Kappa agonist compounds, pharmaceutical formulations and method of prevention and treatment of pruritus therewith
AssigneeAdolor Corporation
InventorsWei Yuan Zhang, Alan L. Maycock, Anthony Michael Marella, Virendra Kumar, Forrest Gaul, Deqi Guo
Life of this patent
Estimating the term…
Abstract
Method for the prevention or treatment of pruritus with anti-pruritic compounds is provided. The compounds of formulae I, II, IIA, III, IIIA, IV and IVA have the structure: wherein R1, R2, R3, R4; and X, X4, X5, X7, X9; Y, Z and n are as described in the specification.
Claims2
A method for the prevention or treatment of pruitus in a patient comprising administering to said patient an effective amount of a compound of formula IVA or a pharmaceutically acceptable salt thereof
- wherein
- n=1-3;
- R1 and R2 are independently—(CH2)m, where m is an interger from 4 to 8;
- —CH2CH(OR)(CH2)2—, wherein R=H, alkyl, acyl, or aroyl;
- CH2CH(F)(CH2)2—;
- —(CH2)2O(CH2)2—;
- or —(CH2)2CH═CHCH2—;
- R3 and R4 are independently H;
- OCH3;
- alkyl;
- or —O(CH2)2;
- X9=1-4 substituents selected from the groups consisting of -halogen;
- —CF3;
- OH;
- —OCH3;
- —SO2NH(CH2)qCH3;
- —NH(CH2)qCOR′;
- —NH(CH2)q(CH═CH)q(CH2)qCO2R′;
- —NH(CH)q(CH≡CH)q(CH)qCO2R;
- —NHCO(CH2)q(CH═CH)q(CH2)qCO2R;
- and —NHCO(CH)q(CH═CH)q(CH)qCO2R′;
- wherein
- q=0-20 and
- R′=OH, lower alkyl, aryl ester or aryl amide, in a pharmaceutically acceptable carrier.
A method for the prevention or treatment of pruritus in a patient comprising administering to said patient an effective amount of a compound selected from the group consisting of:
- (Z)-4-[2-((±)-trans-2-Amino-4,5-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]phenylaetamido)]4-oxo-2-butenoic acid;
- (Z)-4-[2-((±)-trans-2-Amino-4-trifuoromethyl-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]phenylaetamido)]4oxo-2-butenoic acid;
- (±)-trans-2-N-Methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-pyridylacetamide dihydrochloride;
- (±)-trans-3-N-Methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-5-bromo-pyridylacetamide hydrochloride;
- (±)-trans-3,5-Di-Trifluoromethyl-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]phenylacetamide hydrochloride;
- (±)-trans-3-N-Methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-(trans-3-furyl)acetamide hydrochloride;
- (±)-trans-2-Methoxy-3-methylsulfamoyl-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]phenylacetamide hydrochloride;
- (±)-trans-3-N-Methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]indoleacetamide hydrochloride;
- N-[1S, 2S-trans-4-Trifluoromethyl-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]phenylacetamido]glycine Hydrochloride;
- N-[1R, 2R-trans-4-Trifluoromethyl-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]phenylacetamido]glycine hydrochloride;
- and
- (±)-trans-4-Fluoro-3-methylsulfamoyl-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]phenylacetamide hydrochloride.
Dependencies are inferred from the claim text.