抗癌医药中间体 | 210644-62-5

• 物质功能分类: 医药中间体 - 杂环化合物 - 吲哚类化合物
• 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
• 中文名称: 抗癌医药中间体
• 英文名称: (Z)-5-[(1,2-dihydro-2-oxo-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrol-3-propanoic acid
• 英文别名: 3-[2,4-dimethyl-5-(2-oxo-1,2-dihydroindol-3-ylidenemethyl)-1H-pyrrol-3-yl]propionic acid；Orantinib；(Z)-3-(2,4-dimethyl-5-((2-oxoindolin-3-ylidene)methyl)-1H-pyrrol-3-yl)propanoic acid；(Z)-3-[(3,5-dimethyl-4-(2-carboxyethyl)-1H-pyrrol-2-yl)-methylidenyl]-indolin-2-one；SU6668；3-[2,4-dimethyl-5-[(Z)-(2-oxo-1H-indol-3-ylidene)methyl]-1H-pyrrol-3-yl]propanoic acid
• CAS: 210644-62-5
• 化学式: C₁₈H₁₈N₂O₃
• 分子量: 310.353
• InChiKey: NHFDRBXTEDBWCZ-ZROIWOOFSA-N

物化性质

• 溶解度：
  DMSO：50 mg/mL（161.11 mM；需要超声）

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  82.2
• 氢给体数：
  3
• 氢受体数：
  3

ADMET

代谢

TSU-68已知的人类代谢物包括TSU-68代谢物2、TSU-68代谢物3和TSU-68代谢物1。

TSU-68 has known human metabolites that include TSU-68 metabolite 2, TSU-68 metabolite 3, and TSU-68 metabolite 1.

来源:NORMAN Suspect List Exchange

安全信息

• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335,H413
• 储存条件：
  室温下应存放在干燥密封的容器中。

上下游信息

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	(5Z,8Z,11Z,14Z,17Z)-N-(2-(3-(2,4-dimethyl-5-((Z)-(2-oxoindolin-3-ylidene)methyl)-1H-pyrrol-3-yl)propanamido)ethyl)icosa-5,8,11,14,17-pentaenamide	——	C40H52N4O3	636.878

反应信息

• 作为反应物：
  描述：

  抗癌医药中间体 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 0.5h， 生成 3-[2,4-Dimethyl-5-(2-oxo-1,2-dihydroindol-3-ylidenemethyl)-1H-pyrrol-3-yl]-propionic acid,sodium salt
  参考文献：
  名称：

  Formulations for pharmaceutical agents ionizable as free acids or free bases

  摘要：

  本发明涉及吲哚酮的配方，这些化合物作为游离酸或游离碱是可离子化的。该配方适用于静脉或口服给药，其中配方包括可离子化的取代吲哚酮和其药用可接受载体。术语“可离子化的取代吲哚酮”包括吡咯取代的2-吲哚酮，除了在化合物的吡咯和2-吲哚酮部分上可选择地被取代外，必须在吡咯基上用一个或多个烃链取代，这些烃链本身被至少一个极性基团取代。如本文所述，这些配方和化合物本身对于治疗蛋白激酶相关疾病是有用的。

  公开号：

  US06878733B1
• 作为产物：
  描述：

  5-(苄氧羰基)-2,4-二甲基-3-吡咯丙酸甲酯 在 palladium on activated charcoal 哌啶 、 sodium hydroxide 、 氢气 、 sodium acetate 作用下， 以 甲醇 、 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 78.0h， 生成 抗癌医药中间体
  参考文献：
  名称：

  Design, Synthesis, and Evaluations of Substituted 3-[(3- or 4-Carboxyethylpyrrol-2-yl)methylidenyl]indolin-2-ones as Inhibitors of VEGF, FGF, and PDGF Receptor Tyrosine Kinases

  摘要：

  Receptor tyrosine kinases (RTKs) have been implicated as therapeutic targets for the treatment of human diseases including cancers, inflammatory diseases, cardiovascular diseases including arterial restenosis, and fibrotic diseases of the lung, liver, and kidney. Three classes of 3-substituted indolin-2-ones containing propionic acid functionality attached to the pyrrole ring at the C-3 position of the core have been identified as catalytic inhibitors of the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) RTKs. Some of the compounds were found to inhibit the tyrosine kinase activity associated with isolated vascular endothelial growth factor receptor 2 (VEGF-R2) [fetal liver tyrosine kinase 1 (Flk-1)/kinase insert domain-containing receptor (KDR)], fibroblast growth factor receptor (FGF-R), and platelet-derived growth factor receptor (PDGF-R) tyrosine kinase with IC50 values at nanomolar level. Thus, compound 1 showed inhibition against VEGF-R2 (Flk-1/KDR) and FGF-R1 tyrosine kinase activity With IC50 values of 20 and 30 nM, respectively, while compound 16f inhibited the PDGF-R tyrosine kinase activity with IC50 value of 10 nM. Structural models and structure-activity relationship analysis of these compounds for the target receptors are discussed. The cellular activities of these compounds were profiled using cellular proliferation assays as measured by bromodeoxyuridine (BrdU) incorporation. Specific and potent inhibition of cell growth was observed for some of these compounds. These data provide evidence that these compounds can be used to inhibit the function of these target receptors.

  DOI：

  10.1021/jm9904295

文献信息

• ISO CA-4 AND ANALOGUES THEREOF AS POTENT CYTOTOXIC AGENTS INHIBITING TUBULINE POLYMERIZATION
  申请人：Alami Mouâd

  公开号：US20100129471A1

  公开（公告）日：2010-05-27

  The invention relates to a compound of the formula (I) in which: R 1 , R 2 and R 3 are independently a methoxy group optionally substituted by one or more fluorine atoms; R 4 is a hydrogen atom; R 5 and R 6 are identical and each represent a hydrogen or fluorine atom; A is a cycle selected from the group including aryl and heteroaryl groups, wherein said groups can be substituted.

  这项发明涉及公式（I）的化合物，其中：R1、R2和R3分别是一个甲氧基基团，该基团可以选择性地被一个或多个氟原子取代；R4是一个氢原子；R5和R6相同，每个代表一个氢或氟原子；A是从包括芳基和杂环基团在内的一组环中选择的，其中这些基团可以被取代。
• Pyrrole substituted 2-indolinone protein kinase inhibitors
  申请人：Sugen, Inc.

  公开号：US06395734B1

  公开（公告）日：2002-05-28

  The present invention relates to novel pyrrole substituted 2-indolinone compounds and physiologically acceptable salts and prodrugs thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.

  本发明涉及新颖的吡咯替代的2-吲哚酮化合物及其生理上可接受的盐和前药，这些化合物调节蛋白激酶的活性，因此预计在预防和治疗蛋白激酶相关的细胞疾病，如癌症方面具有用处。
• DIHYDRO-ISO-CA-4 AND ANALOGUES: POTENT CYTOTOXICS, INHIBITORS OF TUBULIN POLYMERIZATION
  申请人：Alami Mouâd

  公开号：US20110160228A1

  公开（公告）日：2011-06-30

  The present invention relates to compounds of formula (I) below in which: —R 1 and R 3 represent, independently of one another, a methoxy group optionally substituted by one or more fluorine atoms, —R 2 and R 4 represent, independently of one another, a hydrogen atom or a methoxy group optionally substituted by one or more fluorine atoms, —A represents a ring chosen from the group comprising aryl and heteroaryl groups, said ring possibly being substituted by or fused to a heterocycle, —X represents a nitrogen atom or a CH group, and —Z 1 represents a hydrogen atom or a halogen atom, preferably fluorine, and —Z 2 represents a hydrogen atom, a halogen atom, preferably fluorine, a C 1 to C 4 alkyl group, an aryl group or a —CN, —SO 2 NR 12 R 13 , —SO 2 R 9 , —COOR 15 or —COR 15 group, and also to the pharmaceutically acceptable salts thereof, the isomers thereof and the prodrugs thereof.

  本发明涉及以下式（I）的化合物，其中：-R1和R3分别独立地表示一个甲氧基，该甲氧基可以被一个或多个氟原子取代，-R2和R4分别独立地表示一个氢原子或一个甲氧基，该甲氧基可以被一个或多个氟原子取代，-A表示从含有芳基和杂环芳基的群中选择的一个环，该环可能被一个杂环取代或融合，-X表示一个氮原子或一个CH基团，-Z1表示一个氢原子或一个卤原子，优选氟，-Z2表示一个氢原子，一个卤原子，优选氟，一个C1到C4烷基，一个芳基或一个-CN，-SO2NR12R13，-SO2R9，-COOR15或-COR15基团，以及其在药学上可接受的盐，其异构体和其前药。
• Treatment of acute myeloid leukemia with indolinone compounds
  申请人：SUGEN, Inc.

  公开号：US20030130280A1

  公开（公告）日：2003-07-10

  A method of treating acute myeloid leukemia in patient positive for FLT-3-ITD is described. The treatment is accomplished by administration of a compound of Formula I or II as defined herein.

  描述了一种治疗FLT-3-ITD阳性患者急性髓系白血病的方法。该治疗通过给予本文中定义的I或II式化合物来实现。
• Combination therapy for the treatment of cancer
  申请人：Pharmacia Corporation

  公开号：US20030216410A1

  公开（公告）日：2003-11-20

  The present invention relates to methods for treatment or prevention of neoplasia disorders using protein tyrosine kinase inhibitors in combination with cyclooxygenase inhibitors, in particular cyclooxygenase-2 selective inhibitors.

  本发明涉及使用蛋白酪氨酸激酶抑制剂与环氧合酶抑制剂，特别是环氧合酶-2选择性抑制剂，联合治疗或预防肿瘤性疾病的方法。