发明公开
EP1471066A1 Triaza- and tetraaza-anthracenedione derivates, their preparation and their use as pharmaceuticals
审中-公开
基本信息:
- 专利标题： Triaza- and tetraaza-anthracenedione derivates, their preparation and their use as pharmaceuticals
- 专利标题（中）：Triaza- und Tetraaza-anthrazendionderivate，ihre Herstellung und Verwendung als Pharmazeutika
- 申请号：EP03009286.0 申请日：2003-04-24
- 公开(公告)号：EP1471066A1 公开(公告)日：2004-10-27
- 发明人： Weichert, Andreas , Strobel, Hartmut , Wohlfart, Paulus , Patek, Marcel , Smrcina, Martin , Weichsel, Aleksandra
- 申请人： Aventis Pharma Deutschland GmbH
- 申请人地址： Brüningstrasse 50 65929 Frankfurt am Main DE
- 专利权人： Aventis Pharma Deutschland GmbH
- 当前专利权人： Aventis Pharma Deutschland GmbH
- 当前专利权人地址： Brüningstrasse 50 65929 Frankfurt am Main DE
- 主分类号： C07D471/14
- IPC分类号： C07D471/14 ; C07D487/04 ; A61K31/519 ; A61P9/00
摘要：
The present invention relates to triaza- and tetraaza-anthracenedione derivatives of the formula I,
in which A, B and R 1 to R 5 have the meanings indicated in the claims. The compounds of formula I are valuable pharmacologically active compounds. They are useful in the treatment of various disease states including cardiovascular disorders such as atherosclerosis, thrombosis, coronary artery disease, hypertension and cardiac insufficiency. They upregulate the expression of the enzyme endothelial nitric oxide
(NO) synthase and can be applied in conditions in which an increased expression of said enzyme or an increased NO level or the normalization of a decreased NO level is desired. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.
摘要（中）：
in which A, B and R 1 to R 5 have the meanings indicated in the claims. The compounds of formula I are valuable pharmacologically active compounds. They are useful in the treatment of various disease states including cardiovascular disorders such as atherosclerosis, thrombosis, coronary artery disease, hypertension and cardiac insufficiency. They upregulate the expression of the enzyme endothelial nitric oxide
(NO) synthase and can be applied in conditions in which an increased expression of said enzyme or an increased NO level or the normalization of a decreased NO level is desired. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.
三氮杂和四氮杂蒽并二酮衍生物，其立体异构形式或混合物或盐是新的。 式（I）的三氮杂和四氮杂蒽并二酮衍生物，其立体异构形式或混合物或盐是新的。 [图] A：CR 6或N; B：CR 7或N; R 11-10C烷基，3-8C环烷基，2-10C烯基或2-10C炔基（全部被卤素取代，CN，3-8C环烷基，苯基，联苯基，萘基，茚满基或杂芳基）。 （CH 2）a-苯基， - （CH 2）a-咪唑基或 - （CH 2）a-吡啶基; R 1，R 2， a：0 - 2; R 3 - （CH 2）b-苯基， - （CH 2）b-咪唑基， - （CH-2）b-三唑基， - （CH 2）b-Het或 - （CH 2） b：1 - 4; R 4 -R 7，1-4C烷基，CF 3，1-4C烷氧基，OCF 3，卤素，硝基，CN，-CO-R 10，-NR 8 R 9，-NH-CO-1-4C烷基， -SO 2 - NR 8 R 9，-SO 2-1-4C烷基或-SO 2 - （CH 2）c-苯基; c：0 - 2; R 8和R 9H或1-4C烷基; R 10 OH，1-4C烷氧基或-NR 8 R 9; Het：饱和的5-或6-元单环杂环的残基（含有氮键，通过它与之键合，并另外含有另外的选自N，O和S的环杂原子，并且任选被1-4C烷基或 - （CH 2）d-苯基）; d：0 - 2; 杂芳基：芳族5-10元，单环或双环杂环（含1-4个N，O和S）的残基。 残基苯基，联苯基，萘基，茚满基，杂芳基，吡啶基，咪唑基和三唑基任选被卤素，CN，1-6C烷基，CF 3，1-6C烷氧基或OCF 3取代.A和B不同时为N. 包括（I）的独立索赔。 活动：心血管病。 抗心绞痛; Cardiant; 脑保护; Vasotropic; 溶栓; 抗动脉硬化; 低血压; 呼吸根; Nephrotropic; 抗心律不整; 降血糖; 眼科; 平喘; 抗血管生成; 嗜肝; 骨科。 作用机制：内皮一氧化氮（NO）合酶（eNOS）表达刺激因子。 （4S）-9-（3-（咪唑并）-1-基）丙基）-4-异丙基-6-硝基-2-（4-苯基丁基）-1,2,9,9a四氢2,4a， 如Li等人，激活蛋白激酶Cα和/或ε增加人内皮细胞的转录，测试了9-三氮杂 - 蒽-3,10（4H） - 二酮三氟乙酸（Ia）的eNOS转录活化 一氧化氮合酶基因 药理学。 53（1998）630.（Ia）显示2.2mM的EC 5 0。
IPC结构图谱:
| C | 化学；冶金 |
| --C07 | 有机化学 |
| ----C07D | 杂环化合物 |
| ------C07D471/00 | 在稠环系中含有氮原子作为仅有的杂环原子、其中至少1个环是含有1个氮原子的六元环的杂环化合物，C07D451/00至C07D463/00不包括的 |
| --------C07D471/02 | .在稠环系中含两个杂环 |
| ----------C07D471/14 | ..邻位稠合系 |