2-azaspiro[4.4]non-7-ene-2,3-(S)-dicarboxylic acid di-tert-butyl ester | 394734-82-8

• 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: 2-azaspiro[4.4]non-7-ene-2,3-(S)-dicarboxylic acid di-tert-butyl ester
• 英文别名: di-tert-butyl (3S)-2-azaspiro[4.4]non-7-ene-2,3-dicarboxylate；(S)-DI-Tert-butyl2-azaspiro[4.4]non-7-ene-2,3-dicarboxylate；ditert-butyl (3S)-2-azaspiro[4.4]non-7-ene-2,3-dicarboxylate
• CAS: 394734-82-8
• 化学式: C₁₈H₂₉NO₄
• 分子量: 323.433
• InChiKey: FGZRZEJCTAAHER-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-azaspiro[4.4]non-7-ene-2,3-(S)-dicarboxylic acid di-tert-butyl ester 在 palladium on activated charcoal 盐酸 、 氢气 、 溶剂黄146 、 N,N-二异丙基乙胺 、 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 、 甲醇 、 二氯甲烷 为溶剂， -20.0 ℃ 、241.32 kPa 条件下， 反应 3.0h， 生成 (S)-2-((S)-2-Cyclohexyl-2-isobutoxycarbonylamino-acetyl)-2-aza-spiro[4.4]nonane-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Discovery of SCH446211 (SCH6):  A New Ketoamide Inhibitor of the HCV NS3 Serine Protease and HCV Subgenomic RNA Replication

  摘要：

  Introduction of various modified prolines at P-2 and optimization of the P-1 side chain led to the discovery of SCH6 (24, Table 2), a potent ketoamide inhibitor of the HCV NS3 serine protease. In addition to excellent enzyme potency (K-i* = 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA replication with IC50 and IC90 of 40 and 100 nM, respectively. Recently, antiviral activity of 24 was demonstrated with inhibition of the full-length genotype 2a HCV genome. In addition, 24 was found to restore the responsiveness of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA replicons.

  DOI：

  10.1021/jm060077j
• 作为产物：
  描述：

  (S)-N-叔丁氧羰基-2-吡咯烷酮-5-甲酸叔丁酯 在 Grubbs catalyst first generation 、 三乙基硼氢化锂 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 7.0h， 生成 2-azaspiro[4.4]non-7-ene-2,3-(S)-dicarboxylic acid di-tert-butyl ester
  参考文献：
  名称：

  [EN] MASP INHIBITORY COMPOUNDS AND USES THEREOF
  [FR] COMPOSÉS INHIBITEURS DE MASP ET LEURS UTILISATIONS

  摘要：

  本发明涉及新型甘霖结合凝集素（MBL）相关丝氨酸蛋白酶（MASP）抑制化合物，以及其类似物和衍生物，以及其制备方法，单独或组合用于治疗和/或预防疾病，以及用于生产药物治疗和/或预防疾病，特别是用于治疗和/或预防肾脏和心血管疾病以及缺血再灌注损伤。

  公开号：

  WO2020225095A1

文献信息

• NOVEL PEPTIDES AS NS3-SERINE PROTEASE INHIBITORS OF HEPATITIS C VIRUS
  申请人：Saksena Anil K.

  公开号：US20110117057A1

  公开（公告）日：2011-05-19

  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.

  本发明披露了具有HCV蛋白酶抑制活性的新化合物，以及制备这些化合物的方法。在另一种实施方式中，本发明披露了包含这些化合物的制药组合物，以及使用它们治疗与HCV蛋白酶相关的疾病的方法。
• MASP INHIBITORY COMPOUNDS AND USES THEREOF
  申请人：Bayer Aktiengesellschaft

  公开号：US20210246166A1

  公开（公告）日：2021-08-12

  The present invention relates to novel Mannose-binding lectin (MBL)-associated serine protease (MASP) inhibitory compounds, as well as analogues and derivatives thereof, to processes for the preparation thereof, to the use thereof alone or in combinations for treatment and/or prevention of diseases and to the use thereof for production of medicaments for treatment and/or prevention of diseases, especially for treatment and/or prevention of renal and cardiovascular disorders and of ischemia reperfusion injuries.
• USRE43298E1
  申请人：——

  公开号：USRE43298E1

  公开（公告）日：2012-04-03
• Discovery of SCH446211 (SCH6):  A New Ketoamide Inhibitor of the HCV NS3 Serine Protease and HCV Subgenomic RNA Replication
  作者：Stéphane L. Bogen、Ashok Arasappan、Frank Bennett、Kevin Chen、Edwin Jao、Yi-Tsung Liu、Raymond G. Lovey、Srikanth Venkatraman、Weidong Pan、Tajel Parekh、Russel E. Pike、Sumei Ruan、Rong Liu、Bahige Baroudy、Sony Agrawal、Robert Chase、Paul Ingravallo、John Pichardo、Andrew Prongay、Jean-Marc Brisson、Tony Y. Hsieh、Kuo-Chi Cheng、Scott J. Kemp、Odile E. Levy、Marguerita Lim-Wilby、Susan Y. Tamura、Anil K. Saksena、Viyyoor Girijavallabhan、F. George Njoroge

  DOI：10.1021/jm060077j

  日期：2006.5.1

  Introduction of various modified prolines at P-2 and optimization of the P-1 side chain led to the discovery of SCH6 (24, Table 2), a potent ketoamide inhibitor of the HCV NS3 serine protease. In addition to excellent enzyme potency (K-i* = 3.8 nM), 24 was also found to be a potent inhibitor of HCV subgenomic RNA replication with IC50 and IC90 of 40 and 100 nM, respectively. Recently, antiviral activity of 24 was demonstrated with inhibition of the full-length genotype 2a HCV genome. In addition, 24 was found to restore the responsiveness of the interferon regulatory factor 3 (IRF-3) in cells containing HCV RNA replicons.
• [EN] MASP INHIBITORY COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS INHIBITEURS DE MASP ET LEURS UTILISATIONS
  申请人：BAYER AG

  公开号：WO2020225095A1

  公开（公告）日：2020-11-12

  The present invention relates to novel Mannose-binding lectin (MBL)-associated serine protease (MASP) inhibitory compounds, as well as analogues and derivatives thereof, to processes for the preparation thereof, to the use thereof alone or in combinations for treatment and/or prevention of diseases and to the use thereof for production of medicaments for treatment and/or prevention of diseases, especially for treatment and/or prevention of renal and cardiovascular disorders and of ischemia reperfusion injuries.

  本发明涉及新型甘霖结合凝集素（MBL）相关丝氨酸蛋白酶（MASP）抑制化合物，以及其类似物和衍生物，以及其制备方法，单独或组合用于治疗和/或预防疾病，以及用于生产药物治疗和/或预防疾病，特别是用于治疗和/或预防肾脏和心血管疾病以及缺血再灌注损伤。