EP0289070A1 — Tertiary arylethyl amine derivatives having opiate-antagonistic activity

USPTO Abstract

The invention relates to a group of tertiary arylethyl amine derivatives having opiate-antagonistic activity. The compounds have the general formula 1 wherein R 1 is hydrogen, an optionally esterified hydroxyl group or mercapto group, a group -NHRs or -CONHR 9 , wherein R s is hydrogen, alkyl having 1-6 C-atoms or alkylcarbonyl having 1-7 C-atoms; R 2 is hydrogen or, when R 1 is hydrogen, one of the other meanings of Ri, or R 1 and R 2 together with the 2 carbon atoms of the benzene ring constitute a heterocyclic group which consists of five or six ring atoms and which comprises a group -NH-and, optionally may comprise an oxygen atom, sulphur atom or nitrogen atom as a second hetero atom; R 3 is hydrogen, alkyl, alkoxy or alkylthio having 1-4 C-atoms, amino, mono-or dialkylamino having 1-4 C-atoms per alkyl group, hydroxyalkyl, alkyl-, alkylamino-or alkoxycarbonyl having 1-4 C-atoms in the alkyl group, nitro, cyano, halogen, trifluoromethyl, trifluoromethoxy, alkylsulphonyl having 1-4 C-atoms, or aminosulphonyl; m has the value 1, 2 or 3; R 4 is hydrogen, alkyl or alkoxy having 1-3 C-atoms, or hydroxyl; R s is hydrogen; alkyl, phenylalkyl, hydroxyalkyl, methoxyalkyl, alkylcarbonyl, alkoxycarbonyl or alkylaminocarbonyl having 1-6 C-atoms in the optionally branched alkyl group; R 6 is straight or branched alkyl, alkenyl or cycloalkylalkyl or cycloalkyl, having at most 8 C-atoms; Y is a group R 7 -X-R 8 , wherein R 7 is a straight or branched alkylene chain having 3-8 C-atoms with at least 3 C-atoms between the nitrogen atom and group X; X is the carbonyl group or ketalised carbonyl group, or the group CHOH, CHC 6 H 5 , CH 2 , -CONH-or -CO-NCH 3 or an oxygen atom or sulphur atom; and R 8 is an alkyl group, cycloalkyl group or cycloalkylalkyl group having at most 10 C-atoms a phenyl group or phenylalkyl group having 1-4 C-atoms in the alkyl group, which groups Rs can be substituted with one or more groups R 3 ; or Y is a group of the formula 2a-2e wherein R 10 may have the meanings given for R 3 .