(R)-特拉匹韦 | 923270-50-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 中文名称: (R)-特拉匹韦
• 英文名称: VRT-127394
• 英文别名: (R)-telaprevir；(1S,3aR,6aS)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)-N-((R)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl)octahydrocyclopenta[c]pyrrole-1-carboxamide；Telaprevir, (R)-；(3S,3aS,6aR)-2-[(2S)-2-[[(2S)-2-cyclohexyl-2-(pyrazine-2-carbonylamino)acetyl]amino]-3,3-dimethylbutanoyl]-N-[(3R)-1-(cyclopropylamino)-1,2-dioxohexan-3-yl]-3,3a,4,5,6,6a-hexahydro-1H-cyclopenta[c]pyrrole-3-carboxamide
• CAS: 923270-50-2
• 化学式: C₃₆H₅₃N₇O₆
• 分子量: 679.86
• InChiKey: BBAWEDCPNXPBQM-USXSPERKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  49
• 可旋转键数：
  14
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  180
• 氢给体数：
  4
• 氢受体数：
  8

安全信息

• 储存条件：
  | 2-8°C |

反应信息

• 作为产物：
  描述：

  特拉匹韦 以 乙腈 为溶剂， 反应 72.0h， 生成 (R)-特拉匹韦
  参考文献：
  名称：

  In Vitro and In Vivo Isotope Effects with Hepatitis C Protease Inhibitors: Enhanced Plasma Exposure of Deuterated Telaprevir versus Telaprevir in Rats

  摘要：

  Telaprevir 2 (VX-950), an inhibitor of the hepatitis C virus (HCVa) NS3-4A protease, is in phase 3 clinical trials. One of the major metabolites of 2 is its P1-(R)-diastereoisomer, 3 (VRT-394), containing an inversion at the chiral center next to the alpha-ketoamide on exchange of a proton with solvent. Compound 3 is approximately 30-fold less active against HCV protease. In an attempt to suppress the epimerization of 2 without losing activity against the HCV protease, the proton at that chiral site was replaced with deuterium (d). The compound 1 (d-telaprevir) is as efficacious as 2 in in vitro inhibition of protease activity and viral replication (replicon) assays. The kinetics of in vitro stability of 1 and 2 in buffered pH solutions and plasma samples, including human plasma, suggest that 1 is significantly more stable than 2. Oral administration (10 mg/kg) in rats resulted in a similar to 13% increase of AUC for 1.

  DOI：

  10.1021/jm901023f

文献信息

• Processes and intermediates
  申请人：Tanoury J. Gerald

  公开号：US20070087973A1

  公开（公告）日：2007-04-19

  The invention relates to compounds and processes useful for the preparation of protease inhibitors, particularly serine protease inhibitors. The protease inhibitors are useful for treatment of HCV infections.

  这项发明涉及到化合物和工艺，用于制备蛋白酶抑制剂，特别是丝氨酸蛋白酶抑制剂。这些蛋白酶抑制剂对治疗HCV感染很有用。
• [EN] DEGRADERS OF HEPATITIS C VIRUS NS3/4A PROTEIN<br/>[FR] AGENTS DE DÉGRADATION DE LA PROTÉINE NS3/4A DU VIRUS DE L'HÉPATITE C
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2020069125A1

  公开（公告）日：2020-04-02

  Disclosed are bifunctional compounds (degraders) that target hepatitis C virus (HCV) NS3/4A for degradation. Also disclosed are pharmaceutical compositions containing the degraders and methods of using the compounds to treat HCV infection and HCV-associated diseases or disorders.

  本文披露了针对丙型肝炎病毒（HCV）NS3/4A进行降解的双功能化合物（降解剂）。还披露了含有这些降解剂的药物组合物以及使用这些化合物治疗HCV感染和HCV相关疾病或紊乱的方法。
• Deuterated hepatitis C protease inhibitors
  申请人：Perni B. Robert

  公开号：US20070225297A1

  公开（公告）日：2007-09-27

  A deuterated α-ketoamido steric specific compound of the formula wherein D denotes a deuterium atom on a steric specific carbon atom.

  一种氘代的α-酮氨基立体特异化合物，其化学式为其中D表示立体特异碳原子上的一个氘原子。
• PROCESSES AND INTERMEDIATES
  申请人：Tanoury Gerald J.

  公开号：US20100063252A1

  公开（公告）日：2010-03-11

  The invention relates to compounds and processes useful for the preparation of protease inhibitors, particularly serine protease inhibitors. The protease inhibitors are useful for treatment of HCV infections.

  该发明涉及化合物和工艺，用于制备蛋白酶抑制剂，特别是丝氨酸蛋白酶抑制剂。这些蛋白酶抑制剂对治疗HCV感染很有用。
• Inhibitors of serine proteases
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP2256113A1

  公开（公告）日：2010-12-01

  This invention relates to a mixture of diastereomeric compounds of Formula I: or a pharmaceutically acceptable salt or mixtures thereof, wherein C* represents a diastereomeric carbon atom.

  本发明涉及一种式 I 非对映化合物混合物： 或其药学上可接受的盐或混合物，其中 C* 代表非对映碳原子。