dl-8-amino-4,4a,5,6-tetrahydro-2H-benzo(h)-cinnolin-3-one | 103422-66-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: dl-8-amino-4,4a,5,6-tetrahydro-2H-benzo(h)-cinnolin-3-one
• 英文别名: 8-amino-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3[2H]-one；(+-)-8-Amino-4,4a,5,6-tetrahydrobenzo(h)cinnolin-3(2H)-one；8-amino-4,4a,5,6-tetrahydro-2H-benzo[h]cinnolin-3-one
• CAS: 103422-66-8
• 化学式: C₁₂H₁₃N₃O
• 分子量: 215.255
• InChiKey: ZQTAEDPFDWFOBY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  67.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-氯丙酰氯 、 dl-8-amino-4,4a,5,6-tetrahydro-2H-benzo(h)-cinnolin-3-one 以 甲苯 为溶剂， 反应 6.0h， 以72%的产率得到8-[(2-chloropropionyl)amino]-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-one
  参考文献：
  名称：

  取代的苯并[h] cinnolinones和3H-苯并[6,7]环庚[1,2-c]哒嗪酮的合成及生物学评估：降压和抗血栓的5H-茚并[1,2-c]哒嗪酮的较高同系物。

  摘要：

  几个取代的苯并[h]肉桂酮3和3H-苯并[6,7]环庚[1,2-c]哒嗪酮4被设计为5H-茚并[1,2-c]哒嗪酮2的较不刚性的同类物。合成并测试为抗高血压药，正性肌力药，抗血栓药，抗炎药和抗溃疡药。尽管七元环衍生物仅显示出与乙酰水杨酸相当的抗血栓形成特性，但大多数苯并[h]肉桂醇酮显示出显着的抗高血压，正性肌力和抗血栓形成特性。在这方面，发现8-氨基（3b）和8-乙酰氨基（3c）以及3c（11）的4,4a-脱氢类似物具有最有效和最持久的降压活性。特别地，3c的右旋异构体比消旋形式更具活性，心动过速效应更低。

  DOI：

  10.1021/jm00130a009
• 作为产物：
  描述：

  (6-acetamido-1-oxo-1,2,3,4-tetrahydronaphth-2-yl)acetonitrile 在 盐酸 、 一水合肼 作用下， 以 乙醇 为溶剂， 反应 22.0h， 生成 dl-8-amino-4,4a,5,6-tetrahydro-2H-benzo(h)-cinnolin-3-one
  参考文献：
  名称：

  强心剂。4. N-取代的2,4,4a，5-四氢-3H-茚并[1,2-c]哒嗪-3-酮的合成和生物学评价：衍生自CI-930和类似物的刚性结构。

  摘要：

  几种N-取代的3H-茚并[1,2-c]吡啶并酮（1-23）和苯并[h]肉桂酮（24），被设计为5-烷基-4,5-二氢-6的刚性结构修饰合成了[[4-N-取代的苯基] -3（2H）-哒嗪酮（ib-d），并评估了其正性肌力活性。这些三环哒嗪酮中的大多数（1-11、14-15、22-23）表现出有效的正性肌力活性，可与与I相关的相应苯基吡啶并酮类相媲美。

  DOI：

  10.1021/jm00161a003

文献信息

• Tricyclic dihydropyridazinones and pharmaceutical compositions
  申请人：Boehringer Biochemia Robin, S.p.A.

  公开号：US04692447A1

  公开（公告）日：1987-09-08

  The tricyclic dihydropyridazinone derivatives having formula I ##STR1## are endowed with interesting hypotensive, vasodilating, antiaggregant, antithrombotic and cytoprotective properties and are therefore useful in human or veterinary medicine.

  具有以下化学式的三环二氢吡啶并嗪衍生物具有降压、扩血管、抗血小板聚集、抗血栓和细胞保护等有趣的性质，因此在人类或兽医学中具有用途。
• Tricyclic pyridazinone compounds
  申请人：Smith Kline & French Laboratories Limited

  公开号：US04755511A1

  公开（公告）日：1988-07-05

  This invention relates to tricyclic pyridazinone compounds, pharmaceutical compositions containing the compounds, and a method of stimulating cardiac activity in a mammal by administering an effective amount of the compound. A compound of the invention is 7-carboxamido-4,4a-dihydro-4a-methyl-[5H]-indeno[1,2-c]-pyridazin-3[2H]-on e.

  本发明涉及三环吡啶酮化合物、含有该化合物的药物组合物以及通过给哺乳动物施加有效量的该化合物来刺激心脏活动的方法。该发明的一种化合物是7-羧酰胺基-4,4a-二氢-4a-甲基-[5H]-吲哚[1,2-c]-吡啶并[3,2H]-酮。
• Tricyclic dihydropyridazinones and pharmaceutical compositions contaning them
  申请人：BOEHRINGER MANNHEIM ITALIA S.P.A.

  公开号：EP0169443A2

  公开（公告）日：1986-01-29

  The tricyclic dihydropyridazinone derivatives having formula I are endowed with interesting hypotensive, vasodilating, antiaggregant, antithrombotic and cytoprotective properties and are therefore useful in human or veterinary medicine.

  三环二氢哒嗪酮衍生物具有式 I 的三环二氢哒嗪酮衍生物具有有趣的降血压、血管扩张、抗聚集、抗血栓和细胞保护特性，因此可用于人类或兽医领域。
• FUSED PYRIDAZINE COMPOUNDS AND THEIR MEDICINAL USES
  申请人：Yoshitomi Pharmaceutical Industries, Ltd.

  公开号：EP0351435A1

  公开（公告）日：1990-01-24

  Novel fused pyridazine compounds represented by general formula (1) (wherein R1, R2, R3 and R4, which may be the same or different, each represents hydrogen, halogen, hydroxy, nitro, amino, cyano, trifluoromethyl, alkyl, alkoxy or alkanoylamino, one of Ra and Rb represents -O-Y-NR5R6, (wherein R5 and R6, which may be the same or different, each represents hydrogen, alkyl, phenylalkyl or substituted phenylalkyl or, when taken together, R5 and R6 represent a group capable of forming a heterocyclic ring together with the adjacent nitrogen atom, and Y represents straight-chain or branched alkylene optionally having hydroxy group(s) on the chain as the substituent) and the other represents H, or Ra and Rb, which may be the same or different, each represents -0-Y-NR5R6 (wherein R5 and R6 are as defined above), W represents = CH- or = N-, X represents CH2, S, SO, SO2 or 0, and the bond represented by a dotted line represents a single bond or a double bond), pharmaceutically acceptable salts or hydrates thereof and their medicinal uses are disclosed. These compounds have the action of increasing phagocytosis of leucocytes, that of increasing phagocytosis of macrophage, that of restoring the number of leucocytes, an infection protective action, an antitumor action, etc., and can be used for prophylaxis or treatment of diseases including human immunodeficiency.

  通式(1)代表的新型融合哒嗪化合物（其中R1、R2、R3和R4可以相同或不同，各自代表氢、卤素、羟基、硝基、氨基、氰基、三氟甲基、烷基、烷氧基或烷酰氨基，Ra和Rb之一代表-O-Y-NR5R6、(其中 R5 和 R6 可以相同或不同，各自代表氢、烷基、苯基烷基或取代的苯基烷基，或当 R5 和 R6 合在一起时，代表能与相邻氮原子一起形成杂环的基团、Y代表直链或支链亚烷基，可选择在链上具有羟基作为取代基），另一个代表H，或Ra和Rb，它们可以相同或不同，各自代表-0-Y-NR5R6（其中R5和R6如上定义），W代表＝CH-或＝N-，X代表CH2、S、SO、SO2或0，虚线代表的键代表单键或双键），公开了其药学上可接受的盐或水合物及其医药用途。这些化合物具有增加白细胞的吞噬作用、增加巨噬细胞的吞噬作用、恢复白细胞数量的作用、感染保护作用、抗肿瘤作用等，可用于预防或治疗包括人类免疫缺陷在内的疾病。
• Inotropic, vasodilator and low Km, cAMP-selective, cGMP-inhibited phosphodiesterase (PDE III) inhibitory activities of 4a-methyl-4,4a-dihydro-5H-indeno[1,2-c]pyridazin-3(2H)-ones and 4a-methyl-4,4a,5,6-tetrahydrobenzo[h]cinnolin-3(2H)-ones
  作者：SJ Bakewell、WJ Coates、MB Comer、ML Reeves、BH Warrington

  DOI：10.1016/0223-5234(90)90196-a

  日期：1990.11

  Novel 7-substituted-4,4a-dihydro-4a-methyl-5H-indenol[1,2-c]pyridazin-3[2H]-ones and 8-substituted-4a-methylbenzo[h]cinnolin-3[2H]-ones have been synthesized and their PDE III inhibitory, inotropic and vasodilator potencies compared with those of their normethyl analogues and their bicyclic 4,5-dihydro-6-phenylpyridazinone analogues. The structure-activity relationships of the tricyclic pyridazinones differ from those of bicyclic pyridazinones mainly in respect of the effect of introducing the methyl group into the pyridazinone ring. Whilst in the 4,5-dihydro-6-phenylpyridazin-3(2H)-ones, introduction of a 5-methyl group has been widely reported to lead to compounds of significantly greater potency, the novel tricyclic 4a-methylpyridazinones showed similar levels of inotropic, vasodilator and PDE III inhibitory potency to their normethyl analogues. Possible reasons for this difference in behaviour are discussed.