(2S,3S)-3-amino-3-deutero-N-cyclopropyl-2-hydroxyhexanamide hydrochloric acid salt | 950842-32-7

• 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: (2S,3S)-3-amino-3-deutero-N-cyclopropyl-2-hydroxyhexanamide hydrochloric acid salt
• 英文别名: (2S,3S)-3-amino-3-deutero-N-cyclopropyl-2-hydroxyhexanamide hydrochloride；(2S,3S)-3-amino-N-cyclopropyl-3-deuterio-2-hydroxyhexanamide;hydrochloride
• CAS: 950842-32-7
• 化学式: C₉H₁₈N₂O₂*ClH
• 分子量: 223.707
• InChiKey: LMSDLVWKLIICSU-OHNJCESMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.18
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  75.4
• 氢给体数：
  4
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2S,3S)-3-amino-3-deutero-N-cyclopropyl-2-hydroxyhexanamide hydrochloric acid salt 、 (1S,3aR,6aS)-(2S)-2-环己基-N-(2-吡嗪基羰基)甘氨酰-3-甲基-L-缬氨酰八氢环戊并[c]吡咯-1-羧酸 在 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 生成 (1S,3aR,6aS)-N-((S)-3-deutero-1-(cyclopropylamino)-2-hydroxy-1-oxohexan-3-yl)-2-((S)-2-((S)-2-cyclohexyl-2-(pyrazine-2-carboxamido)acetamido)-3,3-dimethylbutanoyl)octahydrocyclopenta[c]pyrrole-1-carboxamide
  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
• 作为产物：
  描述：

  (2S,3S)-3-amino-3-deutero-N-cyclopropyl-2-hydroxyhexanamide deoxycholic acid salt 在 盐酸 作用下， 以 异丙醇 为溶剂， 反应 1.0h， 以75%的产率得到(2S,3S)-3-amino-3-deutero-N-cyclopropyl-2-hydroxyhexanamide hydrochloric acid salt
  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

• 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。