methyl 1-benzyl-3-((3-ethoxy-3-oxopropanamido)methyl)pyrrolidine-3-carboxylate | 1312815-03-4

• 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: methyl 1-benzyl-3-((3-ethoxy-3-oxopropanamido)methyl)pyrrolidine-3-carboxylate
• 英文别名: Methyl 1-benzyl-3-((3-ethoxy-3-oxopropanamido)methyl)pyrrolidine-3-carboxylate；methyl 1-benzyl-3-[[(3-ethoxy-3-oxopropanoyl)amino]methyl]pyrrolidine-3-carboxylate
• CAS: 1312815-03-4
• 化学式: C₁₉H₂₆N₂O₅
• 分子量: 362.426
• InChiKey: PVOQJZRWLHCAQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  26
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  84.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  methyl 1-benzyl-3-((3-ethoxy-3-oxopropanamido)methyl)pyrrolidine-3-carboxylate 在 palladium 10% on activated carbon 、 氢气 、 sodium methylate 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 21.0h， 生成
  参考文献：
  名称：

  Novel ATP competitive MK2 inhibitors with potent biochemical and cell-based activity throughout the series

  摘要：

  Optimization of our previously described pyrrolopiperidone series led to the identification of a new benzamide sub-series, which exhibits consistently high potency in biochemical and cell-based assays throughout the series. Strong inhibition of LPS-induced production of the cytokine TNF alpha is coupled to the regulation of HSP27 phosphorylation, indicating that the observed cellular effects result from the inhibition of MK2. X-ray crystallographic and computational analyses provide a rationale for the high potency of the series. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.071
• 作为产物：
  描述：

  ethyl 1-benzyl-3-cyanopyrrolidine-3-carboxylate 在 氢气 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 methyl 1-benzyl-3-((3-ethoxy-3-oxopropanamido)methyl)pyrrolidine-3-carboxylate
  参考文献：
  名称：

  Novel ATP competitive MK2 inhibitors with potent biochemical and cell-based activity throughout the series

  摘要：

  Optimization of our previously described pyrrolopiperidone series led to the identification of a new benzamide sub-series, which exhibits consistently high potency in biochemical and cell-based assays throughout the series. Strong inhibition of LPS-induced production of the cytokine TNF alpha is coupled to the regulation of HSP27 phosphorylation, indicating that the observed cellular effects result from the inhibition of MK2. X-ray crystallographic and computational analyses provide a rationale for the high potency of the series. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.071

文献信息

• [EN] MK2 INHIBITORS<br/>[FR] INHIBITEURS DE MK2
  申请人：ORGANON NV

  公开号：WO2011073119A1

  公开（公告）日：2011-06-23

  The present invention relates to compounds of general Formula (I) or a pharmaceutically acceptable salt thereof. The compounds can be used in the treatment of immune, autoimmune, inflammatory diseases, cardiovascular diseases, infectious diseases, bone resorption disorders, neurodegenerative diseases or proliferative diseases.

  本发明涉及一般式（I）的化合物或其药用盐。这些化合物可用于治疗免疫、自身免疫、炎症性疾病、心血管疾病、传染病、骨吸收障碍、神经退行性疾病或增殖性疾病。
• MK2 INHIBITORS
  申请人：Merck Sharp & Dohme B.V.

  公开号：US20140288109A1

  公开（公告）日：2014-09-25

  The present invention relates to compounds of general Formula (I) or a pharmaceutically acceptable salt thereof. The compounds can be used in the treatment of immune, autoimmune, inflammatory diseases, cardiovascular diseases, infectious diseases, bone resorption disorders, neurodegenerative diseases or proliferative diseases.

  本发明涉及一般式（I）的化合物或其药学上可接受的盐。该化合物可用于治疗免疫、自身免疫、炎症性疾病、心血管疾病、传染病、骨吸收紊乱、神经退行性疾病或增生性疾病。
• MK2 inhibitors
  申请人：MERCK SHARP & DOHME B.V.

  公开号：US09102676B2

  公开（公告）日：2015-08-11

  The present invention relates to compounds of general Formula (I) or a pharmaceutically acceptable salt thereof. The compounds can be used in the treatment of immune, autoimmune, inflammatory diseases, cardiovascular diseases, infectious diseases, bone resorption disorders, neurodegenerative diseases or proliferative diseases.

  本发明涉及一般式（I）的化合物或其药学上可接受的盐。这些化合物可用于治疗免疫、自身免疫、炎症性疾病、心血管疾病、传染病、骨吸收障碍、神经退行性疾病或增生性疾病。
• US9102676B2
  申请人：——

  公开号：US9102676B2

  公开（公告）日：2015-08-11
• Novel ATP competitive MK2 inhibitors with potent biochemical and cell-based activity throughout the series
  作者：Arthur Oubrie、Allard Kaptein、Edwin de Zwart、Niels Hoogenboom、Rianne Goorden、Bas van de Kar、Maaike van Hoek、Vera de Kimpe、Ruud van der Heijden、Judith Borsboom、Bert Kazemier、Jeroen de Roos、Michiel Scheffers、Jos Lommerse、Carsten Schultz-Fademrecht、Tjeerd Barf

  DOI：10.1016/j.bmcl.2011.10.071

  日期：2012.1

  Optimization of our previously described pyrrolopiperidone series led to the identification of a new benzamide sub-series, which exhibits consistently high potency in biochemical and cell-based assays throughout the series. Strong inhibition of LPS-induced production of the cytokine TNF alpha is coupled to the regulation of HSP27 phosphorylation, indicating that the observed cellular effects result from the inhibition of MK2. X-ray crystallographic and computational analyses provide a rationale for the high potency of the series. (C) 2011 Elsevier Ltd. All rights reserved.