(2S,4R)-2-[(2,5-difluorobenzylamino)methyl]-4-tritylsulfanylpyrrolidine-1-carboxylic acid isopropyl ester | 844476-74-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (2S,4R)-2-[(2,5-difluorobenzylamino)methyl]-4-tritylsulfanylpyrrolidine-1-carboxylic acid isopropyl ester
• 英文别名: propan-2-yl (2S,4R)-2-[[(2,5-difluorophenyl)methylamino]methyl]-4-tritylsulfanylpyrrolidine-1-carboxylate
• CAS: 844476-74-0
• 化学式: C₃₅H₃₆F₂N₂O₂S
• 分子量: 586.746
• InChiKey: ONUGPOKOHJXLEL-AJQTZOPKSA-N

物化性质

• 沸点：
  651.4±55.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.8
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  66.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,4R)-2-[(2,5-difluorobenzylamino)methyl]-4-tritylsulfanylpyrrolidine-1-carboxylic acid isopropyl ester 在 三乙基硅烷 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以74%的产率得到(2S,4R)-2-[(2,5-difluoro-benzylamino)-methyl]-4-mercapto-pyrrolidine-1-carboxylic acid isopropyl ester
  参考文献：
  名称：

  Endothelin-Converting Enzyme-1 Inhibition and Growth of Human Glioblastoma Cells

  摘要：

  Endothelin-1 (ET-1) is mitogenic and/or antiapoptotic in human cancers, and antagonists to ET-1 receptors are under evaluation for cancer treatment. Inhibition of ET-1 activation by the endothelin-converting enzymes 1(a-d) (ECE-1(a-d); EC 3.4.24.71) represents another approach to block the ET-1 effect in cancer. To evaluate this potential, we synthesized and characterized a series of low nanomolar nonpeptidic thiol-containing ECE-1 inhibitors, and evaluated their effect, as well as the effect of inhibitors for the related metalloproteases neprilysin (NEP; EC 3.4.24.11) and angiotensin-converting enzyme (ACE: EC 3.4.15.1). on human glioblastoma cell growth. Only ECE-1 inhibitors inhibited DNA synthesis by human glioblastoma cells. Exogenous addition of ET-1 or bigET-1 to glioblastoma cells did not counterbalance the growth inhibition elicited by ECE-1 inhibitors, suggesting that ECE-1 inhibitors block the proliferation of human glioblastoma cells most likely via a mechanism not involving extracellular production of ET-1. This class of molecules may thus represent novel therapeutic agents for the potential treatment of human cancer.

  DOI：

  10.1021/jm040857x
• 作为产物：
  描述：

  N-Boc-反式-4-羟基-L-脯氨酸甲酯 在 吡啶 、 四氯化碳 、 4-二甲氨基吡啶 、 lithium aluminium tetrahydride 、 sodium azide 、 potassium tert-butylate 、 水 、 sodium cyanoborohydride 、 N,N-二异丙基乙胺 、 三苯基膦 、 三氟乙酸 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 107.91h， 生成 (2S,4R)-2-[(2,5-difluorobenzylamino)methyl]-4-tritylsulfanylpyrrolidine-1-carboxylic acid isopropyl ester
  参考文献：
  名称：

  Endothelin-Converting Enzyme-1 Inhibition and Growth of Human Glioblastoma Cells

  摘要：

  Endothelin-1 (ET-1) is mitogenic and/or antiapoptotic in human cancers, and antagonists to ET-1 receptors are under evaluation for cancer treatment. Inhibition of ET-1 activation by the endothelin-converting enzymes 1(a-d) (ECE-1(a-d); EC 3.4.24.71) represents another approach to block the ET-1 effect in cancer. To evaluate this potential, we synthesized and characterized a series of low nanomolar nonpeptidic thiol-containing ECE-1 inhibitors, and evaluated their effect, as well as the effect of inhibitors for the related metalloproteases neprilysin (NEP; EC 3.4.24.11) and angiotensin-converting enzyme (ACE: EC 3.4.15.1). on human glioblastoma cell growth. Only ECE-1 inhibitors inhibited DNA synthesis by human glioblastoma cells. Exogenous addition of ET-1 or bigET-1 to glioblastoma cells did not counterbalance the growth inhibition elicited by ECE-1 inhibitors, suggesting that ECE-1 inhibitors block the proliferation of human glioblastoma cells most likely via a mechanism not involving extracellular production of ET-1. This class of molecules may thus represent novel therapeutic agents for the potential treatment of human cancer.

  DOI：

  10.1021/jm040857x

文献信息

• Endothelin-Converting Enzyme-1 Inhibition and Growth of Human Glioblastoma Cells
  作者：Yann Berger、Henrietta Dehmlow、Denise Blum-Kaelin、Eric A. Kitas、Bernd-Michael Löffler、Johannes D. Aebi、Lucienne Juillerat-Jeanneret

  DOI：10.1021/jm040857x

  日期：2005.1.1

  Endothelin-1 (ET-1) is mitogenic and/or antiapoptotic in human cancers, and antagonists to ET-1 receptors are under evaluation for cancer treatment. Inhibition of ET-1 activation by the endothelin-converting enzymes 1(a-d) (ECE-1(a-d); EC 3.4.24.71) represents another approach to block the ET-1 effect in cancer. To evaluate this potential, we synthesized and characterized a series of low nanomolar nonpeptidic thiol-containing ECE-1 inhibitors, and evaluated their effect, as well as the effect of inhibitors for the related metalloproteases neprilysin (NEP; EC 3.4.24.11) and angiotensin-converting enzyme (ACE: EC 3.4.15.1). on human glioblastoma cell growth. Only ECE-1 inhibitors inhibited DNA synthesis by human glioblastoma cells. Exogenous addition of ET-1 or bigET-1 to glioblastoma cells did not counterbalance the growth inhibition elicited by ECE-1 inhibitors, suggesting that ECE-1 inhibitors block the proliferation of human glioblastoma cells most likely via a mechanism not involving extracellular production of ET-1. This class of molecules may thus represent novel therapeutic agents for the potential treatment of human cancer.