methyl 3-(2-oxoindolin-3-yl)propanoate | 133603-37-9

• 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: methyl 3-(2-oxoindolin-3-yl)propanoate
• 英文别名: methyl 3-(2-oxo-1,3-dihydroindol-3-yl)propanoate
• CAS: 133603-37-9
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: JFOMVMVOAXXKKG-UHFFFAOYSA-N

物化性质

• 熔点：
  79-80 °C(Solv: ethyl ether (60-29-7); ligroine (8032-32-4))
• 沸点：
  359.3±35.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  methyl 3-(2-oxoindolin-3-yl)propanoate 在 Selectfluor 作用下， 以 水 、 乙腈 为溶剂， 以25%的产率得到methyl 3-fluorooxindole-3-propionate
  参考文献：
  名称：

  A Novel and Efficient Synthesis of 3-Fluorooxindoles from Indoles Mediated by Selectfluor

  摘要：

  [GRAPHICS]Treatment of several 3-substituted indoles, including derivatives of tryptophan and serotonin, with commercially available Selectfluor in acetonitrile/water furnished 3-substiuted 3-fluorooxindoles in good to high yields. Since 3-fluorooxindoles obtained are sterically similar to both oxindoles and 3-hydroxyoxindoles, they should be useful as probes for investigating the enzymatic mechanism of indole biosynthesis and metabolism.

  DOI：

  10.1021/ol991400y
• 作为产物：
  描述：

  3-吲哚丙酸 在 盐酸 、 二甲基亚砜 作用下， 以 乙醚 为溶剂， 反应 0.5h， 生成 methyl 3-(2-oxoindolin-3-yl)propanoate
  参考文献：
  名称：

  Tyrosine kinase inhibitors. 1. Structure-activity relationships for inhibition of epidermal growth factor receptor tyrosine kinase activity by 2,3-dihydro-2-thioxo-1H-indole-3-alkanoic acids and 2,2'-dithiobis(1H-indole-3-alkanoic acids)

  摘要：

  A series of 2,3-dihydro-2-thioxo-1H-indole-3-alkanoic acids, and their methyl esters were prepared, the majority by oxidation of 1H-indole-3-alkanoic acids (DMSO/HCl), followed by thiation of the corresponding 2,3-dihydro-2-oxo-1H-indole-3-alkanoic acid esters. The monomeric thiones undergo facile and reversible oxidation to the corresponding 2,2'-dithiobis(1H-indole-3-alkanoic acids). The compounds were evaluated for their abilities to inhibit the tyrosine kinase activity of the epidermal growth factor receptor using a native complex contained in plasma membrane vesicles shed from cultured A431 cells, and to inhibit the growth of Swiss 3T3 mouse fibroblast in culture. Enzyme inhibitory activity is dependent on the length of the side chain, with propanoic acid derivatives showing the highest activity. The acids are generally significantly more potent than the corresponding esters, and the disulfides more active than the corresponding monomers. An ability to undergo the thione-thiol tautomerism necessary for dimerization is essential, with 3,3-disubstituted compounds being inactive. Overall, the data suggest that the disulfide is the more active form, with much of the activity of the monomeric thiones being due to varying degrees of conversion to the disulfide during the assay. In the growth inhibition assay, the methyl esters are more potent than their corresponding carboxylic acids, and the dimers are generally more potent than the monomers. The data show these compounds to be a novel and potent class of inhibitors of epidermal growth factor receptor tyrosine kinase activity.

  DOI：

  10.1021/jm00069a003

文献信息

• [EN] D2 ANTAGONISTS, METHODS OF SYNTHESIS AND METHODS OF USE<br/>[FR] ANTAGONISTES D2, PROCÉDÉS DE SYNTHÈSE ET MÉTHODES D'UTILISATION
  申请人：ALTOS THERAPEUTICS LLC

  公开号：WO2011160084A1

  公开（公告）日：2011-12-22

  Provided are D2 or D3 antagonist compounds and pharmaceutical compositions of formula I and pharmaceutically acceptable salts thereof, or isomers thereof, wherein R1, R2 and R3 are as defined herein. The invention further comprises methods for making the compounds of the invention and methods for the treatment of conditions mediated by the dopamine D2 or D3 receptor from the compounds of the invention.

  提供了D2或D3拮抗剂化合物以及公式I和其药学上可接受的盐或异构体的药物组合物，其中R1、R2和R3如本文所定义。该发明还包括制备该发明化合物的方法以及利用该发明化合物治疗由多巴胺D2或D3受体介导的疾病的方法。
• Reductive Coupling of Isatins with α,β-Unsaturated Carbonyl Compounds by Low-Valent Titanium
  作者：Naoki Kise、Yuki Mitsui、Toshihiko Sakurai

  DOI：10.1246/bcsj.20210357

  日期：2022.1.15

  The reductive coupling of isatins with α,β-unsaturated carbonyl compounds by Zn-TiCl4 in THF at 0 °C gave one-to-one coupled products, 3-hydoxy-3-alkyloxindoles. The coupled products obtained from α,β-unsaturated esters were transformed to the corresponding spiro-γ-lactones by refluxing in cat. PPTS/benzene. The two-to-one coupled products, 3,3-bis(2-carbomethoxyethyl)oxindoles, were formed by the

  靛红与 α,β-不饱和羰基化合物在 0 °C 下通过 Zn-TiCl 4在 THF 中的还原偶联得到一对一的偶联产物，3-羟基-3-烷氧基吲哚。由α,β-不饱和酯获得的偶联产物通过在催化剂中回流转化为相应的螺-γ-内酯。PPTS/苯。2:1 偶联产物 3,3-双（2-碳甲氧基乙基）羟吲哚是通过 Zn-TiCl 4在 THF 中在 30 °C 下用丙烯酸甲酯还原靛红形成的。靛红与丙烯酸甲酯还原偶联得到的一对一偶联产物通过Zn-TiCl 4还原为3-(2-甲氧基乙基)羟吲哚在 30 °C 的 THF 中。将 3-(2- 碳甲氧基乙基) 羟吲哚加入丙烯腈中得到 3-(2- 碳甲氧基乙基)-3-(2-氰乙基) 羟吲哚。
• Diastereoselective synthesis of substituted 2,3,4,5-tetrahydro-1<i>H</i>-1-benzazepine-5-carboxylic esters by a tandem reduction-reductive animation reaction
  作者：Richard A. Bunce、Lara B. Johnson、Elizabeth M. Holt

  DOI：10.1002/jhet.5570410413

  日期：2004.7

  diastereoselective synthesis of substituted and unsubstituted 2,3,4,5-tetrahydro-1H-1-benzazepine-5-carboxylic esters has been developed based on the tandem reduction-reductive amination reac tion. Catalytic hydrogenation of a series of 2-(2-nitrophenyl)-5-oxoalkanoic esters initiates a reaction sequence involving (1) reduction of the aromatic nitro group, (2) condensation of the N-hydroxylamino (or amino)

  基于串联还原-还原胺化反应，已经开发了一种有效的非对映选择性合成取代的和未取代的2,3,4,5-四氢-1 H -1-苯并ze庚因-5-羧酸酯。一系列2-（2-硝基苯基）-5-氧代链烷酸酯的催化加氢引发了一个反应序列，涉及（1）芳族硝基的还原，（2）N-羟基氨基（或氨基）氮与侧链的缩合（3）还原七元环亚胺。对于具有C 2烷基和C 5酯基为顺式的产物，产生2-烷基-2,3,4,5-四氢-1 H -1-苯并pine庚因-5-羧酸酯的环化是非对映体选择。在这些反应中，环戊酸酯基团对环状亚胺中间体的还原具有很强的立体定向作用，尽管不如以前的2-烷基-1,2,3,4-四氢喹啉-4-羧酸的闭合反应所观察到的强。酯。非对映选择性的降低归因于（1）酯与亚胺双键之间的距离更大，以及（2）较大环的构象迁移率增加，这两者都减弱了酯的立体定向作用。最后，七元环的形成足够缓慢，以至于在一些反应中与侧链酯基团的反应与杂环的形成竞争。
• D2 ANTAGONISTS, METHODS OF SYNTHESIS AND METHODS OF USE
  申请人：Luehr Gary W.

  公开号：US20120010228A1

  公开（公告）日：2012-01-12

  Provided are D 2 or D 3 antagonist compounds and pharmaceutical compositions of formula I and pharmaceutically acceptable salts thereof, or isomers thereof, wherein R 1 , R 2 and R 3 are as defined herein. The invention further comprises methods for making the compounds of the invention and methods for the treatment of conditions mediated by the dopamine D 2 or D 3 receptor from the compounds of the invention.

  提供了D2或D3拮抗剂化合物及其制备方法，以及公式I的制药组合物及其药学上可接受的盐或同分异构体，其中R1、R2和R3如本文所定义。本发明还涉及制备本发明化合物的方法，以及利用本发明化合物治疗由多巴胺D2或D3受体介导的疾病的方法。
• D2 antagonists, methods of synthesis and methods of use
  申请人：Luehr Gary W.

  公开号：US08691836B2

  公开（公告）日：2014-04-08

  Provided are D2 or D3 antagonist compounds and pharmaceutical compositions of formula I and pharmaceutically acceptable salts thereof, or isomers thereof, wherein R1, R2 and R3 are as defined herein. The invention further comprises methods for making the compounds of the invention and methods for the treatment of conditions mediated by the dopamine D2 or D3 receptor from the compounds of the invention.

  本发明提供了公式I及其药物可接受的盐或异构体的D2或D3拮抗剂化合物和制药组合物，其中R1、R2和R3如本文所定义。本发明还包括制备本发明化合物的方法以及利用本发明化合物治疗由多巴胺D2或D3受体介导的疾病的方法。