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    Aryl pyrimidine derivatives and uses thereof
    8.
    发明授权
    Aryl pyrimidine derivatives and uses thereof 失效
    芳基嘧啶衍生物及其用途

    公开(公告)号：US5958934A

    公开(公告)日：1999-09-28

    申请号：US976418

    申请日：1997-11-21

    申请人： Jacob Berger ,  Lee Allen Flippin ,  Robert Greenhouse ,  Saul Jaime-Figueroa ,  Yanzhou Liu ,  Aubry Kern Miller ,  David George Putman ,  Klaus Kurt Weinhardt ,  Shu-Hai Zhao

    发明人： Jacob Berger ,  Lee Allen Flippin ,  Robert Greenhouse ,  Saul Jaime-Figueroa ,  Yanzhou Liu ,  Aubry Kern Miller ,  David George Putman ,  Klaus Kurt Weinhardt ,  Shu-Hai Zhao

    IPC分类号： A61K31/505 ,  C07D239/42

    CPC分类号： A61K31/505 ,  C07D239/42

    摘要： The aryl pyrimidine derivatives and pharmaceutically acceptable salts and N-oxides thereof, exhibit useful pharmacological properties, including utility as selective 5HT.sub.2B -antagonists. The 5-HT.sub.2B antagonist is a compound of the formula: ##STR1## wherein: R.sup.1 is hydrogen, alkyl, lower alkoxy, hydroxyalkyl, cycloalkyl, cycloalkyl lower alkyl, alkenyl, lower thioalkoxy, halo, fluoroalkyl, --NR.sup.6 R.sup.7, --CO.sub.2 R.sup.8, --O(CH.sub.2).sub.n R.sup.9, or lower alkyl optionally substituted with hydroxy, alkoxy, halo, or aryl; in whichn is 1, 2, or 3;R.sup.6 and R.sup.7 are hydrogen or lower alkyl;R.sup.8 is hydrogen or lower alkyl; andR.sup.9 is hydrogen, lower alkyl, hydroxy, hydroxy lower alkyl, lower alkenyl, or lower alkoxy;R.sup.2 is hydrogen, lower alkyl, lower alkoxy, halo, or lower fluoroalkyl;R.sup.3 is optionally substituted aryl other than pyridyl, thienyl, or furanyl;R.sup.4 is hydrogen, lower alkyl, cycloalkyl, alkenyl, acyl, amino, amido, aryl, --(CH.sub.2).sub.m NR.sup.10 R.sup.11, or lower alkyl optionally substituted by amino, monosubstituted amino, disubstituted amino, hydroxy, carboxy, aryl, lower alkoxy, amido, alkoxy carbonyl, tetrahydrofuran-2-yl, hydroxyalkoxy, or sulfonamido;in whichR.sup.10 and R.sup.11 are hydrogen or lower alkyl; andR.sup.5 is hydrogen or lower alkyl; provided that:(i) when R.sup.3 is naphthyl, indol-1-yl, or 2,3-dihydroindol-1-yl, and R.sup.2, R.sup.4 and R.sup.5 are all hydrogen, R.sup.1 is not methyl;(ii) when R.sup.3 is phenyl or naphthyl, R.sup.1 is not --NR.sup.6 R.sup.7 ;(iii) when R.sup.3 is phenyl, R.sup.2 is not lower alkoxy, and R.sup.1 and R.sup.2 are not halo;(iv) when R.sup.3 is phenyl and R.sup.1 is H, R.sup.2 is not methyl; and(v) when R.sup.3 is 1,2,3,4-tetrahydroquinolinyl, R.sup.4 and R.sup.5 are hydrogen;or a pharmaceutically acceptable salt or N-oxide thereof.

    摘要翻译： 芳基嘧啶衍生物及其药学上可接受的盐和N-氧化物显示出有用的药理学性质，包括作为选择性5HT2B拮抗剂的用途。 5-HT2B拮抗剂是下式的化合物：其中：R 1是氢，烷基，低级烷氧基，羟基烷基，环烷基，环烷基低级烷基，烯基，低级硫代烷氧基，卤素，氟代烷基，-NR 6 R 7，-CO 2 R 8，-O ）n R 9或任选被羟基，烷氧基，卤素或芳基取代的低级烷基; 其中n为1,2或3; R6和R7是氢或低级烷基; R8是氢或低级烷基; 且R 9为氢，低级烷基，羟基，羟基低级烷基，低级烯基或低级烷氧基; R2是氢，低级烷基，低级烷氧基，卤素或低级氟代烷基; R 3是除吡啶基，噻吩基或呋喃基以外的任选取代的芳基; R4是氢，低级烷基，环烷基，烯基，酰基，氨基，酰氨基，芳基， - （CH2）mNR10R11或任选被氨基，单取代的氨基，二取代的氨基，羟基，羧基，芳基，低级烷氧基， 烷氧基羰基，四氢呋喃-2-基，羟基烷氧基或磺酰氨基; 其中R10和R11是氢或低级烷基; R5是氢或低级烷基; 条件是：（i）当R 3是萘基，吲哚-1-基或2,3-二氢吲哚-1-基时，R 2，R 4和R 5都是氢，R 1不是甲基; （ii）当R3是苯基或萘基时，R1不是-NR6R7; （iii）当R3是苯基时，R2不是低级烷氧基，R1和R2不是卤素; （iv）当R3是苯基且R1是H时，R2不是甲基; 和（v）当R 3是1,2,3,4-四氢喹啉基时，R 4和R 5是氢; 或其药学上可接受的盐或N-氧化物。