: 2002-09-17
Classification: A61K

Abstract:
A method of preventing or treating a side effect associated with an opioid comprising administering to a patient, in combination with an effective amount of an opioid, an effective amount of a compound of the following formula (I): wherein:R1 is hydrogen or alkyl; R2 is hydrogen, alkyl or alkenyl; R3 is hydrogen, alkcyl, alkenyl, aryl, cycloalkyl, cycloalkenyl, cycloalkyl-substituted alkyl, cycloalkenyl-substituted alkyl or aryl-substituted alkyl; R4 is hydrogen, alkyl or alkenyl; A is OR5 or NR6R7; wherein: R5 is hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkyl-substituted alkyl, cycloalkenyl-substituted alkyl, or aryl-substituted alkyl; R6 is hydrogen or alkyl; R7 is hydrogen, alkyl, alkenyl, cycloalkyl, aryl, cycloalkyl-substituted alkyl, cycloalkenyl, cycloalkenyl-substituted alkyl, aryl-substituted alkyl, aryl-substituted alkyl, or alkylene substitued B or, together with the nitrogen atom to which they are attached, R6 and R7 form a heterocyclic ring; B is C(&boxH;O)W or NR8R9; wherein;R8 is hydrogen or alkyl; R9 is hydrogen, alkyl, alkenyl, cycloalkyl-substituted alkyl, cycloalkyl, cycloalkenyl, cycloalkenyl-substituted alkyl, aryl or aryl-substituted alkyl or, together with the nitrogen atom to which they are attached, R8 and R9 form a heterocyclic ring; W is OR10, NR11R12, or OE; wherein R10 is hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkyl-substituted alkyl, cycloalkenyl-substituted alkyl, or aryl-substituted alkyl; R11 is hydrogen or alkyl; R12 is hydrogen, alkyl, alkenyl, aryl, cycloalkyl, cycloalkenyl, cycloalkyl-substituted alkyl, cycloalkenyl-substituted alkyl, aryl-substituted alkyl or alkylene substituted C(&boxH;O)Y or, together with the nitrogen atom to which they are attached, R11 and R12 form a heterocyclic ring; E is alkylene substituted (C&boxH;O)D, or â€”R13OC(&boxH;O)R14;whereinR13 is alkyl substituted alkylene; R14 is alkyl; D is OR15 or NR16R17; wherein:R15 is hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkyl-substituted alkyl, cycloalkenyl-substituted alkyl, or aryl-substituted alkyl; R16 is hydrogen, alkyl, alkenyl, aryl, aryl-substituted alkyl, cycloalkyl, cycloalkenyl, cycloalkyl-substituted alkyl or cycloalkenyl-substituted alkyl; R17 is hydrogen or alkyl or, together with the nitrogen atom to which they are attached, R16 and R17 form a heterocyclic ring; Y is OR18 or NR19R20; wherein:R18 is hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, cycloalkyl-substituted alkyl, cycloalkenyl-substituted alkyl, or aryl-substituted alkyl; R19 is hydrogen or alkyl; R20 is hydrogen, alkyl, alkenyl, aryl, cycloalkyl, cycloalkenyl, cycloalkyl-substituted alkyl, cycloalkenyl-substituted alkyl, or aryl-substituted alkyl or, together with the nitrogen atom to which they are attached, R19 and R20 form a heterocyclic ring; R21 is hydrogen or alkyl; and n is 0 to 4; or a stereoisomer, prodrug, or pharmaceutically acceptable salt, hydrate or N-oxide thereof.