4-[3-[2,5-dihydro-4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-1H-pyrrol-3-yl]-1H-indol-1-yl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester | 170364-25-7

• 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: 4-[3-[2,5-dihydro-4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-1H-pyrrol-3-yl]-1H-indol-1-yl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester
• 英文别名: 4-[3-[4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-indol-1-yl]-piperidine-1-carboxylic acid tert-butyl ester；4-{3-[4-(1-Methyl-1H-indol-3-yl)-2,5-dioxo-2,5-dihydro-1H-pyrrol-3-yl]-indol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester；tert-butyl 4-[3-[4-(1-methylindol-3-yl)-2,5-dioxopyrrol-3-yl]indol-1-yl]piperidine-1-carboxylate
• CAS: 170364-25-7
• 化学式: C₃₁H₃₂N₄O₄
• 分子量: 524.619
• InChiKey: FZXZDHDSQPECTD-UHFFFAOYSA-N

物化性质

• 沸点：
  753.3±60.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  85.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[3-[2,5-dihydro-4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-1H-pyrrol-3-yl]-1H-indol-1-yl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester 在 盐酸 作用下， 以 甲醇 为溶剂， 反应 3.0h， 以57%的产率得到LY 326020
  参考文献：
  名称：

  Synthesis of the tritiated isotopomers of enzastaurin and itsN-des-pyridylmethyl metabolite for use in ADME studies

  摘要：

  Enzastaurin（3-(1-甲基-1H-吲哚-3-基)-4-[1-[1-(2-吡啶基甲基)-4-哌啶基]-1H-吲哚-3-基]-1H-吡咯-2,5-二酮，1）是一种在治疗实体瘤方面具有潜在用途的药物，目前正在进行 II 期临床试验。Enzastaurin 在体外和体内经过代谢会生成多种氧化代谢产物，其中最主要的是 3-(1-甲基-1H-吲哚-3-基)-4-(1-哌啶-4-基-1H-吲哚-3-基)-1H-吡咯-2,5-二酮 (2)。在一项示范研究中，尝试在 Ir[(COD)(Cy3P)pyr]PF6 （Crabtree 催化剂）存在下通过 1 与氘气反应合成 1-[2H]，但没有成功。我们在此报告了一条用于制备氚标记的 2-[3H]并成功将其转化为 1-[3H]的路线。Copyright © 2008 John Wiley & Sons, Ltd. 版权所有。

  DOI：

  10.1002/jlcr.1497
• 作为产物：
  描述：

  4-[3-(2-Amino-2-oxoethyl)-2,3-dihydro-1h-indol-1-yl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester 在 potassium tert-butylate 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 四氢呋喃 为溶剂， 反应 21.0h， 生成 4-[3-[2,5-dihydro-4-(1-methyl-1H-indol-3-yl)-2,5-dioxo-1H-pyrrol-3-yl]-1H-indol-1-yl]-1-piperidinecarboxylic acid 1,1-dimethylethyl ester
  参考文献：
  名称：

  Strategies for the synthesis of N-(azacycloalkyl)bisindolylmaleimides: selective inhibitors of PKCβ

  摘要：

  N-(Azacycloalkyl)bisindolylmaleimides 1 have been identified to be selective inhibitors of PKCbeta. This manuscript will describe the synthetic approaches employed to prepare this class of compounds that resulted in development of efficient methods for preparation of N-(azacycloalkyl) indole 5, indole-3-acetamide 8 and indole-3-glyoxylate ester 4 derivatives. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4020(03)00973-6

文献信息

• Acyclic N-(azacycloalkyl)bisindolylmaleimides: isozyme selective inhibitors of PKCβ
  作者：Margaret M Faul、James R Gillig、Michael R Jirousek、Lawrence M Ballas、Theo Schotten、Astrid Kahl、Michael Mohr

  DOI：10.1016/s0960-894x(03)00286-5

  日期：2003.6

  The synthesis and structure-activity relationship (SAR) trends of a new class of N-(azacycloalkyl)bisindolylmaleimides 1, acyclic derivatives of staurosporine, is described. The representative compound for this series (1e) exhibits an IC50 of 40-50 nM against the human PKCbeta(1) and PKCbeta(2) isozymes and selectively inhibits the PKCbeta isozymes in comparison to other PKC isozymes (alpha, gamma, delta, epsilon, lambda, and eta). The series is also kinase selective for PKC in comparison to other ATP-dependent kinases. A comparison of the PKC isozyme and kinase activity of the series is made to the kinase inhibitor staurosporine. (C) 2003 Elsevier Science Ltd. All rights reserved.
• J. Label. Compd. Radiopharm. 2008, 51, 175-181
  作者：

  DOI：——

  日期：——
• Strategies for the synthesis of N-(azacycloalkyl)bisindolylmaleimides: selective inhibitors of PKCβ
  作者：Margaret M. Faul、John L. Grutsch、Michael E. Kobierski、Michael E. Kopach、Christine A. Krumrich、Michael A. Staszak、Uko Udodong、Jeffrey T. Vicenzi、Kevin A. Sullivan

  DOI：10.1016/s0040-4020(03)00973-6

  日期：2003.9

  N-(Azacycloalkyl)bisindolylmaleimides 1 have been identified to be selective inhibitors of PKCbeta. This manuscript will describe the synthetic approaches employed to prepare this class of compounds that resulted in development of efficient methods for preparation of N-(azacycloalkyl) indole 5, indole-3-acetamide 8 and indole-3-glyoxylate ester 4 derivatives. (C) 2003 Elsevier Ltd. All rights reserved.
• Synthesis of the tritiated isotopomers of enzastaurin and itsN-des-pyridylmethyl metabolite for use in ADME studies
  作者：William J. Wheeler、Dean K. Clodfelter

  DOI：10.1002/jlcr.1497

  日期：2008.3.30

  Enzastaurin (3-(1-methyl-1H-indol-3-yl)-4-[1-[1-(2-pyridinylmethyl)-4-piperidinyl]-1H-indol-3-yl]-1H-pyrrole-2,5-dione, 1), an agent with potential utility in the treatment of solid tumors, is currently in phase II clinical trials. Enzastaurin undergoes metabolism in vitro and in vivo to several products of oxidative metabolism, the major one of which is 3-(1-methyl-1H-indol-3-yl)-4-(1-piperidin-4-yl-1H-indol-3-yl)-1H-pyrrole-2,5-dione (2). In a model study, the attempted synthesis 1-[2H] by reaction of 1 with deuterium gas in the presence of Ir[(COD)(Cy3P)pyr]PF6 (Crabtree's catalyst) was unsuccessful. Alternatively, it was decided to prepare tritiated 2 as both a final product and the starting material for the tritiation of 1. We have reported herein a route that was developed for use in the preparation of tritium-labeled 2-[3H] and its successful conversion to 1-[3H]. Copyright © 2008 John Wiley & Sons, Ltd.

  Enzastaurin（3-(1-甲基-1H-吲哚-3-基)-4-[1-[1-(2-吡啶基甲基)-4-哌啶基]-1H-吲哚-3-基]-1H-吡咯-2,5-二酮，1）是一种在治疗实体瘤方面具有潜在用途的药物，目前正在进行 II 期临床试验。Enzastaurin 在体外和体内经过代谢会生成多种氧化代谢产物，其中最主要的是 3-(1-甲基-1H-吲哚-3-基)-4-(1-哌啶-4-基-1H-吲哚-3-基)-1H-吡咯-2,5-二酮 (2)。在一项示范研究中，尝试在 Ir[(COD)(Cy3P)pyr]PF6 （Crabtree 催化剂）存在下通过 1 与氘气反应合成 1-[2H]，但没有成功。我们在此报告了一条用于制备氚标记的 2-[3H]并成功将其转化为 1-[3H]的路线。Copyright © 2008 John Wiley & Sons, Ltd. 版权所有。