1-Hydroxy-2,3-bis(3-indolyl)-3-pyrrolin-2,5-dione | 137108-08-8

• 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: 1-Hydroxy-2,3-bis(3-indolyl)-3-pyrrolin-2,5-dione
• 英文别名: 1-hydroxy-3,4-bis(3-indolyl)-2,5-pyrroledione；1H-Pyrrole-2,5-dione, 1-hydroxy-3,4-di-1H-indol-3-yl-；1-hydroxy-3,4-bis(1H-indol-3-yl)pyrrole-2,5-dione
• CAS: 137108-08-8
• 化学式: C₂₀H₁₃N₃O₃
• 分子量: 343.342
• InChiKey: STOYHVQKKWVYFE-UHFFFAOYSA-N

物化性质

• 沸点：
  707.3±70.0 °C(Predicted)
• 密度：
  1.617±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  89.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  吲哚 在 氢氧化钾 、 甲基碘化镁 、 盐酸羟胺 、 potassium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 69.5h， 生成 1-Hydroxy-2,3-bis(3-indolyl)-3-pyrrolin-2,5-dione
  参考文献：
  名称：

  Inhibitors of protein kinase C. 1. 2,3-bisarylmaleimides

  摘要：

  The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described. These 2,3-bisarylznaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a. Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11-mu-M). In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67-mu-M). Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).

  DOI：

  10.1021/jm00079a024

文献信息

• Antimicrobial Activities of Indolocarbazole and Bis-indole Protein Kinase C Inhibitors. II. Substitution on Maleimide Nitrogen with Functional Groups Bearing a Labile Hydrogen.
  作者：ELISABETE RODRIGUES PEREIRA、SERGE FABRE、MARTINE SANCELME、MICHELLE PRUDHOMME、MARYSE RAPP

  DOI：10.7164/antibiotics.48.863

  日期：——

  New compounds, structurally related to the potent protein kinase C inhibitor staurosporine, and substituted on the imide nitrogen with a functional group bearing a labile hydrogen (hydroxymethyl, amino, hydroxy), were synthesized. Their in vitro inhibitory potencies towards protein kinase C and protein kinase A showed that N-hydroxymethyl and N-hydroxy substitution, unlike alkyl substitution, can provide efficient protein kinase C inhibitors. The antimicrobial activities of these new compounds against Streptomyces chartreusis and Streptomyces griseus, Bacillus cereus, Escherichia coli, Candida albicans and Botrytis cinerea were examined. They proved to be inactive against E. coli and two fungi. The results suggest that there is no link between in vitro inhibition of protein kinase C and inhibition of growth and sporulation of the two Streptomyces tested. Unlike indolocarbazole maleimides, bis-indole maleimides are active against the two Streptomyces species.

  新型化合物合成，其结构与强效蛋白激酶C抑制剂星孢菌素相关，并在酰亚胺氮上带有含有活泼氢（羟甲基、氨基、羟基）的功能团进行取代。体外对蛋白激酶C和蛋白激酶A的抑制活性表明，与烷基取代不同，N-羟甲基和N-羟基取代可以提供高效的蛋白激酶C抑制剂。研究了这些新化合物对金色链霉菌、灰色链霉菌、枯草芽孢杆菌、大肠杆菌、白色念珠菌和灰葡萄孢的抗菌活性。它们对大肠杆菌和两种真菌无效。结果表明，体外蛋白激酶C抑制与两种测试链霉菌的生长和孢子形成抑制之间没有联系。与吲哚咔唑马来酰亚胺不同，双吲哚马来酰亚胺对两种链霉菌有活性。
• Inhibitors of protein kinase C. 1. 2,3-bisarylmaleimides
  作者：Peter D. Davis、Christopher H. Hill、Geoffrey Lawton、John S. Nixon、Sandra E. Wilkinson、Steven A. Hurst、Elizabeth Keech、Susan E. Turner

  DOI：10.1021/jm00079a024

  日期：1992.1

  The design and synthesis of a series of novel inhibitors of protein kinase C (PKC) is described. These 2,3-bisarylznaleimides were derived from the structural lead provided by the indolocarbazoles, staurosporine and K252a. Optimum activity required the imide NH, both carbonyl groups, and the olefinic bond of the maleimide ring. 2,3-Bisindolylmaleimides were the most active, and the potency of these was improved by a chloro substituent at the 5-position of one indole ring (compound 28, IC50 0.11-mu-M). In a series of (phenylindolyl)maleimides, nitro compound 74 was most active (IC50 0.67-mu-M). Naphthalene 19 and benzothiophene 21 showed greater than 100-fold selectivity for inhibition of PKC over the closely related cAMP-dependent protein kinase (PKA).