di-tert-butyl 2,2'-(((ethyne-1,2-diylbis(4,1-phenylene))bis(azanediyl))bis(carbonyl))(2S,2′S)-bis(pyrrolidine-1-carboxylate) | 1219630-39-3

• 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: di-tert-butyl 2,2'-(((ethyne-1,2-diylbis(4,1-phenylene))bis(azanediyl))bis(carbonyl))(2S,2′S)-bis(pyrrolidine-1-carboxylate)
• 英文别名: tert-butyl (2S)-2-[[4-[2-[4-[[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carbonyl]amino]phenyl]ethynyl]phenyl]carbamoyl]pyrrolidine-1-carboxylate
• CAS: 1219630-39-3
• 化学式: C₃₄H₄₂N₄O₆
• 分子量: 602.731
• InChiKey: HZKGIHTXCXJEDT-NSOVKSMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  44
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  di-tert-butyl 2,2'-(((ethyne-1,2-diylbis(4,1-phenylene))bis(azanediyl))bis(carbonyl))(2S,2′S)-bis(pyrrolidine-1-carboxylate) 在 盐酸 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.0h， 生成 (2S)-1-[(2R)-2-amino-3-phenylpropanoyl]-N-[4-[2-[4-[[(2S)-1-[(2R)-2-amino-3-phenylpropanoyl]pyrrolidine-2-carbonyl]amino]phenyl]ethynyl]phenyl]pyrrolidine-2-carboxamide
  参考文献：
  名称：

  HEPATITIS C VIRUS INHIBITORS

  摘要：

  公开号：

  EP2328865B1
• 作为产物：
  描述：

  对碘苯胺 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 di-tert-butyl 2,2'-(((ethyne-1,2-diylbis(4,1-phenylene))bis(azanediyl))bis(carbonyl))(2S,2′S)-bis(pyrrolidine-1-carboxylate)
  参考文献：
  名称：

  Redesigning of the cap conformation and symmetry of the diphenylethyne core to yield highly potent pan-genotypic NS5A inhibitors with high potency and high resistance barrier

  摘要：

  DOI：

  10.1016/j.ejmech.2021.114034

文献信息

• Hepatitis C Virus Inhibitors
  申请人：Belema Makonen

  公开号：US20100080772A1

  公开（公告）日：2010-04-01

  The present disclosure relates to compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in the treatment of HCV infection.

  本公开涉及化合物、组合物和治疗丙型肝炎病毒（HCV）感染的方法。还公开了含有这些化合物的药物组合物以及使用这些化合物治疗HCV感染的方法。
• HCV NS5A Replication Complex Inhibitors. Part 4.1 Optimization for Genotype 1a Replicon Inhibitory Activity
  作者：Denis R. St. Laurent、Michael H. Serrano-Wu、Makonen Belema、Min Ding、Hua Fang、Min Gao、Jason T. Goodrich、Rudolph G. Krause、Julie A. Lemm、Mengping Liu、Omar D. Lopez、Van N. Nguyen、Peter T. Nower、Donald R. O’Boyle、Bradley C. Pearce、Jeffrey L. Romine、Lourdes Valera、Jin-Hua Sun、Ying-Kai Wang、Fukang Yang、Xuejie Yang、Nicholas A. Meanwell、Lawrence B. Snyder

  DOI：10.1021/jm301796k

  日期：2014.3.13

  A series of symmetrical E-stilbene prolinamides that originated from the library-synthesized lead 3 was studied with respect to HCV genotype 1a (G-1a) and genotype 1b (G-1b) replicon inhibition and selectivity against BVDV and cytotoxicity. SAR emerging from an examination of the prolinamide cap region revealed 11 to be a selective HCV NS5A inhibitor exhibiting submicromolar potency against both G-1a and G-1b replicons. Additional structural refinements resulted in the identification of 30 as a potent, dual G-1a/1b HCV NS5A inhibitor.
• HCV NS5A replication complex inhibitors. Part 3: discovery of potent analogs with distinct core topologies
  作者：Omar D. Lopez、Van N. Nguyen、Denis R. St. Laurent、Makonen Belema、Michael H. Serrano-Wu、Jason T. Goodrich、Fukang Yang、Yuping Qiu、Amy S. Ripka、Peter T. Nower、Lourdes Valera、Mengping Liu、Donald R. O’Boyle、Jin-Hua Sun、Robert A. Fridell、Julie A. Lemm、Min Gao、Andrew C. Good、Nicholas A. Meanwell、Lawrence B. Snyder

  DOI：10.1016/j.bmcl.2012.11.086

  日期：2013.2

  In a recent disclosure,(1) we described the discovery of dimeric, prolinamide-based NS5A replication complex inhibitors exhibiting excellent potency towards an HCV genotype 1b replicon. That disclosure dealt with the SAR exploration of the peripheral region of our lead chemotype, and herein is described the SAR uncovered from a complementary effort that focused on the central core region. From this effort, the contribution of the core region to the overall topology of the pharmacophore, primarily vector orientation and planarity, was determined, with a set of analogs exhibiting < 10 nM EC50 in a genotype 1b replicon assay. (c) 2012 Elsevier Ltd. All rights reserved.
• HEPATITIS C VIRUS INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP2328865B1

  公开（公告）日：2017-05-31
• US8383094B2
  申请人：——

  公开号：US8383094B2

  公开（公告）日：2013-02-26