tert-butyl N6-(tert-butoxycarbonyl)-N2-(((8S,11R)-8-isopropyl-3,10-dioxo-6-oxa-2,9-diaza-1(1,4)-benzenacyclododecaphane-11-yl)carbamoyl)-L-lysinate | 1198186-49-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: tert-butyl N6-(tert-butoxycarbonyl)-N2-(((8S,11R)-8-isopropyl-3,10-dioxo-6-oxa-2,9-diaza-1(1,4)-benzenacyclododecaphane-11-yl)carbamoyl)-L-lysinate
• 英文别名: tert-butyl (S)-6-tert-butoxycarbonylamino-2-[3-((8S,11R)-8-isopropyl-3,10-dioxo-6-oxa-2,9-diazabicyclo[11.2.2]heptadeca-1(16),13(17),14-trien-11-yl)ureido]hexanoate；tert-butyl(S)-6-tert-butoxycarbonylamino-2-[3-((8S,11R)-8-isopropyl-3,10-dioxo-6-oxa-2,9-diazabicyclo[11.2.2]heptadeca-1(16),13(17),14-trien-11-yl)ureido]hexanoate；tert-butyl (2S)-2-[[(8S,11R)-3,10-dioxo-8-propan-2-yl-6-oxa-2,9-diazabicyclo[11.2.2]heptadeca-1(15),13,16-trien-11-yl]carbamoylamino]-6-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate
• CAS: 1198186-49-0
• 化学式: C₃₃H₅₃N₅O₈
• 分子量: 647.813
• InChiKey: BEMIOWCTABNUFL-JIMJEQGWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  173
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl N6-(tert-butoxycarbonyl)-N2-(((8S,11R)-8-isopropyl-3,10-dioxo-6-oxa-2,9-diaza-1(1,4)-benzenacyclododecaphane-11-yl)carbamoyl)-L-lysinate 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 水 为溶剂， 反应 2.0h， 生成 (S)-6-Amino-2-[3-((8S,11R)-8-isopropyl-3,10-dioxo-6-oxa-2,9-diazabicyclo[11.2.2]heptadeca-1(16),13(17),14-trien-11-yl)ureido]hexanoic acid
  参考文献：
  名称：

  MACROCYCLIC UREA AND SULFAMIDE DERIVATIVES AS INHIBITORS OF TAFIa

  摘要：

  该发明涉及式(I)的化合物，这些化合物是激活的凝血酶可激活的纤溶抑制剂的抑制剂。式I的化合物适用于生产用于预防、次级预防和治疗与血栓形成、栓塞、高凝血性或纤维化变化相关的一个或多个疾病的药物。

  公开号：

  US20110178130A1
• 作为产物：
  描述：

  N-Boc-L-缬氨醇 在 N-羟基-7-氮杂苯并三氮唑 、 三异丙基硅烷 、 水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 tert-butyl N6-(tert-butoxycarbonyl)-N2-(((8S,11R)-8-isopropyl-3,10-dioxo-6-oxa-2,9-diaza-1(1,4)-benzenacyclododecaphane-11-yl)carbamoyl)-L-lysinate
  参考文献：
  名称：

  MACROCYCLIC UREA AND SULFAMIDE DERIVATIVES AS INHIBITORS OF TAFIa

  摘要：

  该发明涉及式(I)的化合物，这些化合物是激活的凝血酶可激活的纤溶抑制剂的抑制剂。式I的化合物适用于生产用于预防、次级预防和治疗与血栓形成、栓塞、高凝血性或纤维化变化相关的一个或多个疾病的药物。

  公开号：

  US20110178130A1

文献信息

• MACROCYCLIC UREA AND SULFAMIDE DERIVATIVES AS INHIBITORS OF TAFIA
  申请人：Kallus Christopher

  公开号：US20140039011A1

  公开（公告）日：2014-02-06

  The invention relates to compounds of the formula (I) which are inhibitors of activated thrombin-activable fibrinolysis inhibitor. The compounds of the formula I are suitable for producing medicaments for prophylaxis, secondary prevention and treatment of one or more disorders associated with thromboses, embolisms, hypercoagulability or fibrotic changes.

  本发明涉及公式（I）的化合物，它们是活化的凝血酶-可激活纤溶抑制剂的抑制剂。公式I的化合物适用于生产预防、次级预防和治疗与血栓、栓塞、高凝状态或纤维化变化相关的一个或多个疾病的药物。
• Macrocyclic urea and sulfamide derivatives as inhibitors of TAFIa
  申请人：Kallus Christopher

  公开号：US08580777B2

  公开（公告）日：2013-11-12

  The invention relates to compounds of the formula (I) which are inhibitors of activated thrombin-activable fibrinolysis inhibitor. The compounds of the formula I are suitable for producing medicaments for prophylaxis, secondary prevention and treatment of one or more disorders associated with thromboses, embolisms, hypercoagulability or fibrotic changes.

  本发明涉及式(I)的化合物，它们是激活的凝血酶激活纤溶抑制剂的抑制剂。式(I)的化合物适用于制备用于预防、次级预防和治疗与血栓、栓塞、高凝状态或纤维化变化有关的一个或多个疾病的药物。
• Macrocyclic urea and sulfamide derivatives as inhibitors of tafia
  申请人：Kallus Christopher

  公开号：US08722655B2

  公开（公告）日：2014-05-13

  The invention relates to compounds of the formula (I) which are inhibitors of activated thrombin-activable fibrinolysis inhibitor. The compounds of the formula I are suitable for producing medicaments for prophylaxis, secondary prevention and treatment of one or more disorders associated with thromboses, embolisms, hypercoagulability or fibrotic changes.

  本发明涉及式(I)的化合物，它们是激活的凝血酶激活纤溶抑制剂的抑制剂。式(I)的化合物适用于制备用于预防、次级预防和治疗与血栓、栓塞、高凝状态或纤维化变化有关的一种或多种疾病的药物。
• Automated Design of Macrocycles for Therapeutic Applications: From Small Molecules to Peptides and Proteins
  作者：Dan Sindhikara、Michael Wagner、Paraskevi Gkeka、Stefan Güssregen、Garima Tiwari、Gerhard Hessler、Engin Yapici、Ziyu Li、Andreas Evers

  DOI：10.1021/acs.jmedchem.0c01500

  日期：2020.10.22

  Macrocycles and cyclic peptides are increasingly attractive therapeutic modalities as they often have improved affinity, are able to bind to extended protein surfaces, and otherwise have favorable properties. Macrocyclization of a known binder may stabilize its bioactive conformation and improve its metabolic stability, cell permeability, and in certain cases oral bioavailability. Herein, we present implementation and application of an approach that automatically generates, evaluates, and proposes cyclizations utilizing a library of well-established chemical reactions and reagents. Using the three-dimensional (3D) conformation of the linear molecule in complex with a target protein as the starting point, this approach identifies attachment points, generates linkers, evaluates their geometric compatibility, and ranks the resulting molecules with respect to their predicted conformational stability and interactions with the target protein. As we show here with prospective and retrospective case studies, this procedure can be applied for the macrocyclization of small molecules and peptides and even PROteolysis TArgeting Chimeras (PROTACs) and proteins.
• MAKROCYCLISCHE HARNSTOFF- UND SULFAMIDDERIVATE ALS INHIBITOREN VON TAFIA
  申请人：Sanofi-Aventis

  公开号：EP2300462A1

  公开（公告）日：2011-03-30