N-(2-Oxo-tetrahydro-thiophen-3-yl)-3-phenyl-propionamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(2-Oxo-tetrahydro-thiophen-3-yl)-3-phenyl-propionamide
• 英文别名: N-(2-oxothiolan-3-yl)-3-phenylpropanamide
• 化学式: C₁₃H₁₅NO₂S
• 分子量: 249.334
• InChiKey: IXNNBHGXSHYBQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  71.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(2-Oxo-tetrahydro-thiophen-3-yl)-3-phenyl-propionamide 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以83%的产率得到4-Mercapto-2-(3-phenyl-propionylamino)-butyric acid
  参考文献：
  名称：

  Inhibition of Peptidylglycine .alpha.-Amidating Monooxygenase by N-Substituted Homocysteine Analogs

  摘要：

  C-terminal amidation is a posttranslational modification found in many neuropeptides. Peptidylglycine cl-amidating monooxygenase (PAM) catalyzes the synthesis of the biologically essential C-terminal amide from a glycine-extended precursor peptide. Reported herein are the first potent inhibitors of PAM. Dipeptides containing a C-terminal homocysteine and an N-acylated hydrophobic amino acid were found to inhibit PAM with IC(50)s in the low nanomolar range. Inhibition potency was dependent on both the carboxylate and the thiolate functionalities of the homocysteine and on the hydrophobic groups of the second amino acid. The thiolate was postulated to produce high binding affinities through coordination with the active-site copper. The compound series also exhibited potent inhibition of PAM in rat dorsal root ganglion cells as demonstrated by a dose-dependent increase in the substance P-Gly/substance P ratio. These results indicate that the compounds have sufficient potency and intracellular bioavailability to aid future studies focused on neuropeptide function and the contributions of neuropeptides to various disease processes.

  DOI：

  10.1021/jm00052a002
• 作为产物：
  描述：

  DL-高半胱氨酸硫内酯盐酸盐 、 3-苯基丙酸 在 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 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 N-(2-Oxo-tetrahydro-thiophen-3-yl)-3-phenyl-propionamide
  参考文献：
  名称：

  Inhibition of Peptidylglycine .alpha.-Amidating Monooxygenase by N-Substituted Homocysteine Analogs

  摘要：

  C-terminal amidation is a posttranslational modification found in many neuropeptides. Peptidylglycine cl-amidating monooxygenase (PAM) catalyzes the synthesis of the biologically essential C-terminal amide from a glycine-extended precursor peptide. Reported herein are the first potent inhibitors of PAM. Dipeptides containing a C-terminal homocysteine and an N-acylated hydrophobic amino acid were found to inhibit PAM with IC(50)s in the low nanomolar range. Inhibition potency was dependent on both the carboxylate and the thiolate functionalities of the homocysteine and on the hydrophobic groups of the second amino acid. The thiolate was postulated to produce high binding affinities through coordination with the active-site copper. The compound series also exhibited potent inhibition of PAM in rat dorsal root ganglion cells as demonstrated by a dose-dependent increase in the substance P-Gly/substance P ratio. These results indicate that the compounds have sufficient potency and intracellular bioavailability to aid future studies focused on neuropeptide function and the contributions of neuropeptides to various disease processes.

  DOI：

  10.1021/jm00052a002

文献信息

• 6-ACETYLMORPHINE ANALOGS, AND METHODS FOR THEIR SYNTHESIS AND USE
  申请人：Alere San Diego, Inc.

  公开号：EP3470416A1

  公开（公告）日：2019-04-17

  The present invention relates to novel 6-acetylmorphine analogs, and methods for their synthesis and use. Such analogs are designed to provide a convenient linkage chemistry for coupling under mild conditions to a suitable group on a target protein, polypeptide, solid phase or detectable label.

  本发明涉及新型 6-乙酰吗啡类似物及其合成和使用方法。此类类似物旨在提供方便的连接化学反应，以便在温和条件下与目标蛋白质、多肽、固相或可检测标签上的适当基团偶联。