tert-butyl N-[6-[(2,5-dioxopyrrolidin-1-yl)oxycarbonylamino]hexyl]carbamate | 401792-94-7

• 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: tert-butyl N-[6-[(2,5-dioxopyrrolidin-1-yl)oxycarbonylamino]hexyl]carbamate
• CAS: 401792-94-7
• 化学式: C₁₆H₂₇N₃O₆
• 分子量: 357.407
• InChiKey: KQTQUAPEZDVTKG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  25
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[6-[(2,5-dioxopyrrolidin-1-yl)oxycarbonylamino]hexyl]carbamate 在 水 、 三乙胺 、 N,N-二异丙基乙胺 、 mercury dichloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (2S)-5-[[amino-(6-aminohexylcarbamoylamino)methylidene]amino]-N-[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]-2-[[2-[1-[2-oxo-2-[4-(6-oxo-5,11-dihydrobenzo[c][1]benzazepin-11-yl)piperazin-1-yl]ethyl]cyclopentyl]acetyl]amino]pentanamide;2,2,2-trifluoroacetic acid
  参考文献：
  名称：

  Dimeric argininamide-type neuropeptide Y receptor antagonists: Chiral discrimination between Y1 and Y4 receptors

  摘要：

  The structurally related peptides neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) are endogenous agonists of the NPY receptor (YR) family, which in humans comprises four functionally expressed subtypes, designated Y1R, Y2R, Y4R and Y5R. Nonpeptide antagonists with high affinity and selectivity have been described for the Y1R, Y2R and Y5R, but such compounds are still lacking for the Y4R. In this work, the structures of the high affinity selective (R)-argininamide-type Y1R antagonists BIBP3226 and BIBO3304 were linked via the guanidine or urea moieties to give homo-dimeric argininamides with linker lengths ranging from 31 to 41 atoms. Interestingly, the twin compounds proved to be by far less selective for the Y1R than the R-configured monovalent parent compounds. The decrease in selectivity ratio was most pronounced for Y1R versus Y4R subtype, resulting in comparable affinities of bivalent ligands for Y1R and Y4R (e.g. UR-MK177 ((R, R)-49): K-i = 230 nM (Y1R) and 290 nM (Y4R)). With a Ki value of 130 nM and a K-b value of 20 nM, UR-MK188 ((R,R)-51) was superior to all Y4R antagonists known to date. The S, S-configured optical antipodes of UR-MK177 and UR-MK188 (UR-MEK381 ((S, S)-49) and UR-MEK388 ((S,S)-51)) were synthesized to investigate the stereochemical discrimination by the different receptor subtypes. Whereas preference for R, R-configured argininamides was characteristic of the Y1R, stereochemical discrimination by the Y4R was not observed. This may pave the way to selective Y4R antagonists. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.08.065

文献信息

• [³H]UR-PLN196: A Selective Nonpeptide Radioligand and Insurmountable Antagonist for the Neuropeptide Y Y₂ Receptor
  作者：Nikola Pluym、Paul Baumeister、Max Keller、Günther Bernhardt、Armin Buschauer

  DOI：10.1002/cmdc.201200566

  日期：2013.4

  Radioing in on NPY: Attachment of a [2,3‐3H]propionyl group through an appropriate linker to the guanidine group of an (S)‐argininamide‐type neuropeptide Y (NPY) Y2 receptor antagonist resulted in a subtype‐selective radioligand.

  Radioing在NPY：一个[2,3-的附件3通过适当的连接体与胍基的（的H]丙酰基小号）-argininamide型神经肽Y（NPY）Y 2受体拮抗剂导致了亚型选择性放射性配体。
• Dimeric argininamide-type neuropeptide Y receptor antagonists: Chiral discrimination between Y1 and Y4 receptors
  作者：Max Keller、Melanie Kaske、Tobias Holzammer、Günther Bernhardt、Armin Buschauer

  DOI：10.1016/j.bmc.2013.08.065

  日期：2013.11

  The structurally related peptides neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP) are endogenous agonists of the NPY receptor (YR) family, which in humans comprises four functionally expressed subtypes, designated Y1R, Y2R, Y4R and Y5R. Nonpeptide antagonists with high affinity and selectivity have been described for the Y1R, Y2R and Y5R, but such compounds are still lacking for the Y4R. In this work, the structures of the high affinity selective (R)-argininamide-type Y1R antagonists BIBP3226 and BIBO3304 were linked via the guanidine or urea moieties to give homo-dimeric argininamides with linker lengths ranging from 31 to 41 atoms. Interestingly, the twin compounds proved to be by far less selective for the Y1R than the R-configured monovalent parent compounds. The decrease in selectivity ratio was most pronounced for Y1R versus Y4R subtype, resulting in comparable affinities of bivalent ligands for Y1R and Y4R (e.g. UR-MK177 ((R, R)-49): K-i = 230 nM (Y1R) and 290 nM (Y4R)). With a Ki value of 130 nM and a K-b value of 20 nM, UR-MK188 ((R,R)-51) was superior to all Y4R antagonists known to date. The S, S-configured optical antipodes of UR-MK177 and UR-MK188 (UR-MEK381 ((S, S)-49) and UR-MEK388 ((S,S)-51)) were synthesized to investigate the stereochemical discrimination by the different receptor subtypes. Whereas preference for R, R-configured argininamides was characteristic of the Y1R, stereochemical discrimination by the Y4R was not observed. This may pave the way to selective Y4R antagonists. (C) 2013 Elsevier Ltd. All rights reserved.