(2-oxo-1,2-dihydro-benz[cd]indol-1-yl)-acetic acid ethyl ester | 85386-79-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2-oxo-1,2-dihydro-benz[cd]indol-1-yl)-acetic acid ethyl ester
• 英文别名: (2-Oxo-1,2-dihydro-benz[cd]indol-1-yl)-essigsaeure-aethylester；2-oxo-benz[cd]indole-1(2H)-acetic acid, ethyl ester；2-oxo-benz[cd]indole-1(2H)acetic acid, ethyl ester；ethyl 2-(2-oxobenzo[cd]indol-1-yl)acetate
• CAS: 85386-79-4
• 化学式: C₁₅H₁₃NO₃
• mdl: MFCD12636360
• 分子量: 255.273
• InChiKey: MABRXSSTDDUIEU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2-oxo-1,2-dihydro-benz[cd]indol-1-yl)-acetic acid ethyl ester 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 生成 2-(2-oxobenzo[cd]indol-1(2H)-yl)acetic acid
  参考文献：
  名称：

  Synthesis and in vitro aldose reductase inhibitory activity of compounds containing an N-acylglycine moiety

  摘要：

  A number of N-benzoylglycines (6), N-acetyl-N-phenylglycines (7), N-benzoyl-N-phenylglycines (8), and tricyclic N-acetic acids (9-12) were synthesized as analogues of the N-acylglycine-containing aldose reductase inhibitors alrestatin and 2-oxoquinoline-1-acetic acid. Derivatives of 6, which represent ring-simplified analogues of alrestatin, are very weak inhibitors of aldose reductase obtained from rat lens, producing 50% inhibition only at concentrations exceeding 100 microM. Compounds of series 7 were designed as ring-opened analogues of the 2-oxoquinolines. While these derivatives are more potent than compounds of series 6 (IC50S of 6-80 microM), they are less active than the corresponding 2-oxoquinolines. Analogues of series 8 were designed as hybrid structures of both alrestatin and the 2-oxoquinoline-1-acetic acids. These compounds are substantially more potent than compounds of series 6 and 7 and display inhibitory activities comparable to or greater than alrestatin or the 2-oxoquinolines (IC50S of 0.1-10 microM). Of the rigid analogues of 8, the most potent derivative is benzoxindole (12) with an IC50 of 0.67 microM, suggesting that fusion of the two aromatic rings of 8 in a coplanar conformation may optimize affinity for aldose reductase in this series.

  DOI：

  10.1021/jm00125a017
• 作为产物：
  描述：

  N-羟基-1,8-萘二甲酰亚胺 在 potassium carbonate 、 potassium iodide 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (2-oxo-1,2-dihydro-benz[cd]indol-1-yl)-acetic acid ethyl ester
  参考文献：
  名称：

  Synthesis and Biological Evaluation of a Benz[cd]indol-2(1H)-one Derivatives

  摘要：

  对640万种化合物的虚拟筛选与非洲爪蟾Aurora B激酶的结构进行比对，确定了1-(n-丙基)-6-[2-(羧酸)四氢吡咯-1-基]磺酰基苯并[cd]吲哚-2(1H)-酮1作为潜在的领先化合物。随后，合成了一系列新型的苯并[cd]吲哚-2(1H)-酮衍生物，并评估其作为Aurora B激酶抑制剂的活性。合成化合物的结构通过1H NMR、红外光谱、质谱和元素分析得到确认。这些化合物通过光谱法进行体外酶活性测定。其中，化合物7e对Aurora B激酶表现出强效的抗肿瘤活性。

  DOI：

  10.14233/ajchem.2014.16729

文献信息

• 2-Thioxobenz[cd]indole-1(2H)-acetic acid derivatives
  申请人：Ayerst, McKenna & Harrison Inc.

  公开号：US04369188A1

  公开（公告）日：1983-01-18

  Herein are disclosed compounds of the formula ##STR1## in which R.sup.1 is hydrogen, lower alkyl or --(CH.sub.2).sub.m --NR.sup.4 R.sup.5 wherein m is an integer from 2 to 6 and R.sup.4 and R.sup.5 each is hydrogen or lower alkyl; R.sup.2 is hydrogen, bromo or chloro; and R.sup.3 is hydrogen or halo; with the requirement that when R.sup.2 is bromo or chloro, then R.sup.3 is bromo or chloro or a therapeutically acceptable salt thereof. The compounds inhibit lens aldose reductase in a diabetic mammal.

  本文披露具有以下式子的化合物：##STR1## 其中R.sup.1为氢、低碳基或--(CH.sub.2).sub.m --NR.sup.4 R.sup.5，其中m为2到6的整数，R.sup.4和R.sup.5各为氢或低碳基；R.sup.2为氢、溴或氯；R.sup.3为氢或卤素；要求当R.sup.2为溴或氯时，R.sup.3为溴或氯或其治疗上可接受的盐。这些化合物在糖尿病哺乳动物中抑制晶状体醛还原酶。
• Schroeter; Roessler, Chemische Berichte, 1902, vol. 35, p. 4224
  作者：Schroeter、Roessler

  DOI：——

  日期：——
• Synthesis and in vitro aldose reductase inhibitory activity of compounds containing an N-acylglycine moiety
  作者：Jack DeRuiter、Blake E. Swearingen、Vinay Wandrekar、Charles A. Mayfield

  DOI：10.1021/jm00125a017

  日期：1989.5

  A number of N-benzoylglycines (6), N-acetyl-N-phenylglycines (7), N-benzoyl-N-phenylglycines (8), and tricyclic N-acetic acids (9-12) were synthesized as analogues of the N-acylglycine-containing aldose reductase inhibitors alrestatin and 2-oxoquinoline-1-acetic acid. Derivatives of 6, which represent ring-simplified analogues of alrestatin, are very weak inhibitors of aldose reductase obtained from rat lens, producing 50% inhibition only at concentrations exceeding 100 microM. Compounds of series 7 were designed as ring-opened analogues of the 2-oxoquinolines. While these derivatives are more potent than compounds of series 6 (IC50S of 6-80 microM), they are less active than the corresponding 2-oxoquinolines. Analogues of series 8 were designed as hybrid structures of both alrestatin and the 2-oxoquinoline-1-acetic acids. These compounds are substantially more potent than compounds of series 6 and 7 and display inhibitory activities comparable to or greater than alrestatin or the 2-oxoquinolines (IC50S of 0.1-10 microM). Of the rigid analogues of 8, the most potent derivative is benzoxindole (12) with an IC50 of 0.67 microM, suggesting that fusion of the two aromatic rings of 8 in a coplanar conformation may optimize affinity for aldose reductase in this series.
• Synthesis and Biological Evaluation of a Benz[cd]indol-2(1H)-one Derivatives
  作者：Jing Nie、Dan-Dan Dong、Yan Zhang、Tai-Yi Wang、Wei Liu、Shou-Zhi Yi

  DOI：10.14233/ajchem.2014.16729

  日期：——

  Virtual screening of a library of 6.4 million compounds versus the structure of Xenopus Laevis Aurora B kinase identified 1-(n-propyl)-6-[2-(carboxyl)tetrahydropyrrol-1-yl]sulfonyl-benzo[cd]indol-2(1H)-one 1 as a possible lead compound. Then, a novel series of benz[cd]indol-2(1H)-one derivatives were synthesized and evaluated as Aurora B kinase inhibitors. The structures of the synthetic compounds were confirmed by 1H NMR, IR, mass spectrometry and elemental analysis. These compounds were evaluated by in vitro enzyme assay using spectrophotometry. Among them, compound 7e displayed potent antitumor activity against Aurora B kinase.

  对640万种化合物的虚拟筛选与非洲爪蟾Aurora B激酶的结构进行比对，确定了1-(n-丙基)-6-[2-(羧酸)四氢吡咯-1-基]磺酰基苯并[cd]吲哚-2(1H)-酮1作为潜在的领先化合物。随后，合成了一系列新型的苯并[cd]吲哚-2(1H)-酮衍生物，并评估其作为Aurora B激酶抑制剂的活性。合成化合物的结构通过1H NMR、红外光谱、质谱和元素分析得到确认。这些化合物通过光谱法进行体外酶活性测定。其中，化合物7e对Aurora B激酶表现出强效的抗肿瘤活性。