2-[2-[[(2S,4R)-4-[(3R,5S)-5-[[(2-methoxycarbonylphenylcarbamoyl)methyl]methylcarbamoyl]-1-(naphthalene-2-sulfonyl)pyrrolidin-3-yldisulfanyl]-1-(naphthalene-2-sulfonyl)pyrrolidine-2-carbonyl]methylamino]acetylamino]benzoic acid methyl ester | 393157-42-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-[2-[[(2S,4R)-4-[(3R,5S)-5-[[(2-methoxycarbonylphenylcarbamoyl)methyl]methylcarbamoyl]-1-(naphthalene-2-sulfonyl)pyrrolidin-3-yldisulfanyl]-1-(naphthalene-2-sulfonyl)pyrrolidine-2-carbonyl]methylamino]acetylamino]benzoic acid methyl ester
• 英文别名: methyl 2-[[2-[[(2S,4R)-4-[[(3R,5S)-5-[[2-(2-methoxycarbonylanilino)-2-oxoethyl]-methylcarbamoyl]-1-naphthalen-2-ylsulfonylpyrrolidin-3-yl]disulfanyl]-1-naphthalen-2-ylsulfonylpyrrolidine-2-carbonyl]-methylamino]acetyl]amino]benzoate
• CAS: 393157-42-1
• 化学式: C₅₂H₅₂N₆O₁₂S₄
• 分子量: 1081.28
• InChiKey: LAGMSEICGRMEAM-WJHUDJMVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.2
• 重原子数：
  74
• 可旋转键数：
  19
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  294
• 氢给体数：
  2
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  2-[2-[[(2S,4R)-4-[(3R,5S)-5-[[(2-methoxycarbonylphenylcarbamoyl)methyl]methylcarbamoyl]-1-(naphthalene-2-sulfonyl)pyrrolidin-3-yldisulfanyl]-1-(naphthalene-2-sulfonyl)pyrrolidine-2-carbonyl]methylamino]acetylamino]benzoic acid methyl ester 在 DL-dithiothreitol 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以91%的产率得到methyl 2-[[2-[methyl-[(2S,4R)-1-naphthalen-2-ylsulfonyl-4-sulfanylpyrrolidine-2-carbonyl]amino]acetyl]amino]benzoate
  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：

  反式-4-羟基-L-脯氨酸甲酯盐酸盐 在 N-甲基吗啉 、 lithium hydroxide 、 O-(2-oxo-1(2H)pyridyl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 碘 、 N,N-二异丙基乙胺 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 2-[2-[[(2S,4R)-4-[(3R,5S)-5-[[(2-methoxycarbonylphenylcarbamoyl)methyl]methylcarbamoyl]-1-(naphthalene-2-sulfonyl)pyrrolidin-3-yldisulfanyl]-1-(naphthalene-2-sulfonyl)pyrrolidine-2-carbonyl]methylamino]acetylamino]benzoic acid methyl 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.