2-amino-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid methyl ester hydrochloride

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-amino-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid methyl ester hydrochloride
• 英文别名: Methyl 2-amino-5,6,7,8-tetrahydronaphthalene-1-carboxylate;hydrochloride
• 化学式: C₁₂H₁₅NO₂*ClH
• 分子量: 241.718
• InChiKey: CNWJRBKKAVUCKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.36
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  52.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-amino-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid methyl ester hydrochloride 在 镍 lithium hydroxide 、 氢气 作用下， 以 吡啶 、 甲醇 为溶剂， 20.0~160.0 ℃ 、413.68 kPa 条件下， 反应 5.5h， 生成 2-{[(2-aminophenyl)sulfonyl]amino}-5,6,7,8-tetrahydro-1-naphthalenecarboxylic acid
  参考文献：
  名称：

  Discovery and Optimization of Anthranilic Acid Sulfonamides as Inhibitors of Methionine Aminopeptidase-2:  A Structural Basis for the Reduction of Albumin Binding

  摘要：

  Methionine aminopeptidase-2 (MetAP2) is a novel target for cancer therapy. As part of an effort to discover orally active reversible inhibitors of MetAP2, a series of anthranilic acid sulfonamides with micromolar affinities for human MetAP2 were identified using affinity selection by mass spectrometry (ASMS) screening. These micromolar hits were rapidly improved to nanomolar leads on the basis of insights from protein crystallography; however, the compounds displayed extensive binding to human serum albumin and had limited activity in cellular assays. Modifications based on structural information on the binding of lead compounds to both MetAP2 and domain III of albumin allowed the identification of compounds with significant improvements in both parameters, which showed good cellular activity in both proliferation and methionine processing assays.

  DOI：

  10.1021/jm0601001
• 作为产物：
  描述：

  2-羟基-1-萘酸甲酯 在 palladium on activated charcoal 吡啶 、 盐酸 、 palladium diacetate 、 氢气 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， -20.0~100.0 ℃ 、10.34 MPa 条件下， 反应 7.5h， 生成 2-amino-5,6,7,8-tetrahydronaphthalene-1-carboxylic acid methyl ester hydrochloride
  参考文献：
  名称：

  Discovery and Optimization of Anthranilic Acid Sulfonamides as Inhibitors of Methionine Aminopeptidase-2:  A Structural Basis for the Reduction of Albumin Binding

  摘要：

  Methionine aminopeptidase-2 (MetAP2) is a novel target for cancer therapy. As part of an effort to discover orally active reversible inhibitors of MetAP2, a series of anthranilic acid sulfonamides with micromolar affinities for human MetAP2 were identified using affinity selection by mass spectrometry (ASMS) screening. These micromolar hits were rapidly improved to nanomolar leads on the basis of insights from protein crystallography; however, the compounds displayed extensive binding to human serum albumin and had limited activity in cellular assays. Modifications based on structural information on the binding of lead compounds to both MetAP2 and domain III of albumin allowed the identification of compounds with significant improvements in both parameters, which showed good cellular activity in both proliferation and methionine processing assays.

  DOI：

  10.1021/jm0601001

文献信息

• Discovery and Optimization of Anthranilic Acid Sulfonamides as Inhibitors of Methionine Aminopeptidase-2:  A Structural Basis for the Reduction of Albumin Binding
  作者：George S. Sheppard、Jieyi Wang、Megumi Kawai、Steve D. Fidanze、Nwe Y. BaMaung、Scott A. Erickson、David M. Barnes、Jason S. Tedrow、Lawrence Kolaczkowski、Anil Vasudevan、David C. Park、Gary T. Wang、William J. Sanders、Robert A. Mantei、Fabio Palazzo、Lora Tucker-Garcia、Pingping Lou、Qian Zhang、Chang H. Park、Ki H. Kim、Andrew Petros、Edward Olejniczak、David Nettesheim、Phillip Hajduk、Jack Henkin、Richard Lesniewski、Steven K. Davidsen、Randy L. Bell

  DOI：10.1021/jm0601001

  日期：2006.6.1

  Methionine aminopeptidase-2 (MetAP2) is a novel target for cancer therapy. As part of an effort to discover orally active reversible inhibitors of MetAP2, a series of anthranilic acid sulfonamides with micromolar affinities for human MetAP2 were identified using affinity selection by mass spectrometry (ASMS) screening. These micromolar hits were rapidly improved to nanomolar leads on the basis of insights from protein crystallography; however, the compounds displayed extensive binding to human serum albumin and had limited activity in cellular assays. Modifications based on structural information on the binding of lead compounds to both MetAP2 and domain III of albumin allowed the identification of compounds with significant improvements in both parameters, which showed good cellular activity in both proliferation and methionine processing assays.