公开(公告)号：US06376490B1

公开(公告)日：2002-04-23

申请号：US09157806

申请日：1998-09-04

申请人： David John Bull ,  Christopher Lee Carr ,  Michael Jonathan Fray ,  Elisabeth Colette Louise Gautier ,  Charles Eric Mowbray ,  Alan Stobie

发明人： David John Bull ,  Christopher Lee Carr ,  Michael Jonathan Fray ,  Elisabeth Colette Louise Gautier ,  Charles Eric Mowbray ,  Alan Stobie

IPC分类号： A61K315377

CPC分类号： C07D231/12 ,  C07D233/56 ,  C07D249/08 ,  C07D401/04 ,  C07D401/14 ,  C07D403/04 ,  C07D403/14 ,  C07D409/14 ,  C07D413/14 ,  C07D417/14

摘要： The invention provides compounds of the formula (I) or a pharmaceutically acceptable salt thereof, wherein R is a 5-membered ring heteroaryl group containing 3 or 4 nitrogen heteroatoms which is linked to the quinoxalinedione ring by a ring carbon or nitrogen atom said group being optionally benzo-fused and optionally substituted, including in the benzo-fused portion, by 1 or 2 substituents each independently selected from C1-C4 alkyl, C2-C4 alkenyl, C3-C7 cycloalkyl, halo, hydroxy, C1-C4 alkoxy, C3-C7 cycloalkyloxy, —COOH, C1-C4 alkoxycarbonyl, —CONR3R4, —NR3R4, —S(O)p(C1-C4 alkyl), —SO2NR3R4, aryl, aryloxy, aryl(C1-C4)alkoxy, and het, said C1-C4alkyl being optionally substituted by C3-C7 cycloalkyl, halo, hydroxy, C1-C4 alkoxy, halo(C1C4)alkoxy, C3-C7 cycloalkyloxy, C3-C7 cycloalkyl (C1-C4) alkoxy, —COOH, C1-C4 alkoxycarbonyl, —CONR3R4, —NR3R4,—S(O)p(C1-C4 alkyl), —SO2(aryl), —SO2NR3R4 morpholino, aryl, aryloxy, aryl(C1-C4)alkoxy or het, and said C2-C4 alkenyl being optionally substituted by aryl; and R1 and R2 are each independently selected from H, fluoro, chloro, bromo, C1-C4 alkyl and halo(C1-C4)alkyl. The compounds are useful as NDMA receptor antagonists for treating acute neurodegenerative and chronic neurological disorders.

摘要翻译： 本发明提供式（I）化合物或其药学上可接受的盐，其中R是含有3或4个氮杂原子的5元环杂芳基，其通过环碳或氮原子与喹喔啉二酮环连接，所述基团为 任选地苯并稠合并任选被取代的，包括在苯并稠合部分中的1或2个独立地选自C 1 -C 4烷基，C 2 -C 4烯基，C 3 -C 7环烷基，卤素，羟基，C 1 -C 4烷氧基，C 3 -C（C 1 -C 4）烷氧基，-COOH，C 1 -C 4烷氧基羰基，-CONR 3 R 4，-NR 3 R 4，-S（O）p（C 1 -C 4烷基），-SO 2 NR 3 R 4，芳基，芳氧基，芳基（C 1 -C 4）烷氧基， 任选被C 3 -C 7环烷基，卤素，羟基，C 1 -C 4烷氧基，卤代（C 1 -C 4）烷氧基，C 3 -C 7环烷基氧基，C 3 -C 7环烷基（C 1 -C 4）烷氧基，-COOH，C 1 -C 4烷氧基羰基 ，-CONR 3 R 4，-NR 3 R 4，-S（O）p（C 1 -C 4烷基），-SO 2（芳基），-SO 2 NR 3 R 4吗啉代，芳基，芳氧基，芳基（C 1 -C 4）烷氧基或杂原子， 任选地被取代 由芳基 并且R 1和R 2各自独立地选自H，氟，氯，溴，C 1 -C 4烷基和卤代（C 1 -C 4）烷基。 该化合物可用作治疗急性神经变性和慢性神经障碍的NDMA受体拮抗剂。

公开(公告)号：US5783572A

公开(公告)日：1998-07-21

申请号：US793896

申请日：1997-03-12

申请人： Charles Eric Mowbray ,  Alan Stobie ,  Michael Jonathan Fray ,  David John Bull ,  Christopher Lee Carr

发明人： Charles Eric Mowbray ,  Alan Stobie ,  Michael Jonathan Fray ,  David John Bull ,  Christopher Lee Carr

IPC分类号： C07D401/14 ,  A61K31/495 ,  A61K31/535 ,  A61P25/08 ,  A61P25/20 ,  A61P25/28 ,  A61P43/00 ,  C07D403/06 ,  A61K31/55

CPC分类号： C07D403/06

摘要： Compounds of formula (I): ##STR1## and their pharmaceutically acceptable salts, wherein R.sup.1 and R.sub.2 are each independently Cl, Br, CH.sub.3, CH.sub.2 CH.sub.3 or CF.sub.3 ; R.sup.3 is H, CH.sub.3 or CH.sub.2 CH.sub.3 ; and X is a 5-membered heterocyclic group containing up to four nitrogen atoms, attached via a nitrogen atom, the said group being optionally substituted by C.sub.1 -C.sub.6 alkyl or (CH.sub.2).sub.n NR.sup.4 R.sup.5, wherein n is an integer from 1 to 5 and R.sup.4 and R.sup.5 are each independently H, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl or C.sub.1 -C.sub.4 alkyl substituted by phenyl or pyridyl, or R.sup.4 and R.sup.5 are linked to form, together with the nitrogen atom to which attached, a pyrrolidine, piperidine, piperazine, N-(C.sub.1 -C.sub.4 alkyl) piperazine, morpholine or azepine group, or, when X is triazolyl, said group may optionally be benzofused, are NMDA antagonists of value in the treatment of acute neurodegenerative disorders, e.g. arising from stroke or traumatic head injury and in chronic neurological disorders, e.g. senile dementia and Alzheimer's disease.

摘要翻译： PCT No.PCT / EP95 / 03483第 371日期1997年3月12日 102（e）1997年3月12日PCT PCT 1995年9月1日PCT公布。 公开号WO96 / 08485 日本公报（I）的化合物：其中R 1和R 2各自独立地为Cl，Br，CH 3，CH 2 CH 3或CF 3; R3是H，CH3或CH2CH3; 并且X是含有至多四个氮原子的五元杂环基，其通过氮原子连接，所述基团任选被C 1 -C 6烷基或（CH 2）n NR 4 R 5取代，其中n是1至5的整数，R 4 R 5和R 5各自独立地为H，C 1 -C 6烷基，C 3 -C 6环烷基或被苯基或吡啶基取代的C 1 -C 4烷基，或者R 4和R 5与连接的氮原子一起形成吡咯烷，哌啶， 哌嗪，N-（C 1 -C 4烷基）哌嗪，吗啉或吖庚因基，或者当X是三唑基时，所述基团可以任选地被苯并稠合，是治疗急性神经变性疾病的NMDA拮抗剂，例如 由中风或创伤性头部损伤和慢性神经障碍引起的，例如， 老年痴呆和阿尔茨海默病。