N-tert-butoxycarbonyl-N’-[N-(6-tert-butoxycarbonylaminohexyl)aminocarbonyl]-S-methylisothiourea | 1432471-10-7

• 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-tert-butoxycarbonyl-N’-[N-(6-tert-butoxycarbonylaminohexyl)aminocarbonyl]-S-methylisothiourea
• 英文别名: N-tert-butoxycarbonyl-N′-[N-(6-tert-butoxycarbonylaminohexyl)aminocarbonyl]-S-methylisothiourea；N-tert-butoxycarbonyl-N'-[N-(tert-butoxycarbonyl)-6-aminohexyl]aminocarbonyl-S-methylisothiourea
• CAS: 1432471-10-7
• 化学式: C₁₉H₃₆N₄O₅S
• 分子量: 432.585
• InChiKey: ISIPQAOXTUVCQT-UHFFFAOYSA-N

物化性质

• 密度：
  1.13±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.02
• 重原子数：
  29.0
• 可旋转键数：
  7.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.79
• 拓扑面积：
  118.12
• 氢给体数：
  3.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  N-tert-butoxycarbonyl-N’-[N-(6-tert-butoxycarbonylaminohexyl)aminocarbonyl]-S-methylisothiourea 在 三乙胺 、 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 18.0h， 生成 (2S)-N^ω-[(4-aminohexyl)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：

  2-甲基-2-丙基[(甲硫基)亚氨代甲酰基]氨基甲酸酯 、 tert-butyl N-[6-[(2,5-dioxopyrrolidin-1-yl)oxycarbonylamino]hexyl]carbamate 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以45%的产率得到N-tert-butoxycarbonyl-N’-[N-(6-tert-butoxycarbonylaminohexyl)aminocarbonyl]-S-methylisothiourea
  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

文献信息

• Discovery of a G Protein-Biased Radioligand for the Histamine H₂ Receptor with Reversible Binding Properties
  作者：Katharina Tropmann、Carina Höring、Nicole Plank、Steffen Pockes

  DOI：10.1021/acs.jmedchem.0c01494

  日期：2020.11.12

  synthesis and the chemical and pharmacological characterization of the highly stable carbamoylguanidine-type radioligand [3H]UR-KAT479 ([3H]23), a subtype selective histamine H2 receptor G protein-biased agonist. [3H]23 was characterized by saturation, kinetic, and competition binding assays at the human, guinea pig, and mouse H2 receptors (co-)expressed in HEK293(T) cells. [3H]23 reversibly bound to the

  当前使用的组胺H 2受体（H 2 R）放射性配体具有几个缺点，例如，高非特异性，难以克服的结合或半衰期短。我们报告了高度稳定的氨基甲酰基胍型放射性配体[ 3 H] UR-KAT479（[ 3 H] 23），一种亚型选择性组胺H 2受体G蛋白偏向激动剂的合成以及化学和药理学表征。[ 3 H] 23的特征在于在HEK293（T）细胞中表达的人类，豚鼠和小鼠H 2受体（共同）的饱和，动力学和竞争结合试验。[ 3小时] 23以中等至高亲和力（人/豚鼠/小鼠K d：24/28/94 nM）可逆地结合至各个H 2 Rs 。为了研究氨基甲酰基胍类配体在动物研究中阐明H 2 R在脑中的作用的适用性，我们在全人/小鼠血液中进行了初步分配实验，这表明[ 3 H]的结合很低23到红细胞。这些特性使[ 3 H] 23成为测定结合亲和力的有力工具，并证明了氨基甲酰基胍型配体的药代动力学前景。
• 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.