(4S,4''S)-4-<3'-(4''-benzyl-2''-oxo-oxazolidin-3''-yl)-3'-oxo-propyl>-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester | 223526-27-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (4S,4''S)-4-<3'-(4''-benzyl-2''-oxo-oxazolidin-3''-yl)-3'-oxo-propyl>-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (4S)-4-[3-[(4S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-3-oxopropyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 223526-27-0
• 化学式: C₂₃H₃₂N₂O₆
• 分子量: 432.517
• InChiKey: TWQDAGDEWUMLMV-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  85.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4S,4''S)-4-<3'-(4''-benzyl-2''-oxo-oxazolidin-3''-yl)-3'-oxo-propyl>-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester 在 甲醇 、 草酰氯 、 二甲基硫 、 sodium acetate 、 sodium hexamethyldisilazane 、 sodium cyanoborohydride 、 对甲苯磺酸 、 臭氧 、 二甲基亚砜 、 三乙胺 作用下， 反应 34.17h， 生成 tert-butyl N-[(2S)-1-[(3S)-1-[(2,4-dimethoxyphenyl)methyl]-2-oxopyrrolidin-3-yl]-3-oxopropan-2-yl]carbamate
  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 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 27.5h， 生成 (4S,4''S)-4-<3'-(4''-benzyl-2''-oxo-oxazolidin-3''-yl)-3'-oxo-propyl>-2,2-dimethyloxazolidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  （2S，4S）-和（2S，4R）-2-氨基-4-甲基癸酸的合成方法的改进：culicinins的立体化学分配。

  摘要：

  以谷氨酸衍生物为原料，以Evans的不对称烷基化为决定性步骤，完成了对（2 S，4 S）-和（2 S，4 R）-2-氨基-4-甲基癸酸的改进合成。测量了两种非对映异构体的NMR数据，并将其与天然产物的NMR数据进行比较。结果，这种新的氨基酸分子在culicinins中的立体化学被指定为（2 S，4 R）。版权所有©2011欧洲肽协会和John Wiley＆Sons，Ltd.。

  DOI：

  10.1002/psc.1376

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。
• US6995142B2
  申请人：——

  公开号：US6995142B2

  公开（公告）日：2006-02-07
• An improved synthesis of (2<i>S</i> , 4<i>S</i> )- and (2<i>S</i> , 4<i>R</i> )-2-amino-4-methyldecanoic acids: assignment of the stereochemistry of culicinins
  作者：Wei Zhang、Ning Ding、Yingxia Li

  DOI：10.1002/psc.1376

  日期：2011.8

  improved synthesis of (2S, 4S)‐ and (2S, 4R)‐2‐amino‐4‐methyldecanoic acids was accomplished using a glutamate derivative as starting material and Evans' asymmetric alkylation as the decisive step. The NMR data of the two diastereomers were measured and compared with those of the natural product. As a result, the stereochemistry of this novel amino acid unit in culicinins was assigned as (2S, 4R). Copyright

  以谷氨酸衍生物为原料，以Evans的不对称烷基化为决定性步骤，完成了对（2 S，4 S）-和（2 S，4 R）-2-氨基-4-甲基癸酸的改进合成。测量了两种非对映异构体的NMR数据，并将其与天然产物的NMR数据进行比较。结果，这种新的氨基酸分子在culicinins中的立体化学被指定为（2 S，4 R）。版权所有©2011欧洲肽协会和John Wiley＆Sons，Ltd.。
• Structure-Based Design, Synthesis, and Biological Evaluation of Irreversible Human Rhinovirus 3C Protease Inhibitors. 4. Incorporation of P₁ Lactam Moieties as <scp>l</scp>-Glutamine Replacements
  作者：Peter S. Dragovich、Thomas J. Prins、Ru Zhou、Stephen E. Webber、Joseph T. Marakovits、Shella A. Fuhrman、Amy K. Patick、David A. Matthews、Caroline A. Lee、Clifford E. Ford、Benjamin J. Burke、Paul A. Rejto、Thomas F. Hendrickson、Tove Tuntland、Edward L. Brown、James W. Meador、Rose Ann Ferre、James E. V. Harr、Maha B. Kosa、Stephen T. Worland

  DOI：10.1021/jm9805384

  日期：1999.4.1

  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.