| 主权项 |
1. An opioid receptor antagonist represented by the formula (I): wherein
R is OH, OC1-6 alkyl, C2-8 alkyl, C1-8 haloalkyl, C2-8 alkenyl, C2-8 alkynyl, aryl substituted by one or more groups Y1, CH2-aryl wherein the aryl group is substituted by one or more groups Y1, OCOC1-8 alkyl, COC1-8 alkyl, CONH2, NHCHO, NH2, NHSO2C1-8 alkyl, or NHCO2C1-8 alkyl;Y3 is hydrogen, Br, Cl, F, CF3, NO2, OR8, CO2R9, C1-6 alkyl, NR10R11, NHCOR12, NHCO2R12, CONR13R14 or CH2(CH2)nY2;R1, R2, R3 and R4 are each, independently, one of the following structures: or R1 and R2, R2 and R3 and/or R3 and R4 are bonded together to form a cyclo alkyl group or a bridged heterocyclic ring,wherein at least one of R1, R2, R3 and R4 is other than hydrogen;each Y1 is, independently, hydrogen, OH, Br, Cl, F, CN, CF3, NO2, N3, OR8, CO2R9, C1-6 alkyl, NR10R11, NHCOR12, NHCO2R12, CONR13R14, or CH2(CH2)nY2, or two adjacent Y1 groups form a —O—CH2—O— or —O—CH2CH2—O— group;each Y2 is, independently, hydrogen, CF3, CO2R9, C1-8 alkyl, NR10R11, NHCOR12, NHCO2R12, CONR13R14, CH2OH, CH2OR8, COCH2R9, each n is, independently, 0, 1, 2 or 3;each o is, independently, 0, 1, 2 or 3;each R8, R9, R10, R11, R12, R13 and R14 is, independently, hydrogen, C1-8 alkyl, CH2-aryl wherein the aryl group is substituted by one or more substituents OH, Br, Cl, F, CN, CF3, NO2, N3, C1-6 alkyl, or CH2(CH2)nY2′;each Y2′ is, independently, hydrogen, CF3, or C1-6 alkyl;R5 is —CH2CH2—X—R6, or R6 is C2-8 alkenyl, C1-4 alkyl substituted C4-8 cycloalkyl, C1-4 alkyl substituted C4-8 cycloalkenyl, or thiophene;X is a single bond, —C(O)— or —CH(OR15)—;R15 hydrogen, C1-6 alkyl, —(CH2)q-phenyl or —C(O)—R16;R16 is C1-4 alkyl or —(CH2)q-phenyl;each q is, independently, 1, 2 or 3;R17 is hydrogen, C1-8 alkyl, CO2C1-8 alkylaryl substituted by one or more groups Y1, CH2-aryl substituted by one or more groups Y1, or CO2C1-8 alkyl;R18 is hydrogen, C1-8 alkyl, C2-8 alkenyl, C3-8 alkynyl, CH2CO2C1-8 alkyl, CO2C1-8 alkyl or CH2-aryl substituted by one or more groups Y1;R19 is a group selected from the group consisting of structures (a)-(p): Q is NR21, CH2, O, S, SO, or SO2;each Y4 is, independently, Br, Cl, F, CN, CF3, NO2, N3, OR22, CO2R23, C1-6 alkyl, NR24R25, NHCOR26, NHCO2R27, CONR28R29, or CH2(CH2)nY2,or two adjacent Y4 groups form a —O—CH2—O— or —O—CH2CH2—O— group;p is 0, 1, 2, or 3;R20 is hydrogen, C1-8 alkyl, C2-8 alkenyl, C2-8 alkenyl, CH2OR30, or CH2-aryl substituted by one or more substituents Y1;each R21 is, independently, hydrogen, C1-8 alkyl, CH2-aryl substituted by one or more substituents Y1, NR31R32, NHCOR33, NHCO2R34, CONR35R36, CH2(CH2)nY2, or C(═NH)NR37R38;R30 is hydrogen C1-8 alkyl, C2-8 alkenyl, C2-8 alkenyl, CH2O2C1-8 alkyl, CO2C1-8 alkyl, or CH2-aryl substituted by one or more substituents Y1;R22, R23, R24, R25, R26, R27, R28, R29, R31, R32, R33, R34, R35, R36, R37 and R38 are, independently, hydrogen, C1-8 alkyl, CH2-aryl substituted by one or more substituents OH, Br, Cl, F, CN, CF3, NO2, N3, C1-6 alkyl, or CH2(CH2)nY2′;Z is N or S, wherein when Z is S, there is no R18;X1 is hydrogen, C1-8 alkyl, C2-8 alkenyl, or C2-8 alkynyl;X2 is hydrogen, C1-8 alkyl, C2-8 alkenyl, or C2-8 alkynyl;or X1 and X2 together form ═O, ═S, or ═NH;or a pharmaceutically acceptable salt thereof. |
