[(S)-1-(4,4-Dimethyl-2,6-dioxo-piperidin-1-ylmethyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester | 848777-31-1

• 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: [(S)-1-(4,4-Dimethyl-2,6-dioxo-piperidin-1-ylmethyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(2S)-1-(4,4-dimethyl-2,6-dioxopiperidin-1-yl)-3,3-dimethylbutan-2-yl]carbamate
• CAS: 848777-31-1
• 化学式: C₁₈H₃₂N₂O₄
• 分子量: 340.463
• InChiKey: ZDJZLWPUTVNFCY-GFCCVEGCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  75.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [(S)-1-(4,4-Dimethyl-2,6-dioxo-piperidin-1-ylmethyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester 在 盐酸 、 水 作用下， 以 1,4-二氧六环 为溶剂， 生成 1-[(2S)-2-amino-3,3-dimethylbutyl]-4,4-dimethylpiperidine-2,6-dione
  参考文献：
  名称：

  Second-Generation Highly Potent and Selective Inhibitors of the Hepatitis C Virus NS3 Serine Protease

  摘要：

  The hepatitis C virus (HCV) infection is a leading cause of chronic liver disease. The moderate efficacy along with side effects of the current pegylated interferon and ribavirin combination therapy underscores the need for more effective and safer new treatment. In an effort to improve upon our current clinical candidate, Boceprevir (SCH 503034), extensive SAR studies were performed on the P3 capping moieties. This led to the discovery of tert-leucinol derived cyclic imides as a potent series of novel P3 capping groups. Thus, the introduction of these imide caps improved the cell-based replicon EC90 by more than 10-fold. A number of imides with various substitutions, ring sizes, bicyclic systems, and heterocyclic rings were explored. The 4,4-dimethyl substituted glutarimide emerged as the best cap as exemplified in compound 21 (K-i* = 4 nM, EC90 = 40 nM). Systematic optimization of different positions (P', P3, and P1) of the inhibitor resulted in the identification of the lead compound 46, which had an excellent potency (K-i* = 4 nM, EC90 = 30 nM) and good pharmacokinetic profile (22% and 35% bioavailability in rats and dogs, respectively). X-ray structure of inhibitor 46 bound to the enzyme revealed that there was an additional hydrogen bonding interaction between one of the imide carbonyls and Cys159.

  DOI：

  10.1021/jm801238q
• 作为产物：
  描述：

  3,3-二甲基谷酰胺 、 (S)-()-N-Boc-叔亮氨醇 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 以51%的产率得到[(S)-1-(4,4-Dimethyl-2,6-dioxo-piperidin-1-ylmethyl)-2,2-dimethyl-propyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  3,4-(cyclopentyl)-fused proline compounds as inhibitors of hepatitis C virus NS3 serine protease

  摘要：

  本发明公开了具有HCV蛋白酶抑制活性的新化合物，以及制备这种化合物的方法。在另一实施方式中，本发明公开了包含这种化合物的药物组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。

  公开号：

  US20050197301A1

文献信息

• Novel synthesis of sterically hindered N-substituted lactams from imides
  作者：Mousumi Sannigrahi、Patrick Pinto、T.M. Chan、Neng-Yang Shih、F. George Njoroge

  DOI：10.1016/j.tetlet.2006.05.037

  日期：2006.7

  An efficient and practical synthesis of sterically hindered N-substituted lactams has been developed starting from simple starting materials. The stereochemistry of the synthetically useful N,N acetal intermediate has been established.

  从简单的起始原料开始，开发了一种有效和实用的位阻N-取代内酰胺的合成方法。已经建立了可合成使用的N，N乙缩醛中间体的立体化学。
• Macrocyclic Inhibitors of Hepatitis C Virus NS3 Serine Protease
  申请人：Venkatraman Srikanth

  公开号：US20110150835A1

  公开（公告）日：2011-06-23

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.
• US7342041B2
  申请人：——

  公开号：US7342041B2

  公开（公告）日：2008-03-11
• US7592419B2
  申请人：——

  公开号：US7592419B2

  公开（公告）日：2009-09-22
• [EN] HYDRAZIDO-PEPTIDES AS INHIBITORS OF HCV NS3-PROTEASE<br/>[FR] PEPTIDES HYDRAZIDO EN TANT QU'INHIBITEURS DE LA PROTÉASE NS3 DU HCV
  申请人：SCHERING CORP

  公开号：WO2008118332A2

  公开（公告）日：2008-10-02

  [EN] The present invention discloses novel compounds, which have HCV protease inhibitory activity as well as methods for preparing such compounds. In another embodiment, the invention discloses pharmaceutical compositions comprising such compounds as well as methods of using them to treat disorders associated with the HCV protease.
  [FR] La présente invention concerne de nouveaux composés ayant une activité inhibitrice de la protéase du HCV ainsi que des procédés pour les préparer. Dans un autre mode de réalisation, l'invention décrit des compositions pharmaceutiques comprenant ces composés ainsi que leurs procédés d'utilisation pour traiter les troubles associés à la protéase du HCV.