2,3-dihydro-1-methyl-2-oxo-1H-indole-3-butanoic acid | 149287-22-9

• 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: 2,3-dihydro-1-methyl-2-oxo-1H-indole-3-butanoic acid
• 英文别名: 4-(1-Methyl-2-oxo-3-indolinyl)butanoic acid；4-(1-methyl-2-oxo-3H-indol-3-yl)butanoic acid
• CAS: 149287-22-9
• 化学式: C₁₃H₁₅NO₃
• 分子量: 233.267
• InChiKey: RSPGAVRFFFRUKT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,3-dihydro-1-methyl-2-oxo-1H-indole-3-butanoic acid 在 tetraphosphorus decasulfide 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 乙醚 为溶剂， 生成 methyl 4-(1-methyl-2-thioxo-3-indolyl)butanoate
  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
• 作为产物：
  描述：

  methyl 4-(1-methyl-1H-indol-3-yl)butanoic acid ester 在 盐酸 、 二甲基亚砜 作用下， 反应 3.0h， 生成 2,3-dihydro-1-methyl-2-oxo-1H-indole-3-butanoic acid
  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

• 2-thioindoles (selenoindoles) and related disulfides (selenides) which
  申请人：Warner-Lambert

  公开号：US05464861A1

  公开（公告）日：1995-11-07

  2-Thioindoles (2-selenoindoles) and analogous 2-indolinethione (2-indolineselenone) and polysulfide (selenide) compounds, salts thereof, methods of production, intermediates in their production, pharmaceutical compositions containing said compounds, and methods for inhibiting protein kinase dependent disease in a mammal or treating aberrant cell growth in a mammal, using said compositions, are disclosed.

  本发明涉及2-硫代吲哚（2-硒代吲哚）及其类似物2-吲哚硫醇（2-吲哚硒醇）和多硫化物（硒化物）化合物，其盐，制备方法，制备中间体，含有上述化合物的制药组合物以及使用该组合物抑制哺乳动物中的蛋白激酶依赖性疾病或治疗异常细胞生长的方法。
• 2-THIOINDOLES (SELENOINDOLES) AND RELATED DISULFIDES (SELENIDES) WHICH INHIBIT PROTEIN TYROSINE KINASES AND WHICH HAVE ANTITUMOR PROPERTIES
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0654024A1

  公开（公告）日：1995-05-24
• US5464861A
  申请人：——

  公开号：US5464861A

  公开（公告）日：1995-11-07
• US5556874A
  申请人：——

  公开号：US5556874A

  公开（公告）日：1996-09-17
• [EN] 2-THIOINDOLES (SELENOINDOLES) AND RELATED DISULFIDES (SELENIDES) WHICH INHIBIT PROTEIN TYROSINE KINASES AND WHICH HAVE ANTITUMOR PROPERTIES<br/>[FR] 2-THIOINDOLES (SELENOINDOLES) ET DISULFURES ASSOCIES (SELENIURES) INHIBANT LES TYROSINE KINASES ET PRESENTANT DES PROPRIETES ANTITUMORALES
  申请人：——

  公开号：WO1994003427A1

  公开（公告）日：1994-02-17

  [EN] 2-Thioindoles (2-selenoindoles) and analogous 2-indolinethione (2-indolineselenone) and polysulfide (selenide) compounds, salts thereof, methods of production, intermediates in their production, pharmaceutical compositions containing said compounds, and methods for inhibiting protein kinase dependent disease in a mammal or treating aberrant cell growth in a mammal, using said compositions, are disclosed.
  [FR] L'invention concerne des composés de 2-thioindoles (2-sélénoindoles) ainsi que de 2-indolinethione (2-indolinesélénone) et de polysulfure (séléniure) analogues, des sels de ceux-ci, des procédés de production, leurs intermédiaires de production, des compositions pharmaceutiques contenant lesdits composés, ainsi que des procédés d'inhibition de maladies liées à la kinase chez un mammifère, ou de traitement d'une croissance cellulaire aberrante chez un mammifère, à l'aide desdites compositions.