1,6-dihydro-1,2,3,6-tetraaza-as-indacene-7,8-dione | 222036-65-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并三唑类
• 英文名称: 1,6-dihydro-1,2,3,6-tetraaza-as-indacene-7,8-dione
• 英文别名: 1,6-dihydro[1,2,3]triazolo[4,5-e]indole-7,8-dione；2,6-dihydropyrrolo[3,2-e]benzotriazole-7,8-dione
• CAS: 222036-65-9
• 化学式: C₈H₄N₄O₂
• 分子量: 188.145
• InChiKey: DYWLWPUEYQKEHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,6-dihydro-1,2,3,6-tetraaza-as-indacene-7,8-dione 生成 (E)-4-[2-(7-oxo-6,7-dihydro[1,2,3]triazolo[4,5-e]indol-8(3H)-ylidene)-hydrazino]benzenesulfonamide
  参考文献：
  名称：

  Substituted oxidole derivatives as protein tyrosine and as protein serine/threonine kinase inhibitors

  摘要：

  本发明总体上涉及新颖的取代吲哚化合物和组合物。这类化合物和组合物作为治疗药物，在治疗通过抑制或拮抗蛋白激酶激活的信号通路而缓解的疾病或状况方面具有效用。特别是，本发明涉及一系列取代吲哚化合物，这些化合物表现出蛋白酪氨酸激酶和蛋白丝氨酸/苏氨酸激酶的抑制作用，并且可用于通过抑制这些激酶来抑制肿瘤生长，以及保护接受化疗的患者免受化疗引起的脱发。

  公开号：

  US06369086B1
• 作为产物：
  描述：

  双(1H-苯并三唑-5-胺)硫酸盐 以6%的产率得到1,6-dihydro-1,2,3,6-tetraaza-as-indacene-7,8-dione
  参考文献：
  名称：

  3-(anilinomethylene) oxindoles

  摘要：

  本发明一般涉及新型胺取代的噁二酮化合物和组合物。这些化合物和组合物作为药理学药剂在治疗由于一般蛋白激酶激活的信号通路的抑制或拮抗而减轻的疾病或症状方面具有实用性，特别是在涉及异常细胞增殖的病理过程中，如肿瘤生长。具体而言，本发明涉及一系列取代的噁二酮化合物，其表现出蛋白酪氨酸激酶和蛋白丝氨酸/苏氨酸激酶抑制作用，并且在通过抑制与肿瘤相关的血管生成抑制肿瘤生长方面是有用的。

  公开号：

  US06350747B1

文献信息

• Substituted oxindole derivatives as protein tyrosine kinase and as protein serine/threonine kinase inhibitors
  申请人：——

  公开号：US20030004351A1

  公开（公告）日：2003-01-02

  Compounds of formula (I): wherein X is N, CH, CCF 3 , or C(C 1-12 aliphatic); R 4 is sulfonic acid, C 1-12 aliphatic-sulfonyl, sulfonyl-C 1-12 aliphatic, C 1-12 aliphatic-sulfonyl-C 1-6 aliphatic, C 1-6 aliphatic-amino, R 7 -sulfonyl, R 7 sulfonyl-C 1-12 aliphatic, R 7 -aminosulfonyl, R 7 -aminosulfonyl-C 1-12 aliphatic, R 7 -sulfonylamino, R 7 -sulfonylamino-C 1-12 aliphatic, aminosulfonylamino, di-C 1-12 aliphatic amino, di-C 1-12 aliphatic aminocarbonyl, di-Cl 1-12 aliphatic aminosulfonyl, di-C 1-12 aliphatic amino, di-C 1-12 aliphatic aminocarbonyl, di-C 1-12 aliphatic aminosulfonyl-C 1-12 aliphatic, (R 8 ) 1-3 -Arylamino, (R 8 ) 1-3 -Arylsulfonyl, (R 8 ) 1-3 -Aryl-aminosulfonyl, (R 8 ) 1-3 -Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R 5 is hydmogen; and further wherein R 4 and R 5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by cancer chemotherapy or radiotherapy.

  式(I)的化合物：其中X为N、CH、CCF3或C（C1-12脂肪族）；R4为磺酸、C1-12脂肪族磺酰基、磺酰-C1-12脂肪族、C1-12脂肪族-磺酰基-C1-6脂肪族、C1-6脂肪族-氨基、R7-磺酰基、R7-磺酰基-C1-12脂肪族、R7-氨基磺酰基、R7-氨基磺酰基-C1-12脂肪族、R7-磺酰胺基、R7-磺酰胺基-C1-12脂肪族、氨基磺酰胺基、二C1-12脂肪族氨基、二C1-12脂肪族氨基甲酰基、二C1-12脂肪族氨基磺酰基、二C1-12脂肪族氨基、二C1-12脂肪族氨基甲酰基、二C1-12脂肪族氨基磺酰基-C1-12脂肪族、（R8）1-3-芳基氨基、（R8）1-3-芳基磺酰基、（R8）1-3-芳基氨基磺酰基、（R8）1-3-芳基磺酰胺基、Het-氨基、Het-磺酰基、Het-氨基磺酰基、氨基亚胺基或氨基亚胺基磺酰基；R5为氢；进一步地，其中R4和R5可选地结合形成融合环，以及包含它们的制药配方和它们在治疗中的用途，特别是在治疗CDK2活性介导的疾病方面，如由癌症化疗或放疗引起的脱发。
• Substituted oxindole derivatives as protein tyrosine and as protein serine/threonine kinase inhibitors and compositions and methods of treating chemotherapy and radiation therapy side effects
  申请人：——

  公开号：US20030069430A1

  公开（公告）日：2003-04-10

  Compounds of formula (I): wherein X is N, CH, CCF 3 , or C(C 1-12 aliphatic); R 4 is sulfonic acid, C 1-12 aliphatic-sulfonyl, sulfonyl-C 1-12 aliphatic, C 1-12 aliphatic-sulfonyl-C 1-6 aliphatic, C 1-6 aliphatic-amino, R 7 -sulfonyl, R 7 sulfonyl-C 1-12 aliphatic, R 7 -aminosulfonyl, R 7 aminosulfonyl-C 1-12 aliphatic, R 7 -sulfonylamino, R 7 -sulfonylamino-C 1-12 aliphatic, aminosulfonylamino, di-C 1-12 aliphatic amino, di-C 1-12 aliphatic aminocarbonyl, di-C 1-12 aliphatic aminosulfonyl, di-C 1-12 aliphatic amino, di-C 1-12 aliphatic aminocarbonyl, di-C 1-12 aliphatic aminosulfonyl-C 1-12 aliphatic, (R 8 ) 1-3 -Arylamino, (R 8 ) 1-3 -Arylsulfonyl, (R 8 ) 1-3 -Aryl-aminosulfonyl, (R 8 ) 1-3 -Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R 5 is hydrogen; and further wherein R 4 and R 5 are optionally joined to form a fused ring, pharmaceutical formulations comprising them and their use in therapy, especially in the treatment of diseases mediated by CDK2 activity, such as alopecia induced by cancer chemotherapy or radiotherapy.

  化合物的公式（I）：其中X为N，CH，CCF3或C（C1-12脂肪族）; R4为磺酸，C1-12脂肪族磺酰基，磺酰基-C1-12脂肪族，C1-12脂肪族磺酰基-C1-6脂肪族，C1-6脂肪族氨基，R7-磺酰基，R7磺酰基-C1-12脂肪族，R7-氨基磺酰基，R7氨基磺酰基-C1-12脂肪族，R7-磺酰胺基，R7-磺酰胺基-C1-12脂肪族，氨基磺酰胺基，二C1-12脂肪族氨基，二C1-12脂肪族氨基甲酰基，二C1-12脂肪族氨基磺酰基，二C1-12脂肪族氨基，二C1-12脂肪族氨基甲酰基，二C1-12脂肪族氨基磺酰基-C1-12脂肪族，（R8）1-3-芳基氨基，（R8）1-3-芳基磺酰基，（R8）1-3-芳基氨基磺酰基，（R8）1-3-芳基磺酰胺基，Het-氨基，Het-磺酰基，Het-氨基磺酰基，氨基亚氨基，或氨基亚氨基磺酰基，R5为氢; 进一步地，其中R4和R5可选择地连接以形成融合环，包括它们的制药配方以及它们在治疗中的应用，特别是在CDK2活性介导的疾病治疗中，例如由癌症化疗或放疗引起的脱发。
• 3-(Anilinomethylene)oxindoles
  申请人：——

  公开号：US20020099071A1

  公开（公告）日：2002-07-25

  1 Compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, A, D, X, Y and Z have the meaning as defined in the claims exhibit protein tyrosine kinase and protein serin/threonine kinase inhibitory activity.

  公式（I）中的化合物，其中R1，R2，R3，R4，R5，R6，R7，R8，A，D，X，Y和Z的含义如权利要求中所定义，具有蛋白酪氨酸激酶和蛋白丝氨酸/苏氨酸激酶抑制活性。
• Compounds
  申请人：——

  公开号：US20040191210A1

  公开（公告）日：2004-09-30

  1 Compounds of formula (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, A, D, X, Y and Z have the meaning as defined in the claims exhibit protein tyrosine kinase and protein serin/threonine kinase inhibitory activity.

  化合物式（I）其中R1，R2，R3，R4，R5，R6，R7，R8，A，D，X，Y和Z的含义如权利要求所定义，表现出蛋白酪氨酸激酶和蛋白质丝氨酸/苏氨酸激酶抑制活性。
• Oxindole-Based Inhibitors of Cyclin-Dependent Kinase 2 (CDK2):  Design, Synthesis, Enzymatic Activities, and X-ray Crystallographic Analysis
  作者：H. Neal Bramson、John Corona、Stephen T. Davis、Scott H. Dickerson、Mark Edelstein、Stephen V. Frye、Robert T. Gampe、Phil A. Harris、Anne Hassell、William D. Holmes、Robert N. Hunter、Karen E. Lackey、Brett Lovejoy、Michael J. Luzzio、Val Montana、Warren J. Rocque、David Rusnak、Lisa Shewchuk、James M. Veal、Duncan H. Walker、Lee F. Kuyper

  DOI：10.1021/jm010117d

  日期：2001.12.1

  Two closely related classes of oxindole-based compounds, 1H-indole-2,3-dione 3-phenylhydrazones and 3-(anilinomethylene)-1,3-dihydro-2H-indol-2-ones, were shown to potently inhibit cyclin-dependent kinase 2 (CDK2). The initial lead compound was prepared as a homologue of the 3-benzylidene-1,3-dihydro-2H-indol-2-one class of kinase inhibitor. Crystallographic analysis of the lead compound bound to CDK2 provided the basis for analogue design. A semiautomated method of ligand docking was used to select compounds for synthesis, and a number of compounds with low nanomolar inhibitory activity versus CDK2 were identified. Enzyme binding determinants for several analogues were evaluated by X-ray crystallography. Compounds in this series inhibited CDK2 with a potency similar to 10-fold greater than that for CDK1. Members of this class of inhibitor cause an arrest of the cell cycle and have shown potential utility in the prevention of chemotherapy-induced alopecia.