公开(公告)号：EP0289070A1

公开(公告)日：1988-11-02

申请号：EP88200648.9

申请日：1988-04-06

申请人： DUPHAR INTERNATIONAL RESEARCH B.V

发明人： Van Wijngaarden, Ineke ,  Den Hartog, Jacobus A. J. ,  Tulp, Martinus T. M. ,  Lobbezoo, Marinus W.

IPC分类号： C07C215/52 ,  C07C215/60 ,  C07C225/00 ,  C07C237/20 ,  C07D207/335 ,  C07D231/12 ,  A61K31/135 ,  A61K31/16 ,  A61K31/40 ,  A61K31/415

CPC分类号： C07D231/12

摘要： 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 .

摘要翻译： 本发明涉及具有阿片拮抗作用的一组叔芳基乙基胺衍生物。 该化合物具有通式1 其中R 1是氢，任意酯化的羟基或巯基，-NHR 9或-CONHR 9基团，其中R 9是氢，具有1-6个C原子的烷基或具有1- 7个C原子; R 2为氢或R 1为氢时，R 1，R 1和R 2与苯环的2个碳原子的其它含义之一构成由5或6个环原子组成的杂环基， NH-，并且任选地可以包含氧原子，硫原子或氮原子作为第二杂原子; R3是氢，烷基，烷氧基或具有1-4个C原子的烷硫基，氨基，每个烷基具有1-4个C原子的单或二烷基氨基，具有1-4个C原子的羟烷基，烷基 - ，烷基氨基或烷氧基羰基 在烷基中，硝基，氰基，卤素，三氟甲基，三氟甲氧基，具有1-4个C原子的烷基磺酰基，或氨基磺酰基; m的值为1,2或3; R4是氢，具有1-3个C原子的烷基或烷氧基，或羟基; R5是氢; 烷基，苯基烷基，羟基烷基，甲氧基烷基，烷基羰基，烷氧基羰基或具有1-6个C原子的烷基氨基羰基; R6是具有至多8个C原子的直链或支链烷基，烯基或环烷基烷基或环烷基; Y是R7-X-R8基团，其中R7是在氮原子和基团X之间具有3-8个碳原子和至少3个C原子的直链或支链亚烷基链; X是羰基或缩酮化羰基，或CHOH，CHC6H5，CH2，-CONH-或-CO-NCH3基团或氧原子或硫原子; R8是烷基中具有至多10个碳原子的烷基，环烷基或环烷基烷基，该烷基中具有1-4个C原子的苯基或苯基烷基，该基团R8可被一个或多个R 3基团取代; 或Y是式2a-2e 的基团，其中R 10可具有R3给出的含义。 一个