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US 6,469,030 B2Granted
Methods for the treatment and prevention of ileus
AssigneeAdolor Corporation
InventorsJohn J. Farrar, Peter J. Schied, William K. Schmidt, Randall L. Carpenter
Life of this patent
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Abstract
Methods for the treatment and/or prevention of ileus are disclosed. The methods comprise administering to a patient an effective amount of a peripheral mu opioid antagonist compound. Preferred compounds for use in the methods include piperidine-N-alkylcarboxylates.
Claims26
A method of treating or preventing ileus comprising administering to a patient 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, alkyl, 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 selected from pyrrole and piperidine;
- B is
- C(═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 selected from pyrrole and piperidine;
- 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(═O)Y or, together with the nitrogen atom to which they are attached, R11 and R12 form a heterocyclic ring selected from pyrrole and piperidine;
- E is
- alkylene substituted (C═O)D, or —R13OC(═O)R14;
- wherein
- R13 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 selected from pyrrole and piperidine;
- 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 selected from pyrrole and piperidine;
- R21 is hydrogen or alkyl;
- and
- n is 0 to 4;
- or a stereoisomer, prodrug, or pharmaceutically acceptable salt, hydrate or N-oxide thereof.
36 more elements
Dependencies are inferred from the claim text.