Polycyclic alcaloid-derivatives as NMDA-receptor antagonists
    5.
    发明授权
    Polycyclic alcaloid-derivatives as NMDA-receptor antagonists 失效
    多环类别衍生物作为NMDA-受体拮抗剂

    公开(公告)号:US5990104A

    公开(公告)日:1999-11-23

    申请号:US981935

    申请日:1998-03-25

    摘要: Polycyclic alkaloids of formula (I), wherein R.sub.1 is H, C.sub.1-6 alkyl, or C.sub.6-12 aryl optionally substituted with polar groups; R.sub.2 and R.sub.3 are independently H, OH, C.sub.1-6 alkyl, --C(NH)--NH.sub.2, a positively charged group, or C.sub.7-13 aralkyl optionally substituted with NH.sub.2, OH, C.sub.1-6 alkyl, or halogen; or R.sub.2 and R.sub.3 together form a 5 to 6 member ring optionally incorporating a heteroatom; R.sub.4 is H, C.sub.1-6 alkyl, OR.sub.6, SR.sub.6, or N(R.sub.6).sub.2, wherein each R.sub.6 is independently H, C.sub.1-3 alkyl; X ix O, S, SO, SO.sub.2, or N--R.sub.5, wherein each R.sub.5 is independently H, C.sub.1-6 alkyl, or C.sub.7-13 aralkyl optionally interrupted with one or more heteroatom; n is an integer from 0 to 2; and m is an integer from 0 to 3. These compounds act as antagonists at the ionotropic NMDA (N-methyl-(D)-aspartic acid) receptor. ##STR1##

    摘要翻译: PCT No.CPC / CA96 / 00468 Sec。 371日期:1998年3月25日 102(e)1998年3月25日PCT PCT 1996年7月12日PCT公布。 公开号WO97 / 03929 日期:1997年2月6日式(I)的多环生物碱,其中R 1为H,C 1-6烷基或任选被极性基团取代的C 6-12芳基; R2和R3独立地是H,OH,C1-6烷基,-C(NH)-NH2,带正电荷的基团或任选被NH 2,OH,C 1-6烷基或卤素取代的C 7-13芳烷基; 或R 2和R 3一起形成任选地加入杂原子的5至6元环; R4是H,C1-6烷基,OR6,SR6或N(R6)2,其中每个R6独立地是H,C1-3烷基; X ix O,S,SO,SO 2或N-R 5,其中每个R 5独立地为H,C 1-6烷基或任选被一个或多个杂原子间断的C 7-13芳烷基; n为0〜2的整数; m是0-3的整数。这些化合物在离子型NMDA(N-甲基 - (D) - 天冬氨酸)受体上起拮抗剂的作用。

    Heterocyclic compounds for the treatment of pain and use thereof
    10.
    发明授权
    Heterocyclic compounds for the treatment of pain and use thereof 失效
    用于治疗疼痛的杂环化合物及其用途

    公开(公告)号:US6054474A

    公开(公告)日:2000-04-25

    申请号:US981932

    申请日:1998-03-25

    摘要: Polycyclic alkaloids of formula (I), ##STR1## wherein R.sub.1 is H, C.sub.1-6 alkyl, or C.sub.6-12 aryl optionally substituted with polar groups; R.sub.2 and R.sub.3 are independently H, OH, C.sub.1-6 alkyl, --C(NH)--NH.sub.2, a positively charged group, or C.sub.7-13 aralkyl optionally substituted with NH.sub.2, OH, C.sub.1-6 alkyl, or halogen; or R.sub.2 and R.sub.3 together form a 5 to 6 member ring optionally incorporating a heteroatom; R.sub.4 is H, C.sub.1-6 alkyl, OR.sub.6, SR.sub.6 or N(R.sub.6).sub.2, wherein each R.sub.6 is independently H, C.sub.1-3 alkyl; X is O, S, SO, SO.sub.2, N--R.sub.5, or C--(R.sub.5).sub.2, wherein each R.sub.5 is independently H, C.sub.1-6 alkyl, or C.sub.7-13 aralkyl optionally interrupted with one or more heteroatom; n is an integer from 0 to 2; m is an integer from 0 to 3; with the proviso that when X is CH.sub.2 then R1 is not CH.sub.3, R.sub.2 and R.sub.3 are not both H, R.sub.4 is not OH, m is not 3 and n is not 0. For the treatment of pain and pharmaceutically acceptable compositions comprising those compounds. The compounds of this invention acts as agonists at the opiate receptor.

    摘要翻译: PCT No.PCT / CA96 / 00467 Sec。 371日期:1998年3月25日 102(e)1998年3月25日PCT PCT 1996年7月12日PCT公布。 出版物WO97 / 03978 日期:1997年2月6日式(I)的多环生物碱,其中R 1为H,C 1-6烷基或任选被极性基团取代的C 6-12芳基; R2和R3独立地是H,OH,C1-6烷基,-C(NH)-NH2,带正电荷的基团或任选被NH 2,OH,C 1-6烷基或卤素取代的C 7-13芳烷基; 或R 2和R 3一起形成任选地加入杂原子的5至6元环; R 4是H,C 1-6烷基,OR 6,SR 6或N(R 6)2,其中每个R 6独立地是H,C 1-3烷基; X是O,S,SO,SO 2,N-R 5或C(R 5)2,其中每个R 5独立地是H,C 1-6烷基或任选被一个或多个杂原子中断的C 7-13芳烷基; n为0〜2的整数; m是0至3的整数; 条件是当X是CH 2时,R 1不是CH 3,R 2和R 3都不是H,R 4不是OH,m不是3,n不是0。用于治疗包含这些化合物的疼痛和药学上可接受的组合物。 本发明的化合物作为鸦片剂受体的激动剂。