(+)-N-<<(2,2-dimethylcyclopropyl)carbonyl>oxy>succinimide | 107871-21-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (+)-N-<<(2,2-dimethylcyclopropyl)carbonyl>oxy>succinimide
• 英文别名: (S)-2,5-dioxopyrrolidin-1-yl 2,2-dimethylcyclopropanecarboxylate；2,5-dioxopyrrolidin-1-yl (S)-2,2-dimethylcyclopropane-1-carboxylate；(2,5-dioxopyrrolidin-1-yl) (1S)-2,2-dimethylcyclopropane-1-carboxylate
• CAS: 107871-21-6
• 化学式: C₁₀H₁₃NO₄
• 分子量: 211.218
• InChiKey: HVWKPGVEKOMRLV-ZCFIWIBFSA-N

物化性质

• 沸点：
  291.1±23.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.64
• 重原子数：
  15.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  63.68
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (+)-N-<<(2,2-dimethylcyclopropyl)carbonyl>oxy>succinimide 在 ammonium hydroxide 作用下， 以 乙醇 、 甲苯 为溶剂， 反应 0.75h， 生成 (Z)-8-Bromo-2-[((S)-2,2-dimethyl-cyclopropanecarbonyl)-amino]-oct-2-enoic acid
  参考文献：
  名称：

  Inhibition of the mammalian .beta.-lactamase renal dipeptidase (dehydropeptidase-I) by Z-2-(acylamino)-3-substituted-propenoic acids

  摘要：

  The title enzyme deactivates the potent carbapenem antibiotic imipenem in the kidney, producing low antibiotic levels in the urinary tract. A series of (Z)-2-(acylamino)-3-substituted-propenoic acids (3) are specific, competitive inhibitors of the enzyme capable of increasing the urinary concentration of imipenem in vivo. Many of the compounds were prepared in one step from an alpha-keto acid and a primary amide. The optimum R2 groups are 2,2-dimethyl, -dichloro, and -dibromocyclopropyl. With R2 = 2,2-dimethylcyclopropyl (DMCP), a wide variety of R3 groups including alkyl, oxa- and thiaalkyl, and alkyl groups containing acidic, basic, and neutral substituents give effective inhibitors with Ki values of 0.02-1 microM and a range of pharmacokinetic properties. By resolution of enantiomers and X-ray crystallography, the enzyme-inhibitory activity of the DMCP group was found to reside with the 1S isomer. The cysteinyl compound 176 (cilastatin, MK-0791) has the desired pharmacological properties and has been chosen for combination with imipenem.

  DOI：

  10.1021/jm00389a018
• 作为产物：
  描述：

  2,2-二甲基环丙烯羧酸 在 吡啶 作用下， 反应 1.5h， 生成 (+)-N-<<(2,2-dimethylcyclopropyl)carbonyl>oxy>succinimide
  参考文献：
  名称：

  Inhibition of the mammalian .beta.-lactamase renal dipeptidase (dehydropeptidase-I) by Z-2-(acylamino)-3-substituted-propenoic acids

  摘要：

  The title enzyme deactivates the potent carbapenem antibiotic imipenem in the kidney, producing low antibiotic levels in the urinary tract. A series of (Z)-2-(acylamino)-3-substituted-propenoic acids (3) are specific, competitive inhibitors of the enzyme capable of increasing the urinary concentration of imipenem in vivo. Many of the compounds were prepared in one step from an alpha-keto acid and a primary amide. The optimum R2 groups are 2,2-dimethyl, -dichloro, and -dibromocyclopropyl. With R2 = 2,2-dimethylcyclopropyl (DMCP), a wide variety of R3 groups including alkyl, oxa- and thiaalkyl, and alkyl groups containing acidic, basic, and neutral substituents give effective inhibitors with Ki values of 0.02-1 microM and a range of pharmacokinetic properties. By resolution of enantiomers and X-ray crystallography, the enzyme-inhibitory activity of the DMCP group was found to reside with the 1S isomer. The cysteinyl compound 176 (cilastatin, MK-0791) has the desired pharmacological properties and has been chosen for combination with imipenem.

  DOI：

  10.1021/jm00389a018

文献信息

• [EN] CDK2 INHIBITORS AND METHODS OF USING THE SAME<br/>[FR] INHIBITEURS DE CDK2 ET LEURS PROCÉDÉS D'UTILISATION
  申请人：CEDILLA THERAPEUTICS INC

  公开号：WO2022165513A1

  公开（公告）日：2022-08-04

  The present disclosure provides compounds, compositions thereof, and methods of using the same for the inhibition of CDK2, and the treatment of CDK2 related diseases and disorders.

  本公开提供了抑制CDK2的化合物、其组合物以及使用它们治疗CDK2相关疾病和疾病的方法。