2-<(phenylmethoxy)carbonyl>-6,10-dithia-2-azaspiro<4,5>-decane-3(S)-carboxylic acid methyl ester | 113490-83-8

• 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-<(phenylmethoxy)carbonyl>-6,10-dithia-2-azaspiro<4,5>-decane-3(S)-carboxylic acid methyl ester
• 英文别名: 2-O-benzyl 3-O-methyl (3S)-6,10-dithia-2-azaspiro[4.5]decane-2,3-dicarboxylate
• CAS: 113490-83-8
• 化学式: C₁₇H₂₁NO₄S₂
• 分子量: 367.49
• InChiKey: RGEKEKDVDQJZMN-AWEZNQCLSA-N

物化性质

• 沸点：
  519.8±50.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  106
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-<(phenylmethoxy)carbonyl>-6,10-dithia-2-azaspiro<4,5>-decane-3(S)-carboxylic acid methyl ester 在 氢溴酸 、 溶剂黄146 作用下， 反应 2.0h， 生成 6,10-dithia-2-azaspiro<4.5>-decane-3(S)-carboxylic acid methyl ester hydrobromide
  参考文献：
  名称：

  Synthesis and pharmacological activity of angiotensin-converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines

  摘要：

  The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described. These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition. The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril. The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.

  DOI：

  10.1021/jm00399a033
• 作为产物：
  描述：

  N-cbz-4-氧-L-脯氨酸 在 氯化亚砜 、 对甲苯磺酸 作用下， 以 溶剂黄146 为溶剂， 反应 22.0h， 生成 2-<(phenylmethoxy)carbonyl>-6,10-dithia-2-azaspiro<4,5>-decane-3(S)-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis and pharmacological activity of angiotensin-converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines

  摘要：

  The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described. These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition. The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril. The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.

  DOI：

  10.1021/jm00399a033

文献信息

• Novel peptides as NS3-serine protease inhibitors of hepatitis C virus
  申请人：Saksena K. Anil

  公开号：US20070032433A1

  公开（公告）日：2007-02-08

  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.

  本发明揭示了具有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，本发明揭示了包含这些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。
• INHIBITORS OF SERINE PROTEASES, PARTICULARLY HCV NS3-NS4A PROTEASE
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：US20140031277A1

  公开（公告）日：2014-01-30

  The present invention relates to compounds of formula I: or a pharmaceutically acceptable salt or mixtures thereof that inhibit serine protease activity, particularly the activity of hepatitis C virus NS 3 -NS 4 A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The invention further relates to compositions comprising these compounds either for ex vivo use or for administration to a patient suffering from HCV infection and to processes for preparing the compounds. The invention also relates to methods of treating an HCV infection in a patient by administering a composition comprising a compound of this invention. The invention further relates to processes for preparing these compounds.

  本发明涉及以下式I的化合物：或其药学上可接受的盐或混合物，其抑制丝氨酸蛋白酶活性，特别是丙型肝炎病毒NS3-NS4A蛋白酶的活性。因此，它们通过干扰丙型肝炎病毒的生命周期发挥作用，并且还可用作抗病毒剂。本发明还涉及包含这些化合物的组合物，无论是用于体外使用还是用于治疗患有HCV感染的患者的给药，并涉及制备这些化合物的过程。本发明还涉及通过给予本发明化合物的组合物来治疗患有HCV感染的患者的方法。本发明还涉及制备这些化合物的过程。
• Inhibitors of serine proteases, particularly HCV NS3-NS4a protease
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP2341065A2

  公开（公告）日：2011-07-06

  The present invention relates to compounds of formula I or formula Ia or pharmaceutically acceptable salts thereof, that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease. As such, they act by interfering with the life cycle of the hepatitis C virus and are useful as antiviral agents. The invention further relates to pharmaceutically acceptable compositions comprising said compounds either for ex vivo use or for administration to a patient suffering from HCV infection and processes for preparing the compounds. The invention also relates to methods of treating an HCV infection in a patient by administering a pharmaceutical composition comprising a compound of this invention.

  本发明涉及抑制丝氨酸蛋白酶活性，特别是丙型肝炎病毒 NS3-NS4A 蛋白酶活性的式 I 或式 Ia 化合物或其药学上可接受的盐类。因此，它们通过干扰丙型肝炎病毒的生命周期发挥作用，可用作抗病毒药物。本发明还涉及包含上述化合物的药学上可接受的组合物，这些组合物可用于体内外使用，也可用于给丙型肝炎病毒感染患者用药，还涉及制备这些化合物的工艺。本发明还涉及通过施用包含本发明化合物的药物组合物治疗患者HCV感染的方法。
• PEPTIDES AS NS3-SERINE PROTEASE INHIBITORS OF HEPATITIS C VIRUS
  申请人：Schering Corporation

  公开号：EP1385870B1

  公开（公告）日：2010-03-17
• NOVEL PEPTIDES AS NS3-SERINE PROTEASE INHIBITORS OF HEPATITIS C VIRUS
  申请人：Schering Corporation

  公开号：EP1481000B1

  公开（公告）日：2010-06-02