[4-(2,5-dioxo-pyrrolidin-1-yloxycarbonylamino)-butyl]-carbamic acid t-butyl ester | 404004-37-1

• 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: [4-(2,5-dioxo-pyrrolidin-1-yloxycarbonylamino)-butyl]-carbamic acid t-butyl ester
• 英文别名: tert-butyl N-[4-[(2,5-dioxopyrrolidin-1-yl)oxycarbonylamino]butyl]carbamate
• CAS: 404004-37-1
• 化学式: C₁₄H₂₃N₃O₆
• 分子量: 329.353
• InChiKey: XLYQODSXGANGRY-UHFFFAOYSA-N

物化性质

• 熔点：
  134-139 °C
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 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：

  [4-(2,5-dioxo-pyrrolidin-1-yloxycarbonylamino)-butyl]-carbamic acid t-butyl ester 在 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 、 mercury dichloride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 (2S)-N^ω-[(4-aminobutyl)aminocarbonyl]-N-[2-(3,5-dioxo-1,2-diphenyl-1,2,4-triazolidin-4-yl)ethyl]-N^α-[2-(1-{2-oxo-2-[4-(6-oxo-6,11-dihydro-5H-dibenzo[b,e]azepin-11-yl)piperazin-1-yl]ethyl}cyclopentyl)acetyl]argininamide
  参考文献：
  名称：

  [3H] UR-PLN196：神经肽Y Y2受体的选择性非肽放射性配体和不可克服的拮抗剂

  摘要：

  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。

  DOI：

  10.1002/cmdc.201200566
• 作为产物：
  描述：

  N,N'-二琥珀酰亚胺基碳酸酯 、 N-叔丁氧羰基-1,4-丁二胺 以 乙腈 为溶剂， 以75.1%的产率得到[4-(2,5-dioxo-pyrrolidin-1-yloxycarbonylamino)-butyl]-carbamic acid t-butyl ester
  参考文献：
  名称：

  β细胞特异性链脲佐菌素衍生的近红外成像探针的合成和测试。

  摘要：

  DOI：

  10.1002/anie.200702183

文献信息

• Application of the Guanidine-Acylguanidine Bioisosteric Approach to Argininamide-Type NPY Y2 Receptor Antagonists
  作者：Nikola Pluym、Albert Brennauer、Max Keller、Ralf Ziemek、Nathalie Pop、Günther Bernhardt、Armin Buschauer

  DOI：10.1002/cmdc.201100241

  日期：2011.9.5

  structural elements, but they compromise the drug‐likeness of numerous biologically active compounds, including ligands of G‐protein‐coupled receptors (GPCRs). As part of a project focused on the search for guanidine bioisosteres, argininamide‐type neuropeptide Y (NPY) Y2 receptor (Y2R) antagonists related to BIIE0246 were synthesized. Starting from ornithine derivatives, NG‐acylated argininamides were obtained

  诸如胍基等强碱性基团是至关重要的结构元素，但它们会损害许多生物活性化合物的药物样，包括G蛋白偶联受体（GPCR）的配体。作为致力于寻找胍类生物等位基因的项目的一部分，合成了与BIIE0246相关的精氨酸酰胺型神经肽Y（NPY）Y 2受体（Y 2 R）拮抗剂。从鸟氨酸衍生物开始，N ģ -acylated argininamides通过胍基化量身定做的单-Boc保护的得到Ñ -acyl-小号-methylisothioureas。研究了这些化合物的Y 2 R拮抗作用（钙测定），Y 2R亲和力和NPY受体亚型选择性（流式细胞术结合测定）。大多数N G取代的（S）-精氨酰胺显示出与母体化合物相似的Y 2 R拮抗活性和结合亲和力，而带有末端胺的N G酰化或氨基甲酰化类似物则更为出色（Y 2 R：K i和K B值在低纳摩尔范围内）。这表明化合物的碱性虽然比胍的碱度低4-5个数量级，但足以与Y 2的酸性氨基酸形成关键相互作用R
• 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.