methyl 1-(furan-2-ylmethyl)-5-oxopyrrolidine-3-carboxylate | 893750-68-0

• 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-(furan-2-ylmethyl)-5-oxopyrrolidine-3-carboxylate
• CAS: 893750-68-0
• 化学式: C₁₁H₁₃NO₄
• mdl: MFCD06804428
• 分子量: 223.229
• InChiKey: IXRNMONLELHQRD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.454
• 拓扑面积：
  59.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 1-(furan-2-ylmethyl)-5-oxopyrrolidine-3-carboxylate 在 水 、 potassium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以75%的产率得到1-(2-呋喃甲基)-5-氧吡咯烷-3-羧酸
  参考文献：
  名称：

  Inhibition of noroviruses by piperazine derivatives

  摘要：

  There is currently an unmet need for the development of small-molecule therapeutics for norovirus infection. The piperazine scaffold, a privileged structure embodied in many pharmacological agents, was used to synthesize an array of structurally-diverse derivatives which were screened for anti-norovius activity in a cell-based replicon system. The studies described herein demonstrate for the first time that functionalized piperazine derivatives possess anti-norovirus activity. Furthermore, these studies have led to the identification of two promising compounds (6a and 9I) that can be used as a launching pad for the optimization of potency, cytotoxicity, and drug-like characteristics. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.122
• 作为产物：
  描述：

  2-呋喃甲胺 、 衣康酸二甲酯 生成 methyl 1-(furan-2-ylmethyl)-5-oxopyrrolidine-3-carboxylate
  参考文献：
  名称：

  Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor

  摘要：

  Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by la and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.10.053

文献信息

• 10.1021/acs.jmedchem.4c00551
  作者：Dampalla, Chamandi S.、Kim, Yunjeong、Zabiegala, Alexandria、Howard, Dennis J.、Nguyen, Harry Nhat、Madden, Trent K.、Thurman, Hayden A.、Cooper, Anne、Liu, Lijun、Battaile, Kevin P.、Lovell, Scott、Chang, Kyeong-Ok、Groutas, William C.

  DOI：10.1021/acs.jmedchem.4c00551

  日期：——

  Zoonotic coronaviruses are known to produce severe infections in humans and have been the cause of significant morbidity and mortality worldwide. SARS-CoV-2 was the largest and latest contributor of fatal cases, even though MERS-CoV has the highest case-fatality ratio among zoonotic coronaviruses. These infections pose a high risk to public health worldwide warranting efforts for the expeditious discovery

  众所周知，人畜共患冠状病毒会在人类中产生严重感染，并已成为全世界重大发病率和死亡率的原因。尽管中东呼吸综合征冠状病毒在人畜共患冠状病毒中病死率最高，但 SARS-CoV-2 是造成死亡病例的最大和最新的原因。这些感染对全世界的公共卫生构成了很高的风险，需要努力迅速发现抗病毒药物。因此，我们在此描述了一系列新型冠状病毒 3CL pro抑制剂，其中包含N-取代的 2-吡咯烷酮支架，设想利用与 S3-S4 亚位点的有利相互作用，并连接到不变的 Leu-Gln P 2-P1 识别元件。几种抑制剂在酶和基于细胞的测定中显示出纳摩尔级的抗病毒活性，并且没有明显的细胞毒性。确定与 3CL pro结合的抑制剂的高分辨率晶体结构，以探测和鉴定与结合相关的分子决定因素，为抑制剂的结构指导优化提供信息，并确认抑制剂的作用机制。
• Discovery of an orally efficaceous 4-phenoxypyrrolidine-based BACE-1 inhibitor
  作者：U. Iserloh、J. Pan、A.W. Stamford、M.E. Kennedy、Q. Zhang、L. Zhang、E.M. Parker、N.A. McHugh、L. Favreau、C. Strickland、J. Voigt

  DOI：10.1016/j.bmcl.2007.10.053

  日期：2008.1

  Based on a lead compound identified from the patent literature, we developed patentably novel BACE-1 inhibitors by introducing a cyclic amine scaffold as embodied by la and 1b. Extensive SAR studies assessed a variety of isophthalamide replacements including substituted pyrrolidinones and ultimately led to the identification of 11. Due to its favorable overall profile, 11 has been extensively profiled in various in vivo settings. (c) 2007 Elsevier Ltd. All rights reserved.
• Inhibition of noroviruses by piperazine derivatives
  作者：Dengfeng Dou、Guijia He、Sivakoteswara Rao Mandadapu、Sridhar Aravapalli、Yunjeong Kim、Kyeong-Ok Chang、William C. Groutas

  DOI：10.1016/j.bmcl.2011.10.122

  日期：2012.1

  There is currently an unmet need for the development of small-molecule therapeutics for norovirus infection. The piperazine scaffold, a privileged structure embodied in many pharmacological agents, was used to synthesize an array of structurally-diverse derivatives which were screened for anti-norovius activity in a cell-based replicon system. The studies described herein demonstrate for the first time that functionalized piperazine derivatives possess anti-norovirus activity. Furthermore, these studies have led to the identification of two promising compounds (6a and 9I) that can be used as a launching pad for the optimization of potency, cytotoxicity, and drug-like characteristics. (C) 2011 Elsevier Ltd. All rights reserved.