(S)-tert-butyl 4-(3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylate | 249736-39-8

• 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: (S)-tert-butyl 4-(3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylate
• 英文别名: tert-butyl (S)-2,2-dimethyl-4-(3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-3-oxopropyl)oxazolidine-3-carboxylate；tert-butyl (4S)-4-[3-[(4R)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]-3-oxopropyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate
• CAS: 249736-39-8
• 化学式: C₂₃H₃₂N₂O₆
• 分子量: 432.517
• InChiKey: TWQDAGDEWUMLMV-ZWKOTPCHSA-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：

  (S)-tert-butyl 4-(3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylate 在 N-甲基吗啉 、 盐酸 、 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 、 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 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 56.75h， 生成 (E)-(S)-4-[(S)-2-((S)-2-Benzyloxycarbonylamino-4-methyl-pentanoylamino)-3-phenyl-propionylamino]-5-[(R)-1-(2,4-dimethoxy-benzyl)-2-oxo-pyrrolidin-3-yl]-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 三乙胺 、 lithium chloride 作用下， 以 四氢呋喃 为溶剂， 反应 27.5h， 生成 (S)-tert-butyl 4-(3-((R)-4-benzyl-2-oxooxazolidin-3-yl)-3-oxopropyl)-2,2-dimethyloxazolidine-3-carboxylate
  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

• RENIN INHIBITORS
  申请人：Baldwin John J.

  公开号：US20100184805A1

  公开（公告）日：2010-07-22

  Disclosed are aspartic protease inhibitors represented by the following structural formula: and pharmaceutically acceptable salts thereof. These compounds are orally active and bind to aspartic proteases to inhibit their activity. They are useful in the treatment or amelioration of diseases associated with aspartic protease activity. The present invention is also directed to pharmaceutical compositions comprising a compound described herein or enantiomers, diastereomers, or salts thereof and a pharmaceutically acceptable carrier or excipient.

  揭示了以下结构式所代表的天冬氨酸蛋白酶抑制剂，以及其药学上可接受的盐。这些化合物可经口给药，并结合到天冬氨酸蛋白酶上以抑制其活性。它们在治疗或改善与天冬氨酸蛋白酶活性有关的疾病方面具有用途。本发明还涉及包括本文所述化合物或其对映体、二对映体或盐以及药学上可接受的载体或赋形剂的制药组合物。
• Stereoselective synthesis of fully protected (2S,4S,6S)-2-amino-6-hydroxy-4-methyl-8-oxodecanoic acid (AHMOD)
  作者：Wei Zhang、Xiangpeng Li、Ning Ding、Yingxia Li

  DOI：10.1002/psc.1433

  日期：2012.3

  The stereocontrolled synthesis of fully protected (2S,4S,6S)‐2‐amino‐6‐hydroxy‐4‐methyl‐8‐oxodecanoic acid was accomplished using a glutamate derivative as starting material. The key steps of this stereochemical synthetic pathway involved an Evans asymmetric alkylation, a Sharpless asymmetric epoxidation, and a Grignard reaction. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd

  完全受保护的（2 S，4 S，6 S）-2-氨基-6-羟基-4-甲基-8-氧代十二烷酸的立体控制合成是以谷氨酸衍生物为原料完成的。该立体化学合成途径的关键步骤涉及埃文斯不对称烷基化，夏普斯不对称不对称环氧化和格氏反应。版权所有©2012欧洲肽协会和John Wiley＆Sons，Ltd.
• Piperidine derivatives as renin inhibitors
  申请人：Baldwin John J.

  公开号：US20090318501A1

  公开（公告）日：2009-12-24

  The present invention is directed to aspartic protease inhibitors represented by the following structural formula; or a pharmaceutically acceptable salt thereof. The present invention is also directed to pharmaceutical compositions comprising the aspartic protease inhibitors of Structural Formula (I). Methods of antagonizing one or more aspartic proteases in a subject in need thereof, and methods for treating an aspartic protease mediated disorder in a subject using these aspartic protease inhibitors are also disclosed.

  本发明涉及以下结构式所表示的天冬氨酸蛋白酶抑制剂; 或其药学上可接受的盐。本发明还涉及包括结构式（I）的天冬氨酸蛋白酶抑制剂的制药组合物。本发明还揭示了在需要拮抗一种或多种天冬氨酸蛋白酶的主体中拮抗一种或多种天冬氨酸蛋白酶的方法，以及使用这些天冬氨酸蛋白酶抑制剂治疗天冬氨酸蛋白酶介导的疾病的方法。
• Aspartic Protease Inhibitors
  申请人：Baldwin John J.

  公开号：US20100048636A1

  公开（公告）日：2010-02-25

  The present invention is directed to aspartic protease inhibitors. Certain aspartic protease inhibitors of the invention can be represented by the following structural formula or a pharmaceutically acceptable salt thereof. The present invention is also directed to pharmaceutical compositions comprising the disclosed aspartic protease inhibitors. The present invention is further directed to methods of antagonizing one or more aspartic proteases in a subject in need thereof, and methods for treating an aspartic protease mediated disorder in a subject using the disclosed aspartic protease inhibitors.

  本发明涉及天冬氨酸蛋白酶抑制剂。本发明所述的某些天冬氨酸蛋白酶抑制剂可以用以下结构式或其药学上可接受的盐来表示。本发明还涉及包括所述天冬氨酸蛋白酶抑制剂的药物组合物。本发明还涉及在需要拮抗一种或多种天冬氨酸蛋白酶的主体中的方法，以及使用所述天冬氨酸蛋白酶抑制剂治疗天冬氨酸蛋白酶介导的疾病的方法。
• Renin Inhibitors
  申请人：Baldwin John J.

  公开号：US20090312369A1

  公开（公告）日：2009-12-17

  The present invention is directed to aspartic protease inhibitors represented by the following structural formula (I), or a pharmaceutically acceptable salt thereof. The present invention is also directed to pharmaceutical compositions comprising the aspartic protease inhibitors of Structural Formula (I). Methods of antagonizing one or more aspartic proteases in a subject in need thereof, and methods for treating an aspartic protease mediated disorder in a subject using these aspartic protease inhibitors are also disclosed.

  本发明涉及以下结构式(I)所表示的天冬氨酸蛋白酶抑制剂，或其药学上可接受的盐。本发明还涉及包括结构式(I)的天冬氨酸蛋白酶抑制剂的制药组合物。本发明还公开了用这些天冬氨酸蛋白酶抑制剂拮抗一个或多个需要治疗的天冬氨酸蛋白酶的方法，以及用这些天冬氨酸蛋白酶抑制剂治疗一个天冬氨酸蛋白酶介导的疾病的方法。