| 摘要 |
A tetrahydronaphthalene or tetrahydroisoquinoline derivative of formula I, an optical or geometric isomer, a pharmacologically acceptable acid addition salt, N-oxide, ester or quaternary ammonium salt thereof is used in the manufacture of a medicament for treating atherosclerosis which is independent of lipid lowering. In formula I: A is CH2 and NR; B, D and E are independently CH or N; Y is optionally substituted phenyl, naphthyl, cycloalkyl, cycloalkenyl, a five membered heterocycle containing up to two heteroatoms selected from -O-, -NR2 and -S(O)n, a six membered heterocycle containing up to two heteroatoms selected from the group consisting of -O-, NR2 and -S(O)n or a bicyclic ring system consisting of a five or six membered heterocyclic ring fused to a phenyl ring and containing up to two heteroatoms selected from the group consisting of -O-, -NR2 and -S(O)n; Z1 is -(CH2)pW(CH2)q-, -O(CH2)p CR5R6-, -O(CH2)pW(CH2)q, -OCHR2CHR3- or -SCHR2CHR3-; G is a group: a) -NR7R8; b) an optionally substituted group of formula II which can be optionally fused on adjacent carbon atoms with one or two phenyl rings wherein n is 0, 1 or 2; m is 1, 2 or 3; Z2 is -NH-, -O-, -S- or -CH2- or c) optionally substituted a bicyclic amine containing five to twelve carbon atoms, either bridged or fused or Z1 and G together form a group of formula III W is -CH2-, -CH=CH-, -O-, -NR2-, -S(O)n-, -CO-, -CR2(OH)-, -CONR2-, -NR2CO-, a group of formula IV or -C=C-; R is hydrogen or alkyl; R2 and R3 are independently hydrogen or alkyl; R5 and R6 are independently alkyl or together form a carbocyclic ring; R7 and R8 are independently optionally substituted phenyl, optionally saturated carbocyclic ring, a heterocyclic ring containing up to two heteroatoms selected from -O-, -N- and -S-, H, alkyl or form a 3 to 8 membered nitrogen containing ring with R5 or R6 or a ring formed by R7 and R8 may be optionally fused to a phenyl ring; e is 0, 1 or 2; p is 0,1,2 or 3 and q is 0,1,2 or 3.
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