(1S,3'S)-<2'-<1'-(2'',4''-dimethoxybenzyl)-2'-oxo-piperidin-3'-yl>-1-hydroxymethylethyl>-carbamic acid tert-butyl ester | 223526-46-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (1S,3'S)-<2'-<1'-(2'',4''-dimethoxybenzyl)-2'-oxo-piperidin-3'-yl>-1-hydroxymethylethyl>-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-1-[(3S)-1-[(2,4-dimethoxyphenyl)methyl]-2-oxopiperidin-3-yl]-3-hydroxypropan-2-yl]carbamate
• CAS: 223526-46-3
• 化学式: C₂₂H₃₄N₂O₆
• 分子量: 422.522
• InChiKey: PEFOKVGRQCQDFA-RDJZCZTQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1S,3'S)-<2'-<1'-(2'',4''-dimethoxybenzyl)-2'-oxo-piperidin-3'-yl>-1-hydroxymethylethyl>-carbamic acid tert-butyl ester 在 N-甲基吗啉 、 盐酸 、 草酰氯 、 sodium hexamethyldisilazane 、 二甲基亚砜 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.92h， 生成 (E)-(S)-5-[(S)-1-(2,4-Dimethoxy-benzyl)-2-oxo-piperidin-3-yl]-4-((S)-3-(4-fluoro-phenyl)-2-{(S)-3-methyl-2-[(5-methyl-isoxazole-3-carbonyl)-amino]-butyrylamino}-propionylamino)-pent-2-enoic acid ethyl ester
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 4. Incorporation of P₁ Lactam Moieties as l-Glutamine Replacements

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of various human rhinovirus (HRV) 3C protease (3CP) inhibitors which incorporate P-1 lactam moieties in lieu of an L-glutamine residue are described. These compounds are comprised of a tripeptidyl or peptidomimetic binding determinant and an ethyl propenoate Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. The P-1-lactam-containing inhibitors display significantly increased 3CP inhibition activity along with improved antirhinoviral properties relative to corresponding L-glutamine-derived molecules. In addition, several lactam-containing compounds exhibit excellent selectivity for HRV 3CP over several other serine and cysteine proteases and are not appreciably degraded by a variety of biological agents. One of the most potent inhibitors (AG7088, mean antirhinoviral EC90 0.10 approximate to mu M, n = 46 serotypes) is shown to warrant additional preclinical development to explore its potential for use as an antirhinoviral agent.

  DOI：

  10.1021/jm9805384
• 作为产物：
  描述：

  (4S)-4-(2'-carboxyethyl)-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester 在 sodium perborate 、 硼烷四氢呋喃络合物 、 pyridine-SO3 complex 、 sodium acetate 、 sodium hexamethyldisilazane 、 三甲基乙酰氯 、 sodium cyanoborohydride 、 对甲苯磺酸 、 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二甲基亚砜 为溶剂， 反应 58.83h， 生成 (1S,3'S)-<2'-<1'-(2'',4''-dimethoxybenzyl)-2'-oxo-piperidin-3'-yl>-1-hydroxymethylethyl>-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 4. Incorporation of P₁ Lactam Moieties as l-Glutamine Replacements

  摘要：

  The structure-based design, chemical synthesis, and biological evaluation of various human rhinovirus (HRV) 3C protease (3CP) inhibitors which incorporate P-1 lactam moieties in lieu of an L-glutamine residue are described. These compounds are comprised of a tripeptidyl or peptidomimetic binding determinant and an ethyl propenoate Michael acceptor moiety which forms an irreversible covalent adduct with the active site cysteine residue of the 3C enzyme. The P-1-lactam-containing inhibitors display significantly increased 3CP inhibition activity along with improved antirhinoviral properties relative to corresponding L-glutamine-derived molecules. In addition, several lactam-containing compounds exhibit excellent selectivity for HRV 3CP over several other serine and cysteine proteases and are not appreciably degraded by a variety of biological agents. One of the most potent inhibitors (AG7088, mean antirhinoviral EC90 0.10 approximate to mu M, n = 46 serotypes) is shown to warrant additional preclinical development to explore its potential for use as an antirhinoviral agent.

  DOI：

  10.1021/jm9805384

文献信息

• Antipicornaviral compounds and compositons, their pharmaceutical uses, and materials for their synthesis
  申请人：——

  公开号：US20030130204A1

  公开（公告）日：2003-07-10

  Peptido and peptidomimetic compounds of the formula: 1 wherein the formula variables are as defined in the disclosure, 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 RVP. Intermediates and synthetic methods for preparing such compounds are also provided.

  肽和肽类似化合物的公式为：1，其中公式变量如披露中所定义，有利地抑制或阻止了小肠病毒3C蛋白酶的生物活性。这些化合物以及含有这些化合物的制药组合物，对于治疗感染一种或多种小肠病毒（如RVP）的患者或宿主是有用的。还提供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：Dragovich Scott Peter

  公开号：US20060046966A1

  公开（公告）日：2006-03-02

  Peptido and peptidomimetic compounds of the formula: wherein the formula variables are as defined in the disclosure, 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 RVP. Intermediates and synthetic methods for preparing such compounds are also provided.

  肽和类肽模拟化合物的公式如下：其中公式变量如披露中所定义，有利地抑制或阻断小肠病毒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RVP）的患者或宿主非常有用。还提供了制备这些化合物的中间体和合成方法。
• Antipicornaviral compounds, their preparation and use
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP1329457A2

  公开（公告）日：2003-07-23

  Peptido and peptidomimetic compounds of formula (I) wherein the formula variables are as defined in the disclosure, 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 RVP. Intermediates and synthetic methods for preparing such compounds are also provided.

  式(I)的拟肽和拟肽化合物（其中式中的变量如本公开所定义）可有效抑制或阻断皮卡病毒 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可用于治疗感染一种或多种皮卡病毒（如 RVP）的患者或宿主。还提供了制备此类化合物的中间体和合成方法。
• ANTIPICORNAVIRAL COMPOUNDS, THEIR PREPARATION AND USE
  申请人：AGOURON PHARMACEUTICALS, INC.

  公开号：EP1073672B1

  公开（公告）日：2003-08-27
• US6531452B1
  申请人：——

  公开号：US6531452B1

  公开（公告）日：2003-03-11