(2S,4R)-4-(2-trifluoromethylbenzenesulfonyl)-2-(1-cyanocyclopropylcarbamoyl)-N-Boc-pyrrolidine | 1252632-25-9

• 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,4R)-4-(2-trifluoromethylbenzenesulfonyl)-2-(1-cyanocyclopropylcarbamoyl)-N-Boc-pyrrolidine
• 英文别名: (2S,4R)-2-(1-cyano-cyclopropylcarbamoyl)-4-(2-trifluoromethyl-benzenesulfonyl)-pyrrolidine-1-carboxylic acid t-butyl ester；(2S,4R)-2-(1-cyanocyclopropylcarbamoyl)-4-(2-trifluoromethylbenzenesulfonyl)pyrrolidine-1-carboxylic acid t-butyl ester；tert-butyl (2S,4R)-2-[(1-cyanocyclopropyl)carbamoyl]-4-[2-(trifluoromethyl)phenyl]sulfonylpyrrolidine-1-carboxylate
• CAS: 1252632-25-9
• 化学式: C₂₁H₂₄F₃N₃O₅S
• 分子量: 487.5
• InChiKey: OZYYWHFZTWCSKJ-HIFRSBDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2S,4R)-4-(2-trifluoromethylbenzenesulfonyl)-2-(1-cyanocyclopropylcarbamoyl)-N-Boc-pyrrolidine 、 三氟乙酸 以 二氯甲烷 为溶剂， 以97%的产率得到(2S,4R)-4-(2-trifluoromethylbenzenesulfonyl)-2-(1-cyanocyclopropylcarbamoyl)pyrrolidine trifluoroacetic acid
  参考文献：
  名称：

  Identification of Potent and Selective Cathepsin S Inhibitors Containing Different Central Cyclic Scaffolds

  摘要：

  Starting from the weakly active dual CatS/K inhibitor 5, structure-based design supported by X-ray analysis led to the discovery of the potent and selective (>50 000-fold vs CatK) cyclopentane derivative 22 by exploiting specific ligand-receptor interactions in the S2 pocket of CatS. Changing the central cyclopentane scaffold to the analogous pyrrolidine derivative 57 decreased the enzyme as well as the cell-based activity significantly by 24- and 69-fold, respectively. The most promising scaffold identified was the readily accessible proline derivative (e.g., 79). This compound, with an appealing ligand efficiency (LE) of 0.47, included additional structural modifications binding in the Si and S3 pockets of CatS, leading to favorable in vitro and in vivo properties. Compound 79 reduced IL-2 production in a transgenic DO10.11 mouse model of antigen presentation in a dose-dependent manner with an ED50 of 5 mg/kg.

  DOI：

  10.1021/jm401528k
• 作为产物：
  描述：

  N-Boc-顺式-4-羟基-L-脯氨酸甲酯 在 N-甲基吗啉 、 水 、 sodium hydride 、 三乙胺 、 间氯过氧苯甲酸 、 lithium hydroxide 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 mineral oil 为溶剂， 反应 0.5h， 生成 (2S,4R)-4-(2-trifluoromethylbenzenesulfonyl)-2-(1-cyanocyclopropylcarbamoyl)-N-Boc-pyrrolidine
  参考文献：
  名称：

  Identification of Potent and Selective Cathepsin S Inhibitors Containing Different Central Cyclic Scaffolds

  摘要：

  Starting from the weakly active dual CatS/K inhibitor 5, structure-based design supported by X-ray analysis led to the discovery of the potent and selective (>50 000-fold vs CatK) cyclopentane derivative 22 by exploiting specific ligand-receptor interactions in the S2 pocket of CatS. Changing the central cyclopentane scaffold to the analogous pyrrolidine derivative 57 decreased the enzyme as well as the cell-based activity significantly by 24- and 69-fold, respectively. The most promising scaffold identified was the readily accessible proline derivative (e.g., 79). This compound, with an appealing ligand efficiency (LE) of 0.47, included additional structural modifications binding in the Si and S3 pockets of CatS, leading to favorable in vitro and in vivo properties. Compound 79 reduced IL-2 production in a transgenic DO10.11 mouse model of antigen presentation in a dose-dependent manner with an ED50 of 5 mg/kg.

  DOI：

  10.1021/jm401528k

文献信息

• NOVEL PROLINE DERIVATIVES
  申请人：Sánchez Rubén Alvarez

  公开号：US20100267722A1

  公开（公告）日：2010-10-21

  The invention relates to a compound of formula (I) wherein A, R 1 -R 6 are as defined in the description and in the claims. The compound of formula (I) can be used as a medicament.

  这项发明涉及一种化合物，其化学式为（I），其中A，R1-R6如描述和权利要求中所定义。化合物的化学式（I）可用作药物。
• PROLINE DERIVATIVES AS CATHEPSIN INHIBITORS
  申请人：F.Hoffmann-La Roche AG

  公开号：EP2421826B1

  公开（公告）日：2013-10-23
• US8163793B2
  申请人：——

  公开号：US8163793B2

  公开（公告）日：2012-04-24