6-phenoxy-1H-indole-2,3-dione | 222036-24-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-phenoxy-1H-indole-2,3-dione
• 英文别名: 6-phenoxyisatin
• CAS: 222036-24-0
• 化学式: C₁₄H₉NO₃
• 分子量: 239.23
• InChiKey: KJRFDFQYKHLWCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-phenoxy-1H-indole-2,3-dione 以87%的产率得到4-[N'-(2-oxo-6-phenoxy-1,2-dihydro-indol-3-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：

  3-苯氧基苯胺 在 盐酸 、 三氟化硼乙醚 、 盐酸羟胺 、 sodium sulfate 作用下， 以 乙醇 为溶剂， 反应 1.5h， 生成 6-phenoxy-1H-indole-2,3-dione
  参考文献：
  名称：

  Oxindole-Based Inhibitors of Cyclin-Dependent Kinase 2 (CDK2):  Design, Synthesis, Enzymatic Activities, and X-ray Crystallographic Analysis

  摘要：

  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.

  DOI：

  10.1021/jm010117d

文献信息

• Inhibition of monoamine oxidase by selected C5- and C6-substituted isatin analogues
  作者：Clarina I. Manley-King、Jacobus J. Bergh、Jacobus P. Petzer

  DOI：10.1016/j.bmc.2010.11.028

  日期：2011.1

  are reversible inhibitors of human monoamine oxidase (MAO) A and B. Both homologues are reported to exhibit selective binding to the MAO-B isoform with (E)-5-styrylisatin being the most potent inhibitor. To further investigate these structure–activity relationships (SAR), in the present study, additional C5- and C6-substituted isatin analogues were synthesized and evaluated as inhibitors of recombinant

  先前的研究表明（E）-5-苯乙烯基和（E）-6-苯乙烯基是人类单胺氧化酶（MAO）A和B的可逆抑制剂。据报道，这两个同系物都与MAO-B同工型具有选择性结合，其中（E）-5-styrylisatin是最有效的抑制剂。为了进一步研究这些结构-活性关系（SAR），在本研究中，合成了另外的C5-和C6-取代的靛红类似物，并评估了它们作为重组人MAO-A和MAO-B的抑制剂。除5-苯基异丁香素外，所有检查的类似物均为选择性MAO-B抑制剂。与相应的C6取代的同系物相比，C5取代的靛红对MAO-B表现出更高的结合亲和力。最有效的MAO-B抑制剂5-（4-苯基丁基）伊斯汀显示的IC 50值为0.66 nM，比（E）-5- styrylisatin的效价高约13倍，比伊斯汀的效价高18,500倍。发现最有效的MAO-A抑制剂是具有IC 50的5-苯基异丁值562nM。结果表明，在C5处被各种取代基取代是
• [EN] SUBSTITUTED OXINDOLE DERIVATIVES AS PROTEIN TYROSINE KINASE AND AS PROTEIN SERINE/THREONINE KINASE INHIBITORS<br/>[FR] DERIVES SUBSTITUES D'OXINDOLE EN TANT QU'INHIBITEURS DE LA TYROSINE KINASE ET DE LA SERINE/THREONINE KINASE
  申请人：GLAXO GROUP LIMITED

  公开号：WO1999015500A1

  公开（公告）日：1999-04-01

  (EN) Compounds of formula (I): wherein X is N, CH, CCF3, or C(C1-12 aliphatic); R4 is sulfonic acid, C1-12 aliphatic-sulfonyl, sulfonyl-C1-12 aliphatic, C1-12 aliphatic-sulfonyl-C1-6 aliphatic, C1-6 aliphatic-amino, R7-sulfonyl, R7-sulfonyl -C1-12 aliphatic, R7-aminosulfonyl, R7-aminosulfonyl-C1-12 aliphatic, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatic, aminosulfonylamino, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl, di-C1-12 aliphatic amino, di-C1-12 aliphatic aminocarbonyl, di-C1-12 aliphatic aminosulfonyl-C1-12 aliphatic, (R8)1-3-Arylamino, (R8)1-3-Arylsulfonyl, (R8)1-3-Aryl-aminosulfonyl, (R8)1-3-Aryl-sulfonylamino, Het-amino, Het-sulfonyl, Het-aminosulfonyl, aminoiminoamino, or aminoiminoaminosulfonyl, R5 is hydrogen; and further wherein R4 and R5 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.(FR) L'invention concerne des composés représentés par la formule (I).X y est N, CH, CCF3, ou C(C1-12 aliphatique); R4 est acide sulfonique, C1-12 aliphatique sulfonyle, sulphonyle C1-12 aliphatique, C1-12 aliphatique sulfonyle-C1-16, aliphatique, C1-16 aliphatique-amino, R7-sulfonyle, R7-sulfonyle -C1-12 aliphatique, R7-aminosulfonyle, R7-aminosulfonyle-C1-12, aliphatique, R7-sulfonylamino, R7-sulfonylamino-C1-12 aliphatique, aminosulfonylamino, di-C1-12 aliphatique amino, di-C1-12 aliphatique aminocarbonyle, di-C1-12 aliphatique aminosulfonyle, di-C1-12 aliphatique amino, di-C1-12 aliphatique aminocarbonyle, di-C1-12 aliphatique aminosulfonyle C1-12 aliphatique, (R8)1-13-arylamino, (R8)1-13-arylsulfonyle, (R8)1-13-arylaminosulfonyle, (R8)1-13-arylsulfonylamino, het-amino, het-sulfonyle, het-aminosulfonyle, aminoiminoamino ou aminoiminoaminosulfonyle; R5 est hydrogène; en outre, R4 et R5 sont éventuellement réunis afin de former un cycle. L'invention concerne également des formulations pharmaceutiques qui renferment ces dérivés et leur utilisation thérapeutique, en particulier dans le traitement de maladies à médiation CDK2, telles que l'alopécie provoquée par la chimiothérapie ou la radiothérapie anticancéreuses.

  化合物的式子为(I)：其中X为N、CH、CCF3或C(C1-12脂肪基)；R4为磺酸、C1-12脂肪基磺酰、磺酰-C1-12脂肪基、C1-12脂肪基磺酰-C1-6脂肪基、C1-6脂肪基氨基、R7磺酰、R7磺酰-C1-12脂肪基、R7氨基磺酰、R7氨基磺酰-C1-12脂肪基、R7磺酰氨基、R7磺酰氨基-C1-12脂肪基、氨基磺酰氨基、双C1-12脂肪基氨基、双C1-12脂肪基氨基羰基、双C1-12脂肪基氨基磺酰、双C1-12脂肪基氨基、双C1-12脂肪基氨基羰基、双C1-12脂肪基氨基磺酰-C1-12脂肪基、(R8)1-3-芳基氨基、(R8)1-3-芳基磺酰、(R8)1-3-芳基氨基磺酰、(R8)1-3-芳基磺酰氨基、杂环氨基、杂环磺酰、杂环氨基磺酰、氨基亚氨基或氨基亚氨基磺酰；R5为氢；并且R4和R5可以选择性地连接形成融合环。其中药物制剂包括它们及其在治疗中的使用，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。
• 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。
• SUBSTITUTED OXINDOLE DERIVATIVES AS PROTEIN TYROSINE KINASE AND AS PROTEIN SERINE/THREONINE KINASE INHIBITORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1009738A1

  公开（公告）日：2000-06-21