(2S,4R)-(2,5-difluorobenzyl)-[1-(5-propylpyrimidin-2-yl)-4-tritylsulfanylpyrrolidin-2-ylmethyl]amine | 391889-57-9

• 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)-(2,5-difluorobenzyl)-[1-(5-propylpyrimidin-2-yl)-4-tritylsulfanylpyrrolidin-2-ylmethyl]amine
• 英文别名: (2S,4R)-(2,5-Difluoro-benzyl)-[1-(5-propyl-pyrimidin-2-yl)-4-tritylsulfanyl-pyrrolidin-2-ylmethyl]-amine；N-[(2,5-difluorophenyl)methyl]-1-[(2S,4R)-1-(5-propylpyrimidin-2-yl)-4-tritylsulfanylpyrrolidin-2-yl]methanamine
• CAS: 391889-57-9
• 化学式: C₃₈H₃₈F₂N₄S
• 分子量: 620.809
• InChiKey: BTGNZNGAPDNTAX-OIDHKYIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.8
• 重原子数：
  45
• 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：
  66.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,4R)-(2,5-difluorobenzyl)-[1-(5-propylpyrimidin-2-yl)-4-tritylsulfanylpyrrolidin-2-ylmethyl]amine 在 三乙基硅烷 、 三氟乙酸 作用下， 以 乙腈 为溶剂， 生成 (3R,5S)-5-[[(2,5-difluorophenyl)methylamino]methyl]-1-(5-propylpyrimidin-2-yl)pyrrolidine-3-thiol
  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 cyanoborohydride 、 一水合肼 、 N,N-二异丙基乙胺 、 三苯基膦 、 三氟乙酸 、 zinc(II) chloride 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.91h， 生成 (2S,4R)-(2,5-difluorobenzyl)-[1-(5-propylpyrimidin-2-yl)-4-tritylsulfanylpyrrolidin-2-ylmethyl]amine
  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