(2R)-3-(4-Fluorophenyl)-2-trifluoromethane-sulfonyloxypropionic Acid Methyl Ester | 328273-04-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磺酸及其衍生物
• 英文名称: (2R)-3-(4-Fluorophenyl)-2-trifluoromethane-sulfonyloxypropionic Acid Methyl Ester
• 英文别名: Methyl (2R)-3-(4-fluorophenyl)-2-(trifluoromethylsulfonyloxy)propanoate
• CAS: 328273-04-7
• 化学式: C₁₁H₁₀F₄O₅S
• 分子量: 330.257
• InChiKey: JYMSXWULQDPNDG-SECBINFHSA-N

物化性质

• 沸点：
  352.9±42.0 °C(Predicted)
• 密度：
  1.476±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  78
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2R)-3-(4-Fluorophenyl)-2-trifluoromethane-sulfonyloxypropionic Acid Methyl Ester 在 palladium on activated charcoal 、 四(三苯基膦)钯 吗啉 、 N-甲基吗啉 、 盐酸 、 lithium hydroxide 、 氢气 、 sodium hydride 、 1-羟基苯并三唑 、 caesium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 73.5h， 生成 ethyl (E,4S)-4-[[(2R,5S)-2-[(4-fluorophenyl)methyl]-6-methyl-5-[(5-methylisoxazole-3-carbonyl)amino]-4-oxo-heptanoyl]amino]-5-phenyl-pent-2-enoate
  参考文献：
  名称：

  Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters

  摘要：

  The proteolytic processing of polyproteins by the 3CL protease of severe acute respiratory syndrome coronavirus is essential for the viral propagation. A series of tripeptide alpha,beta-unsaturated esters and ketomethylene isosteres, including AG7088, are synthesized and assayed to target the 3CL protease. Though AG7088 is inactive (IC50 > 100 mu M), the ketomethylene isosteres and tripeptide alpha,beta-unsaturated esters containing both P1 and P2 phenylalanine residues show modest inhibitory activity (IC50 = 11-39 mu M). The Phe-Phe dipeptide inhibitors 18a-e are designed on the basis of computer modeling of the enzyme-inhibitor complex. The most potent inhibitor 18c with an inhibition constant of 0.52 mu M is obtained by condensation of the Phe-Phe dipeptide alpha,beta-unsaturated ester with 4-(dimethylamino)cinnamic acid. The cell-based assays also indicate that 18c is a nontoxic anti-SARS agent with an EC50 value of 0.18 mu M. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.05.065
• 作为产物：
  描述：

  (r)-3-(4-氟苯基)-2-羟基丙酸甲酯 、 2,6-二甲基吡啶 在 盐酸 、 trifluoromethanesulfonic acid anhydride 作用下， 以 二氯甲烷 为溶剂， 生成 (2R)-3-(4-Fluorophenyl)-2-trifluoromethane-sulfonyloxypropionic Acid Methyl Ester
  参考文献：
  名称：

  Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis

  摘要：

  披露了具有以下公式的化合物： 1 其中公式变量如本文所述定义，这些化合物能够有优势地抑制或阻断小RNA病毒3C蛋白酶的生物学活性。还披露了具有以下公式的化合物： 2 其中公式变量如本文所述定义，这些化合物能够有优势地抑制或阻断小RNA病毒3C蛋白酶的生物学活性。这些化合物以及含有这些化合物的药物组合物对于治疗感染了一种或多种小RNA病毒的患者或宿主是有用的，例如鼻病毒3C蛋白酶。还描述了用于制备这些化合物的中间体和合成方法。

  公开号：

  US20010047006A1

文献信息

• [EN] ANTIPICORNAVIRAL COMPOUNDS AND COMPOSITIONS, THEIR PHARMACEUTICAL USES, AND MATERIALS FOR THEIR SYNTHESIS<br/>[FR] COMPOSES ET COMPOSITIONS ANTI-PICORNAVIRUS; UTILISATIONS PHARMACEUTIQUES ET MATERIAUX EMPLOYES POUR LEUR SYNTHESE
  申请人：AGOURON PHARMA

  公开号：WO2001040189A1

  公开（公告）日：2001-06-07

  Compounds of formula (I), where the formula variables are as defined herein, are disclosed that advantageously inhibit or block the biological activity of the picornaviral 3C protease. Also disclosed are compounds of formula (II) where the formula variables are as defined herein that advantageously inhibit or block the biological activity of the picornaviral 3C protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with one or more picornaviruses, such as rhinovirus 3C proteases. Intermediates and synthetic methods for preparing such compounds are also described.

  本发明披露了式(I)的化合物，其中式变量如本文所定义，这些化合物有利地抑制或阻断了小肠病毒3C蛋白酶的生物活性。本发明还披露了式(II)的化合物，其中式变量如本文所定义，这些化合物有利地抑制或阻断了小肠病毒3C蛋白酶的生物活性。这些化合物以及含有这些化合物的药物组合物，对于治疗感染一种或多种小肠病毒（如鼻病毒3C蛋白酶）的患者或宿主非常有用。还描述了制备这些化合物的中间体和合成方法。
• ANTIPICORNAVIRAL COMPOUNDS AND COMPOSITIONS, THEIR PHARMACEUTICAL USES, AND MATERIALS FOR THEIR SYNTHESIS
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP1252145A1

  公开（公告）日：2002-10-30
• US6514997B2
  申请人：——

  公开号：US6514997B2

  公开（公告）日：2003-02-04
• Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters
  作者：Jiun-Jie Shie、Jim-Min Fang、Tun-Hsun Kuo、Chih-Jung Kuo、Po-Huang Liang、Hung-Jyun Huang、Yin-Ta Wu、Jia-Tsrong Jan、Yih-Shyun E. Cheng、Chi-Huey Wong

  DOI：10.1016/j.bmc.2005.05.065

  日期：2005.9

  The proteolytic processing of polyproteins by the 3CL protease of severe acute respiratory syndrome coronavirus is essential for the viral propagation. A series of tripeptide alpha,beta-unsaturated esters and ketomethylene isosteres, including AG7088, are synthesized and assayed to target the 3CL protease. Though AG7088 is inactive (IC50 > 100 mu M), the ketomethylene isosteres and tripeptide alpha,beta-unsaturated esters containing both P1 and P2 phenylalanine residues show modest inhibitory activity (IC50 = 11-39 mu M). The Phe-Phe dipeptide inhibitors 18a-e are designed on the basis of computer modeling of the enzyme-inhibitor complex. The most potent inhibitor 18c with an inhibition constant of 0.52 mu M is obtained by condensation of the Phe-Phe dipeptide alpha,beta-unsaturated ester with 4-(dimethylamino)cinnamic acid. The cell-based assays also indicate that 18c is a nontoxic anti-SARS agent with an EC50 value of 0.18 mu M. (c) 2005 Elsevier Ltd. All rights reserved.
• Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis
  申请人：——

  公开号：US20010047006A1

  公开（公告）日：2001-11-29

  Compounds of the formula: 1 where the formula variables are as defined herein, are disclosed that advantageously inhibit or block the biological activity of the picornaviral 3C protease. Also disclosed are compounds of the formula: 2 where the formula variables are as defined herein that advantageously inhibit or block the biological activity of the picornaviral 3C protease. These compounds, as well as pharmaceutical compositions containing these compounds, are useful for treating patients or hosts infected with one or more picornaviruses, such as rhinovirus 3C proteases. Intermediates and synthetic methods for preparing such compounds are also described.

  披露了具有以下公式的化合物： 1 其中公式变量如本文所述定义，这些化合物能够有优势地抑制或阻断小RNA病毒3C蛋白酶的生物学活性。还披露了具有以下公式的化合物： 2 其中公式变量如本文所述定义，这些化合物能够有优势地抑制或阻断小RNA病毒3C蛋白酶的生物学活性。这些化合物以及含有这些化合物的药物组合物对于治疗感染了一种或多种小RNA病毒的患者或宿主是有用的，例如鼻病毒3C蛋白酶。还描述了用于制备这些化合物的中间体和合成方法。