(16aS,17aR,17bS)-13(S)-[[[[2,2-dimethyl-1(S)-[(2-oxo-1-piperidinyl)methyl]propyl]amino]carbonyl]amino]hexadecahydro-17,17-dimethyl-α,1,14-trioxo-N-2-propenyl-2H,12H-cyclopropa[3,4]pyrrolo[1,2-e][1,5,8]oxadiazacyclohexadecine-3(S)-acetamide | 848775-95-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (16aS,17aR,17bS)-13(S)-[[[[2,2-dimethyl-1(S)-[(2-oxo-1-piperidinyl)methyl]propyl]amino]carbonyl]amino]hexadecahydro-17,17-dimethyl-α,1,14-trioxo-N-2-propenyl-2H,12H-cyclopropa[3,4]pyrrolo[1,2-e][1,5,8]oxadiazacyclohexadecine-3(S)-acetamide
• 英文别名: 2-[(3S,13S,16S,17R,19S)-3-({[(2S)-3,3-dimethyl-1-(2-oxopiperidin-1-yl)butan-2-yl]carbamoyl}amino)-18,18-dimethyl-2,15-dioxo-5-oxa-1,14-diazatricyclo[14.4.0.0^{17,19}]icosan-13-yl]-2-oxo-N-(prop-2-en-1-yl)acetamide；2-[(3S,13S,16S,17R,19S)-3-[[(2S)-3,3-dimethyl-1-(2-oxopiperidin-1-yl)butan-2-yl]carbamoylamino]-18,18-dimethyl-2,15-dioxo-5-oxa-1,14-diazatricyclo[14.4.0.017,19]icosan-13-yl]-2-oxo-N-prop-2-enylacetamide
• CAS: 848775-95-1
• 化学式: C₃₆H₅₈N₆O₇
• 分子量: 686.893
• InChiKey: LPLJBNBRKUPAPU-VZYPYRSISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  49
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  166
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-[(2S)-2-isocyanato-3,3-dimethylbutyl]piperidin-2-one 、 N-allyl-2-((3S,13S,16aS,17aR,17bS)-13-amino-17,17-dimethyl-1,14-dioxohexadecahydro-2H,12H-cyclopropa[3,4]pyrrolo[1,2-e][1]oxa[5,8]diazacyclohexadecin-3-yl)-2-oxoacetamide hydrochloride 在 碳酸氢钠 作用下， 以 二氯甲烷 、 水 、 甲苯 为溶剂， 生成 (16aS,17aR,17bS)-13(S)-[[[[2,2-dimethyl-1(S)-[(2-oxo-1-piperidinyl)methyl]propyl]amino]carbonyl]amino]hexadecahydro-17,17-dimethyl-α,1,14-trioxo-N-2-propenyl-2H,12H-cyclopropa[3,4]pyrrolo[1,2-e][1,5,8]oxadiazacyclohexadecine-3(S)-acetamide
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Oxygen-Containing Macrocyclic Peptidomimetics as Inhibitors of HCV NS3 Protease

  摘要：

  HCV infection is considered a silent epidemic because most people infected do not develop acute symptoms. Instead, the disease progresses to a chronic state leading to cirrhosis and hepatocarcinoma. Novel therapies are needed to combat this major health threat. The HCV NS3 serine protease has been the target of continuous investigation because of its pivotal role in viral replication. Herein, we present the P1-P3 macrocyclization approach followed for identification of HCV NS3 inhibitors as potential back-up candidates to our first generation drug candidate, Sch 503034 (1). Different P1-P3 linkers were investigated to identify novel macrocyclic scaffolds. SAR exploration of P3-caps in the macrocyclic cores allowed the identification of L-serine derived macrocycle 32 (K-i* = 3 nM, EC90 = 30 nM) and allo-threonine derived macrocycle 36 (K-i* = 3 nM, EC90 = 30 nM) as potent HCV NS3 protease inhibitors.

  DOI：

  10.1021/jm801201u

文献信息

• [EN] MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE<br/>[FR] INHIBITEURS MACROCYCLIQUES DE LA SERINE PROTEASE NS3 DU VIRUS DE L'HEPATITE C
  申请人：SCHERING CORP

  公开号：WO2005030796A1

  公开（公告）日：2005-04-07

  The present invention discloses novel compounds which have HCV protease inhibitory activity as well as pharmaceutical compositions comprising such compounds and methods of using them to treat disorders associated with the HCV protease. The novel compounds typically include a 15-20 member macrocycle and have the general structure of structural Formula (1): wherein Z', L', M', R1, X and D are defined herein.

  本发明揭示了一种新型化合物，其具有HCV蛋白酶抑制活性，以及包含这些化合物的制药组合物和使用它们治疗与HCV蛋白酶相关的疾病的方法。这些新型化合物通常包括一个15-20成员的大环，并具有以下结构式（1）的一般结构，其中Z'、L'、M'、R1、X和D在此被定义。
• 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.
• US7592419B2
  申请人：——

  公开号：US7592419B2

  公开（公告）日：2009-09-22
• [EN] MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS NS3 SERINE PROTEASE<br/>[FR] INHIBITEURS MACROCYCLIQUES DE LA SÉRINE PROTÉASE NS3 DU VIRUS DE L'HÉPATITE C
  申请人：SCHERING CORP

  公开号：WO2009058856A1

  公开（公告）日：2009-05-07

  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.
• Design, Synthesis, and Evaluation of Oxygen-Containing Macrocyclic Peptidomimetics as Inhibitors of HCV NS3 Protease
  作者：Francisco Velázquez、Srikanth Venkatraman、Melissa Blackman、Patrick Pinto、Stéphane Bogen、Mousumi Sannigrahi、Kevin Chen、John Pichardo、Andrea Hart、Xiao Tong、Viyyoor Girijavallabhan、F. George Njoroge

  DOI：10.1021/jm801201u

  日期：2009.2.12

  HCV infection is considered a silent epidemic because most people infected do not develop acute symptoms. Instead, the disease progresses to a chronic state leading to cirrhosis and hepatocarcinoma. Novel therapies are needed to combat this major health threat. The HCV NS3 serine protease has been the target of continuous investigation because of its pivotal role in viral replication. Herein, we present the P1-P3 macrocyclization approach followed for identification of HCV NS3 inhibitors as potential back-up candidates to our first generation drug candidate, Sch 503034 (1). Different P1-P3 linkers were investigated to identify novel macrocyclic scaffolds. SAR exploration of P3-caps in the macrocyclic cores allowed the identification of L-serine derived macrocycle 32 (K-i* = 3 nM, EC90 = 30 nM) and allo-threonine derived macrocycle 36 (K-i* = 3 nM, EC90 = 30 nM) as potent HCV NS3 protease inhibitors.