2-bromo-4-(2-(3,4-dihydroxybutyl)-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-1-yl)benzonitrile | 1301177-25-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-bromo-4-(2-(3,4-dihydroxybutyl)-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-1-yl)benzonitrile
• CAS: 1301177-25-2
• 化学式: C₂₂H₂₅BrN₂O₃
• 分子量: 445.356
• InChiKey: BNMWNOYKZFYAKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.86
• 重原子数：
  28.0
• 可旋转键数：
  5.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  86.25
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-bromo-4-(2-(3,4-dihydroxybutyl)-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-1-yl)benzonitrile 在 sodium tetrahydroborate 、 sodium periodate 、 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium azide 、 水 、 双氧水 、 silica gel 、 1-羟基苯并三唑 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 三苯基膦 、 三氟乙酸 、 sodium hydroxide 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 (17S)-5,5,9,17-tetramethyl-7,15-dioxo-2,14,18-triazatetracyclo[17.3.1.02,10.03,8]tricosa-1(23),3(8),9,19,21-pentaene-20-carboxamide
  参考文献：
  名称：

  Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity

  摘要：

  A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. In continuation of our research in this area, macrocyclic amides and lactams were explored to reduce the risk of hERG liabilities. This effort culminated in the discovery of compound 38, which showed a favorable in vitro profile, and efficiently suppressed proliferation of several relevant cell lines. This compound showed prolonged Hsp90-inhibitory activity at least 24 h post-administration, consistent with elevated and prolonged exposure in the tumor. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.112
• 作为产物：
  描述：

  在 四氧化锇 、 N-甲基吗啉氧化物 作用下， 以 叔丁醇 为溶剂， 以70%的产率得到2-bromo-4-(2-(3,4-dihydroxybutyl)-3,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indol-1-yl)benzonitrile
  参考文献：
  名称：

  Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity

  摘要：

  A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. In continuation of our research in this area, macrocyclic amides and lactams were explored to reduce the risk of hERG liabilities. This effort culminated in the discovery of compound 38, which showed a favorable in vitro profile, and efficiently suppressed proliferation of several relevant cell lines. This compound showed prolonged Hsp90-inhibitory activity at least 24 h post-administration, consistent with elevated and prolonged exposure in the tumor. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.112

文献信息

• Design and SAR of macrocyclic Hsp90 inhibitors with increased metabolic stability and potent cell-proliferation activity
  作者：Christoph W. Zapf、Jonathan D. Bloom、Jamie L. McBean、Russell G. Dushin、Thomas Nittoli、Charles Ingalls、Alan G. Sutherland、John P. Sonye、Clark N. Eid、Jennifer Golas、Hao Liu、Frank Boschelli、Yongbo Hu、Erik Vogan、Jeremy I. Levin

  DOI：10.1016/j.bmcl.2011.02.101

  日期：2011.4

  A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. A basic nitrogen within the tether linking the aniline nitrogen atom to a tetrahydroindolone moiety allowed access to compounds with good physical properties. Important structure-activity relationship information was obtained from this series which led to the discovery of a soluble and stable compound which is potent in an Hsp90 binding and cell-proliferation assay. (C) 2011 Elsevier Ltd. All rights reserved.