(1R,2R)-2-(morpholine-4-carbonyl)-4-oxocyclopentanecarboxylic acid ethyl ester | 1258451-13-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (1R,2R)-2-(morpholine-4-carbonyl)-4-oxocyclopentanecarboxylic acid ethyl ester
• 英文别名: (1R,2R)-2-(morpholine-4-carbonyl)-4-oxo-cyclopentanecarboxylic acid ethyl ester；ethyl (1R,2R)-2-(morpholine-4-carbonyl)-4-oxocyclopentane-1-carboxylate
• CAS: 1258451-13-6
• 化学式: C₁₃H₁₉NO₅
• 分子量: 269.298
• InChiKey: UFINVRUTLCRTST-GHMZBOCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  72.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R,2R)-2-(morpholine-4-carbonyl)-4-oxocyclopentanecarboxylic acid ethyl ester 在 2-吗啉乙磺酸 、 magnesium(II) chloride hexahydrate 、 葡萄糖 、 glucose dehydrogenase 102 、 ketoreductase NADP-131 、 nicotinamide adenine dinucleotide phosphate 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 21.0h， 生成 (1R,2R,4R)-4-methanesulfonyloxy-2-(morpholine-4-carbonyl)cyclopentanecarboxylic acid ethyl ester
  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：

  (+/-)-trans-4-Oxo-1,2-cyclopentanedicarboxylic acid diethyl ester 在 2-吗啉乙磺酸 、 lipase from Candida antarctica B 、 magnesium(II) acetate tetrahydrate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 42.0h， 生成 (1R,2R)-2-(morpholine-4-carbonyl)-4-oxocyclopentanecarboxylic acid ethyl ester
  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 CYCLOPENTANE DERIVATIVES
  申请人：Banner David

  公开号：US20100317647A1

  公开（公告）日：2010-12-16

  The invention relates to a compound of formula (I) wherein A 1 and R 1 to R 5 are defined as 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A1和R1至R5的定义如描述和权利要求中所述。化合物的化学式（I）可用作药物。
• Cyclopentane derivatives
  申请人：Hoffman-La Roche Inc.

  公开号：US07893099B2

  公开（公告）日：2011-02-22

  The invention relates to a compound of formula (I) wherein A1 and R1 to R5 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

  本发明涉及一种化合物，其化学式为（I），其中A1和R1至R5如说明书和权利要求中所定义。化合物（I）可用作药物。
• US7893099B2
  申请人：——

  公开号：US7893099B2

  公开（公告）日：2011-02-22
• Identification of Potent and Selective Cathepsin S Inhibitors Containing Different Central Cyclic Scaffolds
  作者：Hans Hilpert、Harald Mauser、Roland Humm、Lilli Anselm、Holger Kuehne、Guido Hartmann、Sabine Gruener、David W. Banner、Joerg Benz、Bernard Gsell、Andreas Kuglstatter、Martine Stihle、Ralf Thoma、Rubén Alvarez Sanchez、Hans Iding、Beat Wirz、Wolfgang Haap

  DOI：10.1021/jm401528k

  日期：2013.12.12

  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.