7-acetamido-4,4-dimethyl-8-nitro-2H,4H-isoquinoline-1,3-dione | 69883-74-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 7-acetamido-4,4-dimethyl-8-nitro-2H,4H-isoquinoline-1,3-dione
• 英文别名: 4,4-dimethyl-7-acetamino-8-nitro-2H,4H-isoquinoline-1,3-dione；N-(4,4-dimethyl-8-nitro-1,3-dioxoisoquinolin-7-yl)acetamide
• CAS: 69883-74-5
• 化学式: C₁₃H₁₃N₃O₅
• 分子量: 291.263
• InChiKey: FGVRNBNMJKTHTE-UHFFFAOYSA-N

物化性质

• 熔点：
  267-268 °C
• 沸点：
  582.4±50.0 °C(Predicted)
• 密度：
  1.396±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-acetamido-4,4-dimethyl-8-nitro-2H,4H-isoquinoline-1,3-dione 在 platinum(IV) oxide 氢气 作用下， 以 甲醇 为溶剂， 70.0 ℃ 、344.75 kPa 条件下， 反应 9.25h， 生成 7,8-diamino-4,4-dimethyl-2H,4H-isoquinoline-1,3-dione
  参考文献：
  名称：

  Discovery of 2-Phenylamino-imidazo[4,5-h]isoquinolin-9-ones:  A New Class of Inhibitors of Lck Kinase

  摘要：

  An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to understand how 1 binds to a related kinase, lick. These results suggested that removing the gem-dimethyl group and flattening the ring would enhance activity. This was realized by converting 1 to the imidazo[4,5-h]isoquinolin-9-one (20), resulting in an 18-fold improvement in potency against lck and a 50-fold increase in potency in a cellular assay.

  DOI：

  10.1021/jm020113o
• 作为产物：
  描述：

  7-amino-4,4-dimethyl-2H,4H-isoquinoline-1,3-dione 在 90percent aq. HNO₃ 作用下， 反应 3.0h， 生成 7-acetamido-4,4-dimethyl-8-nitro-2H,4H-isoquinoline-1,3-dione
  参考文献：
  名称：

  Discovery of 2-Phenylamino-imidazo[4,5-h]isoquinolin-9-ones:  A New Class of Inhibitors of Lck Kinase

  摘要：

  An imidazo[4,5-h]isoquinolin-7,9-dione (1) was identified as an adenosine 5'-triphosphate competitive inhibitor of lck by high throughput screening. Initial structure-activity relationship studies identified the dichlorophenyl ring and the imide NH as important pharmacophores. A binding model was constructed to understand how 1 binds to a related kinase, lick. These results suggested that removing the gem-dimethyl group and flattening the ring would enhance activity. This was realized by converting 1 to the imidazo[4,5-h]isoquinolin-9-one (20), resulting in an 18-fold improvement in potency against lck and a 50-fold increase in potency in a cellular assay.

  DOI：

  10.1021/jm020113o

文献信息

• Heterocyclic compounds useful as inhibitors of tyrosine kinases
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：US06506769B2

  公开（公告）日：2003-01-14

  Disclosed are novel compounds of formula (I): wherein Ar1, Ra, R4, R5, X and Y are defined below, which are useful as inhibitors of certain protein tyrosine kinases and are thus useful for treating diseases associated with such kinases, for example, diseases resulting from inappropriate cell proliferation, which include autoimmune diseases, chronic inflammatory diseases, allergic diseases, transplant rejection and cancer, as well as conditions resulting from cerebral ischemia, such as stroke. Also disclosed are processes for preparing these compounds, novel intermediates useful in these processes and compositions comprising compounds of the formula (I).

  揭示了以下式（I）的新化合物： 其中Ar1、Ra、R4、R5、X和Y的定义如下，这些化合物可用作某些蛋白酪氨酸激酶的抑制剂，因此可用于治疗与这些激酶相关的疾病，例如由于细胞异常增殖导致的疾病，包括自身免疫疾病、慢性炎症性疾病、过敏性疾病、移植排斥和癌症，以及由脑缺血引起的疾病，如中风。还揭示了制备这些化合物的方法，以及在这些方法中有用的新中间体和包含式（I）化合物的组合物。
• Imidazoisoquinoline-diones and salts thereof
  申请人：Boehringer Ingelheim GmbH

  公开号：US04176184A1

  公开（公告）日：1979-11-27

  Compounds of the formula ##STR1## wherein R.sub.1 is lower alkyl; phenyl-lower alkyl; cycloalkyl of 3 to 6 carbon atoms; phenyl; mono- or di-substituted phenyl, where the substituents, which may be identical to or different from each other, are each halogen, hydroxyl, methoxy, methylmercapto, methylsulfinyl, methylsulfonyl or benzyloxy; and A is hydrogen or ##STR2## where R.sub.2 is hydrogen or lower alkyl; R.sub.3 is lower alkyl or dimethoxyphenyl-lower alkyl; or R.sub.2 and R.sub.3, together with each other and the nitrogen atom to which they are attached, are piperidino, morpholino or N'-lower alkyl-piperazino; and n is 2 or 3; and non-toxic, pharmacologically acceptable acid addition salts thereof. The compounds as well as their salts are useful as cardiotonics, hypotensives, antithrombotics and antiarrhythmics.

  式为##STR1##的化合物，其中R.sub.1为较低的烷基；苯基-较低的烷基；3至6个碳原子的环烷基；苯基；单取代或双取代的苯基，取代基可以相同也可以不同，每个取代基都是卤素、羟基、甲氧基、甲硫氧基、甲砜基或苄氧基；A为氢或##STR2##，其中R.sub.2为氢或较低的烷基；R.sub.3为较低的烷基或二甲氧基苯基-较低的烷基；或R.sub.2和R.sub.3，连同它们彼此和它们附着的氮原子，为哌啶基、吗啉基或N'-较低的烷基-哌嗪基；n为2或3；以及其非毒性、药理学上可接受的酸盐。这些化合物及其盐可用作心力衰竭药、降压药、抗血栓药和抗心律失常药。
• HOELCK, J. -P.;KAMPE, W.;MERTENS, A.;MUELLER-BECKMANN, B.;STREIN, K.
  作者：HOELCK, J. -P.、KAMPE, W.、MERTENS, A.、MUELLER-BECKMANN, B.、STREIN, K.

  DOI：——

  日期：——
• HETEROCYCLIC COMPOUNDS USEFUL AS INHIBITORS OF TYROSINE KINASES
  申请人：BOEHRINGER INGELHEIM PHARMACEUTICALS INC.

  公开号：EP1222187A2

  公开（公告）日：2002-07-17
• US4176184A
  申请人：——

  公开号：US4176184A

  公开（公告）日：1979-11-27