(2S,4R)-2-Hydroxymethyl-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl ester | 337307-10-5

• 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-Hydroxymethyl-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl ester
• 英文别名: (2S,4R)-2-hydroxymethyl-4-tritylsulfanylpyrrolidine-1-carboxylic acid tert-butyl ester；tert-butyl (2S,4R)-2-(hydroxymethyl)-4-tritylsulfanylpyrrolidine-1-carboxylate
• CAS: 337307-10-5
• 化学式: C₂₉H₃₃NO₃S
• 分子量: 475.652
• InChiKey: DVSPQOWIGAOONB-IZZNHLLZSA-N

物化性质

• 沸点：
  590.2±50.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  75.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S,4R)-2-Hydroxymethyl-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl ester 在 sodium hydride 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 (2S,4R)-2-(2,4,5-Trifluoro-benzyloxymethyl)-4-tritylsulfanyl-pyrrolidine
  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-顺式-4-羟基-L-脯氨酸甲酯 在 锂硼氢 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 7.33h， 生成 (2S,4R)-2-Hydroxymethyl-4-tritylsulfanyl-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Pyrrolidine inhibitors of human cytosolic phospholipase A2. Part 2

  摘要：

  We synthesized a potent and crystallized human cytosolic phospholipase A(2)alpha inhibitor, pyrrophenone (6) which inhibits the isolated enzyme with an IC50 value of 4.2 nM. Pyrrophenone shows potent inhibition of arachidonic acid release, prostaglandin E-2, thromboxane B-2, and leukotriene B-4 formation in human whole blood. The magnitudes of prostaglandin E-2 and thromboxane B-2 inhibition are the same as those of indomethacin. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00003-8

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。
• [EN] PYRROLIDINE DERIVATIVES AS METALLOPROTEASE INHIBITORS<br/>[FR] DERIVES DE PYRROLIDINE UTILISES EN TANT QU'INHIBITEURS DE METALLOPROTEASE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2002008185A1

  公开（公告）日：2002-01-31

  The present invention relates to compounds of formula (I) wherein R?1, R2, R3, R4, R5, R6¿, Y, n, m, o. p and q are as defined in the description and the claims and dimeric forms and/or pharmaceutically acceptable esters, and/or salts thereof. The compounds are useful as inhibitors of metalloproteases, e.g. zinc proteases, particularly zinc hydrolases, and which are effective in treating disease states are associated with vasoconstriction of increasing occurrences.

  本发明涉及公式（I）的化合物，其中R？1，R2，R3，R4，R5，R6¿，Y，n，m，o。 p和q如描述和要求中所定义的二聚体形式和/或药学上可接受的酯和/或盐。这些化合物可用作金属蛋白酶抑制剂，例如锌蛋白酶，特别是锌水解酶，并且有效治疗与血管收缩增加有关的疾病状态。
• PYRROLIDINE DERIVATIVES AS METALLOPROTEASE INHIBITORS
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1303486A1

  公开（公告）日：2003-04-23
• PYRIMIDINE DERIVATIVES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1303507A1

  公开（公告）日：2003-04-23
• US6660738B2
  申请人：——

  公开号：US6660738B2

  公开（公告）日：2003-12-09