(E)-methyl 1-acetyl-3-(ethoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate | 1168152-06-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (E)-methyl 1-acetyl-3-(ethoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate
• 英文别名: methyl (E)-1-acetyl-3-(1-ethoxy-1-phenylmethylidene)-2-oxoindole-6-carboxylate；methyl (E)-1-acetyl-3-[ethoxyphenylmethylene]-2-oxo-1H indole-6-carboxylate；(E)-1-acetyl-3-(ethoxy-phenyl-methylene)-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester；1-acetyl-3-(1-ethoxy-1-phenylmethylene)-6-methoxycarbonyl-2-indolinone；(3E)-1-Acetyl-3-(ethoxyphenylmethylene)-2,3-dihydro-2-oxo-1H-indole-6-carboxylic Acid Methyl Ester；methyl (3E)-1-acetyl-3-[ethoxy(phenyl)methylidene]-2-oxoindole-6-carboxylate
• CAS: 1168152-06-4
• 化学式: C₂₁H₁₉NO₅
• 分子量: 365.386
• InChiKey: NSLGYOTXIPMWNZ-VHEBQXMUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  1-乙酰基-2,3-二氢-2-氧代-1H-吲哚-6-羧酸甲酯	methyl 1-acetyl-2-oxoindoline-6-carboxylate	676326-36-6	C12H11NO4	233.224

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  尼达尼布	nintedanib	656247-17-5	C31H33N5O4	539.634
  ——	methyl 3-(Z)-[1-(4-propylcarbamoyl-phenylamino)-1-phenyl-methylidene]-2-indolinone-6-carboxylate	466694-80-4	C27H25N3O4	455.513
  ——	methyl 3-(Z)-[1-{4-[(4-tert-butyloxycarbonyl-[1,4]diazepan-1-yl)-carbonyl]-phenyl-amino}-1-phenyl-methylidene]-2-indolinone-6-carboxylate	466694-77-9	C34H36N4O6	596.683
  ——	methyl 3-(Z)-[1-{4-[(3-dimethylamino-propyl)-carbamoyl]-phenylamino}-1-phenyl-methylidene]-2-indolinone-6-carboxylate	466694-49-5	C29H30N4O4	498.582
  ——	methyl 3-(Z)-[1-{4-[N-cyclohexyl-N-methyl-carbamoyl]-phenylamino}-1-phenyl-methylidene]-2-indolinone-6-carboxylate	466694-69-9	C31H31N3O4	509.605
  ——	methyl 3-(Z)-[1-{4-[(4-hydroxy-piperidin-1-yl)-carbonyl]-phenylamino}-1-phenyl-methylidene]-2-indolinone-6-carboxylate	466694-73-5	C29H27N3O5	497.55
  ——	methyl 3-(Z)-[1-{3-[(3-dimethylamino-propyl)-carbamoyl]-phenylamino}-1-phenyl-methylidene]-2-indolinone-6-carboxylate	466694-63-3	C29H30N4O4	498.582
  ——	methyl 3-(Z)-[1-{4-[(piperidin-1-yl)-carbonyl]-phenylamino}-1-phenyl-methylidene]-2-indolinone-6-carboxylate	466694-68-8	C29H27N3O4	481.551
  ——	methyl 3-(Z)-[1-{4-[(4-tert-butyloxycarbonyl-piperazin-1-yl)-carbonyl]-phenylamino }-1-phenyl-methylidene]-2-indolinone-6-carboxylate	466694-75-7	C33H34N4O6	582.656
  ——	(Z)-3-({4-[(3-dimethylaminopropyl)-methyl-carbamoyl]-phenylamino}-phenyl-methylene)-2-oxo-2,3-dihydro-1H-indole-6-carboxylic acid methyl ester	466694-50-8	C30H32N4O4	512.608

反应信息

• 作为反应物：
  描述：

  (E)-methyl 1-acetyl-3-(ethoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate 在 甲醇 、 potassium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 乙磺酸尼达尼布
  参考文献：
  名称：

  一种高纯度乙磺酸尼达尼布的制备方法

  摘要：

  本发明公开了一种高纯度乙磺酸尼达尼布的制备方法，所述方法，步骤如下：步骤1，甲苯、SM01、原苯甲酸三乙酯、乙酸酐、DMAP“一锅法”反应，经抽滤即得高纯度中间体INT02；步骤2，INT02、SM02在特定溶剂体系中反应后分离得到中间体INT03；步骤3，INT03、甲醇，KOH反应，得INT04；步骤4，INT04、甲醇，乙磺酸反应，加入甲基叔丁醚，异丙醚，得乙磺酸尼达尼布。

  公开号：

  CN111848490B
• 作为产物：
  描述：

  1-乙酰基-2,3-二氢-2-氧代-1H-吲哚-6-羧酸甲酯 、 原苯甲酸三乙酯 在 乙酸酐 作用下， 反应 6.0h， 生成 (E)-methyl 1-acetyl-3-(ethoxy(phenyl)methylene)-2-oxoindoline-6-carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Indolinones as Triple Angiokinase Inhibitors and the Discovery of a Highly Specific 6-Methoxycarbonyl-Substituted Indolinone (BIBF 1120)

  摘要：

  Inhibition of tumor angiogenesis through blockade of the vascular endothelial growth factor (VEGF) signaling pathway is a new treatment modality in oncology. Preclinical findings suggest that blockade of additional pro-angiogenic kinases, such as Fibroblast and platelet-derived growth factor receptors (FGFR and PDGFR), may improve the efficacy of pharmacological cancer treatment. Indolinones substituted in position 6 were identified as selective inhibitors of VEGF-, PDGF-, and FGF-receptor kinases. In particular, 6-methoxycarbonyl-substituted indolinones showed a highly favorable selectivity profile. Optimization identified potent inhibitors of VEGF-related endothelial cell proliferation with additional efficacy on pericyctes and smooth muscle cells. In contrast, no direct inhibition of tumor cell proliferation was observed. Compounds 2 (BIBF 1000) and 3 (BIBF 1120) are orally available and display encouraging efficacy in in vivo tumor models while being well tolerated. The triple angiokinase inhibitor 3 is currently in phase III clinical trials for the treatment of nonsmall cell lung cancer.

  DOI：

  10.1021/jm900431g

文献信息

• [EN] INDOLINONES COMPOUNDS AND THEIR USE IN THE TREATMENT OF FIBROTIC DISEASES<br/>[FR] COMPOSÉS INDOLINONES ET LEUR UTILISATION DANS LE TRAITEMENT DES MALADIES FIBROTIQUES
  申请人：RESPIVERT LTD

  公开号：WO2017109513A1

  公开（公告）日：2017-06-29

  The present invention relates inter alia to a compound of formula (I) Wherein R1, R2, R3 and Z are as defined in the specification and to compositions comprising the same and to the use of the compounds and to compositions of the compounds in treatment, for example in the treatment of fibrotic diseases or interstitial lung diseases, in particular idiopathic pulmonary fibrosis.

  本发明涉及一种化合物，其化学式为（I），其中R1、R2、R3和Z如规范中所定义，并涉及包含该化合物的组合物，以及该化合物的用途，以及该化合物在治疗中的组合物，例如在治疗纤维化疾病或间质性肺部疾病，特别是特发性肺纤维化方面的用途。
• [EN] 3-Z-[1-(4-(N-((4-METHYL-PIPERAZIN-1-YL)-METHYLCARBONYL)-N-METHYL-AMINO)-ANILINO)-1-PHENYL-METHYLENE]-6-METHOXYCARBONYL-2-INDOLINONE-MONOETHANESULPHONATE AND THE USE THEREOF AS A PHARMACEUTICAL COMPOSITION<br/>[FR] 3-Z-[1-(4-(N-((4-METHYL-PIPERAZIN-1-YL)-METHYLCARBONYL)-N-METHYL-AMINO)-ANILINO)-1-PHENYL-METHYLENE]-6-METHOXYCARBONYL-2-INDOLINONE-MONOETHANESULFONATE ET UTILISATION EN TANT QUE COMPOSITION PHARMACEUTIQUE
  申请人：BOEHRINGER INGELHEIM PHARMA

  公开号：WO2004013099A1

  公开（公告）日：2004-02-12

  The present invention relates to the compound 3-Z-[1-(4-(N-((4-methyl-piperazin-1-yl)-methylcarbonyl)-N-methyl-amino)-anilino)-1-phenyl-methylene]-6-methoxycarbonyl-2-indolinone-monoethanesulphonate of formula (I) and the use thereof as a pharmaceutical composition.

  本发明涉及化合物3-Z-[1-(4-(N-((4-甲基-哌嗪-1-基)-甲基羰基)-N-甲基氨基)-苯氨基)-1-苯基亚甲基]-6-甲氧羰基-2-吲哚酮-单乙磺酸盐的化学式（I），以及其作为药物组合物的用途。
• 取代吲哚满酮衍生物及其用途
  申请人：沈阳药科大学

  公开号：CN106565682B

  公开（公告）日：2019-07-16

  本发明涉及通式I所示的作为酪氨酸激酶抑制剂的吲哚满酮衍生物，及其药学上可接受的盐或异构体，其中R1、R2、R3、R4、R5、R6、R7、n和环A具有在说明书中给出的含义。本发明还涉及所述化合物的制备方法，以及所述化合物在制备预防或治疗纤维变性疾病以及过度增生疾病的药物中的用途。
• Pharmaceutical combination for the treatment of diseases involving cell proliferation, migration or apotosis of myeloma cells, or angiogenesis
  申请人：Boehringer Ingelheim Pharma GmbH & Co.KG

  公开号：EP1473043A1

  公开（公告）日：2004-11-03

  The present invention relates to a pharmaceutical combination for the treatment of diseases which involves cell proliferation, migration or apoptosis of myeloma cells, or angiogenesis. The combination comprises the co-administration of a protein tyrosine kinase receptor antagonist and of a steroid.

  本发明涉及一种药物组合，用于治疗涉及骨髓瘤细胞增殖、迁移或凋亡，或血管生成的疾病。该组合包括蛋白酪氨酸激酶受体拮抗剂和类固醇的联合给药。
• OXINDOLE INHIBITORS OF TYROSINE KINASE
  申请人：Auspex Pharmaceuticals, Inc.

  公开号：US20150284327A1

  公开（公告）日：2015-10-08

  The present invention relates to new oxindole inhibitors of tyrosine kinase, pharmaceutical compositions thereof, and methods of use thereof.

  本发明涉及新的酪氨酸激酶的氧吲哚抑制剂，其药物组成物以及使用方法。