(S)-3-Methyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyric acid | 319011-86-4

• 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: (S)-3-Methyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyric acid
• 英文别名: (2S)-3-methyl-2-[[(2S)-3-methyl-2-(pyrazine-2-carbonylamino)butanoyl]amino]butanoic acid
• CAS: 319011-86-4
• 化学式: C₁₅H₂₂N₄O₄
• 分子量: 322.364
• InChiKey: LGCWVJZMNKSSCX-RYUDHWBXSA-N

物化性质

• 沸点：
  634.7±55.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  121
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-3-Methyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyric acid 在 sodium hydroxide 、 N-羟基-7-氮杂苯并三氮唑 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N'-二环己基碳二亚胺 作用下， 以 乙醇 为溶剂， 生成 (1S,3aR,6aS)-2-((S)-3-Methyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyryl)-octahydro-cyclopenta[c]pyrrole-1-carboxylic acid [1-(cyclopropylcarbamoyl-hydroxy-methyl)-butyl]-amide
  参考文献：
  名称：

  Discovery of a novel bicycloproline P2 bearing peptidyl α-ketoamide LY514962 as HCV protease inhibitor

  摘要：

  We describe herein the design, syntheses and evaluation of a number of bicycloproline P2 bearing HCV protease inhibitors endowed with impressive enzyme potency, enzyme selectivity, cellular activity and favorable ADME profiles. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.074
• 作为产物：
  描述：

  D-Valyl-D-Valin-hydrochlorid 在 sodium hydroxide 、 氯化亚砜 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 作用下， 以 甲醇 为溶剂， 生成 (S)-3-Methyl-2-{(S)-3-methyl-2-[(pyrazine-2-carbonyl)-amino]-butyrylamino}-butyric acid
  参考文献：
  名称：

  Discovery of a novel bicycloproline P2 bearing peptidyl α-ketoamide LY514962 as HCV protease inhibitor

  摘要：

  We describe herein the design, syntheses and evaluation of a number of bicycloproline P2 bearing HCV protease inhibitors endowed with impressive enzyme potency, enzyme selectivity, cellular activity and favorable ADME profiles. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.074

文献信息

• INHIBITORS OF SERINE PROTEASE, PARTICULARLY HCV NS3-NS4A PROTEASE
  申请人：Farmer Luc J.

  公开号：US20090022688A1

  公开（公告）日：2009-01-22

  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 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.

  本发明涉及公式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，特别是丝氨酸蛋白酶NS3-NS4A的活性。因此，它们通过干扰丙型肝炎病毒的生命周期而起作用，并可用作抗病毒剂。本发明还涉及包含所述化合物的药学上可接受的组合物，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，以及制备这些化合物的过程。本发明还涉及通过给予本发明的化合物制成的药物组合物来治疗患有HCV感染的患者的方法。
• Peptidomimetic protease inhibitors
  申请人：Babine Robert Edward

  公开号：US20100137583A1

  公开（公告）日：2010-06-03

  The present invention relates to peptidomimetic compounds useful as protease inhibitors, particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel steroselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

  本发明涉及用作蛋白酶抑制剂的肽类模拟化合物，特别是丝氨酸蛋白酶抑制剂，更特别是丙型肝炎NS3蛋白酶抑制剂；其中间体；它们的制备，包括新的对中间体的立体选择性过程。本发明还涉及制药组合物和使用该化合物抑制HCV蛋白酶或治疗患有HCV感染或与感染相关的生理状况的患者的方法。还提供了药物组合物，其中包括除一种或多种HCV丝氨酸蛋白酶抑制剂外，还包括一种或多种表现出抗HCV活性的干扰素和/或一种或多种具有抗HCV活性的化合物和药学可接受载体，并使用该组合物治疗或预防患者的HCV感染的方法。本发明还涉及用于治疗或预防患者HCV感染的工具包或药品包。
• PEPTIDOMIMETIC PROTEASE INHIBITORS
  申请人：BABINE ROBERT EDWARD

  公开号：US20120282219A1

  公开（公告）日：2012-11-08

  The present invention relates to peptidomimetic compounds useful as protease inhibitors, particularly as serine protease inhibitors and more particularly as hepatitis C NS3 protease inhibitors; intermediates thereto; their preparation including novel stereoselective processes to intermediates. The invention is also directed to pharmaceutical compositions and to methods for using the compounds for inhibiting HCV protease or treating a patient suffering from an HCV infection or physiological condition related to the infection. Also provided are pharmaceutical combinations comprising, in addition to one or more HCV serine protease inhibitors, one or more interferons exhibiting anti-HCV activity and/or one or more compounds having anti HCV activity and a pharmaceutically acceptable carrier, and methods for treating or preventing a HCV infection in a patient using the compositions. The present invention is also directed to a kit or pharmaceutical pack for treating or preventing HCV infection in a patient.

  本发明涉及肽类似物化合物，作为蛋白酶抑制剂，特别是作为丝氨酸蛋白酶抑制剂，更特别是作为丙型肝炎NS3蛋白酶抑制剂；以及其中间体；它们的制备，包括新的对中间体的立体选择性过程。本发明还涉及制药组合物，以及使用这些化合物抑制HCV蛋白酶或治疗患有HCV感染或与感染相关的生理状况的患者的方法。还提供了药物组合物，其中除了一个或多个HCV丝氨酸蛋白酶抑制剂外，还包括一个或多个表现出抗HCV活性的干扰素和/或一个或多个具有抗HCV活性的化合物和一种药学上可接受的载体，并使用这些组合物来治疗或预防患者的HCV感染。本发明还涉及用于治疗或预防患者HCV感染的工具包或药物包。
• P1 and P3 optimization of novel bicycloproline P2 bearing tetrapeptidyl α-ketoamide based HCV protease inhibitors
  作者：Frantz Victor、Jason Lamar、Nancy Snyder、Yvonne Yip、Deqi Guo、Nathan Yumibe、Robert B. Johnson、Q.May Wang、John I. Glass、Shu-Hui Chen

  DOI：10.1016/j.bmcl.2003.09.075

  日期：2004.1

  With the aim of discovering potent and selective HCV protease inhibitors, we synthesized and evaluated a series of Ia based tetrapeptidyl ketoamides with additional modification(s) at P1', P1, and P3 positions. As a result of this effort, we found that replacement of the P3 valine with tert-leucine resulted in the discovery of a series of inhibitors (e.g., 3a, 3c, and 4c) endowed with improved enzyme and/or cellular activity relative to Ia. When dosed to F-344 rats orally at 50 mg/kg, 3a achieved 2.5 x higher liver and plasma exposure in comparison to that detected with 1a. (C) 2003 Elsevier Ltd. All rights reserved.
• INHIBITORS OF SERINE PROTEASES, PARTICULARLY HCV NS3-NS4A PROTEASE
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP1636208B1

  公开（公告）日：2012-02-29