Antipruritic
AssigneeToray Industries, Inc.
InventorsHiroshi Nagase, Takashi Endoh, Toshiaki Tanaka, Kuniaki Kawamura
Life of this patent
Estimating the term…
Abstract
This invention provides an antipuritic comprising an opiate κ receptor agonist as an effective component, a new morphian quaternary ammonium salt derivative and a new morphian-N-oxide derivative which are useful in treating puritus complicated with some diseases.
Claims13
An antipruritic comprising a morphinan-N-oxide derivative or its pharmacologically acceptable salt with an added acid represented by the general formula (III):
- wherein—is a double bond, or a single bond;
- R1 is alkyl having 1 to 5 carbon atoms, cycloalkylalkyl having 4 to 7 carbon atoms, cycloalkenylalkyl having 5 to 7 carbon atoms, aralkyl having 7 to 13 carbon atoms, alkenyl having 4 to 7 carbon atoms, or allyl;
- R2 is hydrogen, hydroxy, nitro, alkanoyloxy having 1 to 5 carbon atoms, alkoxy having 1 to 5 carbon atoms or alkyl having 1 to 5 carbon atoms;
- R3 is hydrogen, hydroxy, alkanoyloxy having 1 to 5 carbon atoms, or alkoxy having 1 to 5 carbon atoms;
- R4 is hydrogen, a straight or branched alkyl having 1 to 5 carbon atoms, or aryl having 6 to 12 carbon atoms;
- A is alkylene having 1 to 6 carbon atoms, —CH═CH—, or —C≡C—;
- and R5 is an organic group having any one of the following fundamental structures:
- wherein the organic group may have at least one substituent selected from the group consisting of alkyl having 1 to 5 carbon atoms, alkoxy having 1 to 5 carbon atoms, alkanoyloxy having 1 to 5 carbon atoms, hydroxy, fluorine, chlorine, bromine, iodine, nitro, cyano, isothiocyanato, trifluoromethyl, trifluoromethoxy, and methylenedioxy;
- and the general formula (III) comprises (+), (−), and (±) isomers.
A morphinan-N-oxide derivative or its pharmacologically acceptable salt with an added acid represented by the general formula (III):
- wherein—is a double bond or a single bond;
- R1 is alkyl having 1 to 5 carbon atoms, cycloalkylalkyl having 4 to 7 carbon atoms, cycloalkenylalkyl having 5 to 7 carbon atoms, aralkyl having 7 to 13 carbon atoms, alkenyl having 4 to 7 carbon atoms, or allyl;
- R2 is hydrogen, hydroxy, nitro, alkanoyloxy having 1 to 5 carbon atoms, alkoxy having 1 to 5 carbon atoms, or alkyl having 1 to 5 carbon atoms;
- R3 is hydrogen, hydroxy, alkanoyloxy having 1 to 5 carbon atoms, or alkoxy having 1 to 5 carbon atoms;
- R4 is hydrogen, a straight or branched alkyl having 1 to 5 carbon atoms, or aryl having 6 to 12 carbon atoms;
- A is alkylene having 1 to 6 carbon atoms, —CH═CH—, or —C≡C—;
- and R5 is an organic group having any one of the following fundamental structures:
- wherein the organic group may have at least one substituent selected from the group consisting of alkyl having 1 to 5 carbon atoms, alkoxy having 1 to 5 carbon atoms, alkanoyloxy having 1 to 5 carbon atoms, hydroxy, fluorine, chlorine, bromine, iodine, nitro, cyano, isothiocyanato, trifluoromethyl, trifluoromethoxy and methylenedioxy;
- and the general formula (III) comprises (+), (−), and (±) isomers.
A method for preparing a compound represented by the general formula (III) comprising oxidizing a tertiary amine represented by the general formula (IX) with an oxidizing reagent:
- wherein in the above general formulas (IX) and (III),—is a double bond, or a single bond;
- R1 is alkyl having 1 to 5 carbon atoms, cycloalkylalkyl having 4 to 7 carbon atoms, cycloalkenylalkyl having 5 to 7 carbon atoms, aralkyl having 7 to 13 carbon atoms, alkenyl having 4 to 7 carbon atoms, or allyl;
- R2 is hydrogen, hydroxy, nitro, alkanoyloxy having 1 to 5 carbon atoms, alkoxy having 1 to 5 carbon atoms or alkyl having 1 to 5 carbon atoms;
- R3 is hydrogen, hydroxy, alkanoyloxy having 1 to 5 carbon atoms, or alkoxy having 1 to 5 carbon atoms;
- R4is hydrogen, a straight or branched alkyl having 1 to 5 carbon atoms, or aryl having 6 to 12 carbon atoms;
- A is alkylene having 1 to 6 carbon atoms, —CH═CH— or —C≡C—;
- and R5 is an organic group having any one of the following fundamental structures:
- wherein the organic group may have at least one substituent selected from the group consisting of alkyl having 1 to 5 carbon atoms, alkoxy having 1 to 5 carbon atoms, alkanoyloxy having 1 to 5 carbon atoms, hydroxy, fluorine, chlorine, bromine, iodine, nitro, cyano, isothiocyanato, trifluoromethyl, trifluoromethoxy, and methylenedioxy.
Dependencies are inferred from the claim text.