2-(3-Methoxyphenyl)butanoyl chloride | 1362736-09-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(3-Methoxyphenyl)butanoyl chloride
• CAS: 1362736-09-1
• 化学式: C₁₁H₁₃ClO₂
• 分子量: 212.676
• InChiKey: LZJAPUVWTPKKMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(3-Methoxyphenyl)butanoyl chloride 在 二甲基十二/十四烷基叔胺 作用下， 以 四氢呋喃 为溶剂， 反应 16.17h， 以42%的产率得到m-methoxyphenylethylketene
  参考文献：
  名称：

  Competitive Activity-Based Protein Profiling Identifies Aza-β-Lactams as a Versatile Chemotype for Serine Hydrolase Inhibition

  摘要：

  Serine hydrolases are one of the largest and most diverse enzyme classes in Nature. Most serine hydrolases lack selective inhibitors, which are valuable probes for assigning functions to these enzymes. We recently discovered a set of aza-beta-lactams (ABLs) that act as potent and selective inhibitors of the mammalian serine hydrolase protein-phosphatase methylesterase-1 (PME-1). The ABLs inactivate PME-1 by covalent acylation of the enzyme's serine nucleophile, suggesting that they could offer a general scaffold for serine hydrolase inhibitor discovery. Here, we have tested this hypothesis by screening ABLs more broadly against cell and tissue proteomes by competitive activity-based protein profiling (ABPP), leading to the discovery of lead inhibitors for several serine hydrolases, including the uncharacterized enzyme alpha,beta-hydrolase domain-containing 10 (ABHD10). ABPP-guided medicinal chemistry yielded a compound ABL303 that potently (IC50 approximate to 30 nM) and selectively inactivated ABHD10 in vitro and in living cells. A comparison of optimized inhibitors for PME-1 and ABHD10 indicates that modest structural changes that alter steric bulk can tailor the ABL to selectively react with distinct, distantly related serine hydrolases. Our findings, taken together, designate the ABL as a versatile reactive group for creating first-in-class serine hydrolase inhibitors.

  DOI：

  10.1021/ja300799t
• 作为产物：
  描述：

  3-甲氧基苯乙酸 在 正丁基锂 、 氯化亚砜 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 17.33h， 生成 2-(3-Methoxyphenyl)butanoyl chloride
  参考文献：
  名称：

  Competitive Activity-Based Protein Profiling Identifies Aza-β-Lactams as a Versatile Chemotype for Serine Hydrolase Inhibition

  摘要：

  Serine hydrolases are one of the largest and most diverse enzyme classes in Nature. Most serine hydrolases lack selective inhibitors, which are valuable probes for assigning functions to these enzymes. We recently discovered a set of aza-beta-lactams (ABLs) that act as potent and selective inhibitors of the mammalian serine hydrolase protein-phosphatase methylesterase-1 (PME-1). The ABLs inactivate PME-1 by covalent acylation of the enzyme's serine nucleophile, suggesting that they could offer a general scaffold for serine hydrolase inhibitor discovery. Here, we have tested this hypothesis by screening ABLs more broadly against cell and tissue proteomes by competitive activity-based protein profiling (ABPP), leading to the discovery of lead inhibitors for several serine hydrolases, including the uncharacterized enzyme alpha,beta-hydrolase domain-containing 10 (ABHD10). ABPP-guided medicinal chemistry yielded a compound ABL303 that potently (IC50 approximate to 30 nM) and selectively inactivated ABHD10 in vitro and in living cells. A comparison of optimized inhibitors for PME-1 and ABHD10 indicates that modest structural changes that alter steric bulk can tailor the ABL to selectively react with distinct, distantly related serine hydrolases. Our findings, taken together, designate the ABL as a versatile reactive group for creating first-in-class serine hydrolase inhibitors.

  DOI：

  10.1021/ja300799t

文献信息

• JPS58113156A
  申请人：——

  公开号：JPS58113156A

  公开（公告）日：1983-07-05
• US4753674A
  申请人：——

  公开号：US4753674A

  公开（公告）日：1988-06-28
• [EN] AlphaZetaAlpha-beta-LACTAM COMPOUNDS AND METHODS OF USING<br/>[FR] COMPOSÉS AZA-Beta-LACTAMES ET PROCÉDÉS D'UTILISATION
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2013152272A1

  公开（公告）日：2013-10-10

  The invention is directed to methods of modulation of serine hydrolase ABHD10, which can be selective with respect to other serine hydrolases such as PME-1. The compounds of the invention, or compounds useful in practice of a method of the invention, are aza-β-lactams, of which the (R)-enantiomer is preferred, for modulation of ABHD10. Methods of preparation are provided comprising the cycloaddition of dialkylazodicarboxylates with ketenes using the catalyst PPY*. The invention provides methods of treatment of conditions in patients for which modulation of ABHD10 is indicated, including pain, inflammation, metabolic disorders, solid tumors, or obesity.
• [EN] INHIBITORS OF MOLLUSCUM CONTAGIOSUM INFECTION AND METHODS USING THE SAME<br/>[FR] INHIBITEURS DE L'INFECTION PAR LE MOLLUSCUM CONTAGIOSUM ET MÉTHODES LES UTILISANT
  申请人：[en]THE TRUSTEES OF THE UNIVERSITY OF PENNSYLVANIA

  公开号：WO2023049919A1

  公开（公告）日：2023-03-30

  The present invention provides novel compounds, compositions and methods for treating, ameliorating, and/or preventing an orthopoxvirus infection in a subject in need thereof. In certain embodiments, the orthopoxvirus infection is caused byMolluscum contagiosum.
• Competitive Activity-Based Protein Profiling Identifies Aza-β-Lactams as a Versatile Chemotype for Serine Hydrolase Inhibition
  作者：Andrea M. Zuhl、Justin T. Mohr、Daniel A. Bachovchin、Sherry Niessen、Ku-Lung Hsu、Jacob M. Berlin、Maximilian Dochnahl、María P. López-Alberca、Gregory C. Fu、Benjamin F. Cravatt

  DOI：10.1021/ja300799t

  日期：2012.3.21

  Serine hydrolases are one of the largest and most diverse enzyme classes in Nature. Most serine hydrolases lack selective inhibitors, which are valuable probes for assigning functions to these enzymes. We recently discovered a set of aza-beta-lactams (ABLs) that act as potent and selective inhibitors of the mammalian serine hydrolase protein-phosphatase methylesterase-1 (PME-1). The ABLs inactivate PME-1 by covalent acylation of the enzyme's serine nucleophile, suggesting that they could offer a general scaffold for serine hydrolase inhibitor discovery. Here, we have tested this hypothesis by screening ABLs more broadly against cell and tissue proteomes by competitive activity-based protein profiling (ABPP), leading to the discovery of lead inhibitors for several serine hydrolases, including the uncharacterized enzyme alpha,beta-hydrolase domain-containing 10 (ABHD10). ABPP-guided medicinal chemistry yielded a compound ABL303 that potently (IC50 approximate to 30 nM) and selectively inactivated ABHD10 in vitro and in living cells. A comparison of optimized inhibitors for PME-1 and ABHD10 indicates that modest structural changes that alter steric bulk can tailor the ABL to selectively react with distinct, distantly related serine hydrolases. Our findings, taken together, designate the ABL as a versatile reactive group for creating first-in-class serine hydrolase inhibitors.