PIPERAZINE DERIVATIVES WHICH EXHIBIT ACTIVITY AS SEROTONIN AND NORADRENALINE RE-UPATKE INHIBITORS

摘要

A compound of formula (I), wherein R<1> is H; R<2> is aryl, het, C3-8cycloalkyl, C1-6alkyl, (CH2)zaryl or R<4>, wherein each of the cycloalkyl, aryl, het and R<4> groups is optionally substituted by at least one substituent independently selected from C1-6alkyl, C1-6alkoxy, OH, halo, CF3, OCF3, OCHF2, O(CH2)yCF3, CN, CONH2, CON(H)C1-6alkyl, CON(C1-6alkyl)2, hydroxy-C1-6alkyl, Cl-4alkoxy-C1-6alkyl, C1-4alkoxy-C1-4alkoxy, SCF3, C1-6alkyISO2, C1-4alkyl-S-Cl-4alkyl, C1-4alkyl-S-, C1-4alkyINR<10>R<11> and NR<10>R<11>; or R<1> and R<2>, together with the carbon atom to which they are bound, form a 5- or 6-membered carbocycle or a 5- or 6-membered heterocycle containing at least one N, O or S heteroatom; R<3> is aryl, het or R<4>, each optionally substituted by at least one substituent independently selected from C1-6alkyl, C1-6alkoxy, het, OH, halo, CF3, OCF3, OCHF2, O(CH2)yCF3, CN, CONH2, CON(H)C1-6alkyl, CON(C1-6alkyl)2, hydroxy-Cl-6alkyl, C1-4alkoxy-C1-6alkyl, C1-4alkoxy-C1-4 alkoxy, SCF3, C1-6alkyISO2, C1-4alkyl-S-C1-4alkyl, C1-4alkyl-S-, C1-4 alkylNR<10>R<11>and NR<10>R<11>; R<4> is a phenyl group fused to a 5- or 6­ membered carbocycle, or a phenyl group fused to a 5- or 6-membered heterocycle containing at least one N, O or S heteroatom; R<5> is H or C1- 6alkyl; R<10 >and R<11> are the same or different and are independently H or C1-4alkyl; A is a C1-3alkylene chain which is optionally substituted by OH, C1-4alkyl or C1-4alkoxy; x is an integer from 1 to 3; y is 1 or 2; z is an integer from 1 to 3; aryl is phenyl, naphthyl, anthracyl or phenanthryl; and het is an aromatic or non-aromatic 4-, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom, optionally fused to a 5- ­or 6-membered carbocycle or a second 4-, 5- or 6-membered heterocycle which contains at least one N, O or S heteroatom.