(2S,4R)-5-propyl-2-[2-(2,4,5-trifluorobenzyloxymethyl)-4-tritylsulfanylpyrrolidin-1-yl]pyrimidine | 391889-21-7

• 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)-5-propyl-2-[2-(2,4,5-trifluorobenzyloxymethyl)-4-tritylsulfanylpyrrolidin-1-yl]pyrimidine
• 英文别名: (2S,4R)-5-Propyl-2-[2-(2,4,5-trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidin-1-yl]-pyrimidine；5-propyl-2-[(2S,4R)-2-[(2,4,5-trifluorophenyl)methoxymethyl]-4-tritylsulfanylpyrrolidin-1-yl]pyrimidine
• CAS: 391889-21-7
• 化学式: C₃₈H₃₆F₃N₃OS
• 分子量: 639.785
• InChiKey: WABCORJWYZELDM-JHOUSYSJSA-N

物化性质

• 沸点：
  708.7±70.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  46
• 可旋转键数：
  12
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  63.6
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  三氟乙酸 、 (2S,4R)-5-propyl-2-[2-(2,4,5-trifluorobenzyloxymethyl)-4-tritylsulfanylpyrrolidin-1-yl]pyrimidine 在 三异丙基硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 0.33h， 以97%的产率得到(3R,5S)-1-(5-Propyl-pyrimidin-2-yl)-5-(2,4,5-trifluoro-benzyloxymethyl)-pyrrolidine-3-thiol trifluoro-acetate
  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 四氯化碳 、 copper(l) iodide 、 lithium aluminium tetrahydride 、 potassium tert-butylate 、 sodium hydride 、 N,N-二异丙基乙胺 、 三苯基膦 、 三氟乙酸 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 23.41h， 生成 (2S,4R)-5-propyl-2-[2-(2,4,5-trifluorobenzyloxymethyl)-4-tritylsulfanylpyrrolidin-1-yl]pyrimidine
  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

• Pyrrolidine derivatives
  申请人：——

  公开号：US20020055632A1

  公开（公告）日：2002-05-09

  The present invention relates to pyrrolidine derivatives useful as inhibitors of metalloproteases, e.g. zinc proteases, and which are effective in treating disease states associated with vasoconstriction.

  本发明涉及吡咯烷衍生物，可用作金属蛋白酶抑制剂，例如锌蛋白酶，并且对治疗与血管收缩相关的疾病状态有效。
• US6660738B2
  申请人：——

  公开号：US6660738B2

  公开（公告）日：2003-12-09
• 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.