tert-butyl N-[N-[(2-methylpropan-2-yl)oxycarbonyl]-N'-[3-[[1-(2-phenylethyl)piperidin-4-yl]-propanoylamino]propyl]carbamimidoyl]carbamate | 439099-20-4

• 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: tert-butyl N-[N-[(2-methylpropan-2-yl)oxycarbonyl]-N'-[3-[[1-(2-phenylethyl)piperidin-4-yl]-propanoylamino]propyl]carbamimidoyl]carbamate
• CAS: 439099-20-4
• 化学式: C₃₀H₄₉N₅O₅
• 分子量: 559.75
• InChiKey: AAKSRQWMQIJJLY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  40
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[N-[(2-methylpropan-2-yl)oxycarbonyl]-N'-[3-[[1-(2-phenylethyl)piperidin-4-yl]-propanoylamino]propyl]carbamimidoyl]carbamate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 N-(3-Guanidino-propyl)-N-(1-phenethyl-piperidin-4-yl)-propionamide
  参考文献：
  名称：

  Fentanyl derivatives bearing aliphatic alkaneguanidinium moieties: a new series of hybrid molecules with significant binding affinity for μ-opioid receptors and I2-imidazoline binding sites

  摘要：

  A new series of fentanyl derivatives [i.e., N-[1-(2-phenethyl)-4-piperidyl]-N-(guanidinoalkyl)propanamide] bearing aliphatic alkaneguanidinium moieties were prepared. Their affinities for the V opioid receptors and for the I-2-imidazoline binding sites (I-2-IBS) were determined on human post-mortem prefrontal cortex membranes. All of these hybrid compounds had significant and/or very high affinity for both receptors in the nanomolar range, meaning an improvement compared to the prototype N-[1-(2-phenethyl)-4-piperidyl]-N-(guanidinopropyl)propanamide previously reported. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.048
• 作为产物：
  描述：

  [3-(1-Phenethyl-piperidin-4-ylamino)-propyl]-carbamic acid benzyl ester 在 palladium on activated charcoal TEA 、 氢气 、 mercury dichloride 作用下， 以 甲醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 20.0 ℃ 、275.79 kPa 条件下， 反应 34.0h， 生成 tert-butyl N-[N-[(2-methylpropan-2-yl)oxycarbonyl]-N'-[3-[[1-(2-phenylethyl)piperidin-4-yl]-propanoylamino]propyl]carbamimidoyl]carbamate
  参考文献：
  名称：

  Guanidinium and aminoimidazolinium derivatives of N-(4-piperidyl)propanamides as potential ligands for μ opioid and I2-imidazoline receptors: synthesis and pharmacological screening

  摘要：

  Derivatives of N-(1-phenethyl-4-piperidyl)propanamides incorporating guanidinium and 2-aminoimidazolinium groups have been prepared by a synthetic approach involving first introduction of a spacer between the piperidine and the functional group by reductive amination of piperidinone. The formation of each of these functional groups was carried out using N-N'-di(tert-butoxycarbonyl)thiourca and 2-methylthioimidazolinium iodide, respectively. These structures have been designed to incorporate two pharmacologic goals into one entity. Radioligand binding assays have been used to study their affinity for opioid (A, 5 and K) and 1(2)-imidazoline receptors. Two of them, 10 and 16, showed high affinity for mu opioid receptors and functionally they had moderate analgesic properties in the hot plate and writhing tests. The in vitro studies on guinea pig ileum (GPI) indicated that both compounds are mu opioid agonists. In what concerns 12-imidazoline receptor activity, these derivatives showed low affinity around 6 to 7 times less than idazoxan. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00356-x

文献信息

• Synthesis and pharmacological studies of new hybrid derivatives of fentanyl active at the μ-opioid receptor and I2–imidazoline binding sites
  作者：Christophe Dardonville、Cristina Fernandez-Fernandez、Sarah-Louise Gibbons、Gary J. Ryan、Nadine Jagerovic、Ane M. Gabilondo、J. Javier Meana、Luis F. Callado

  DOI：10.1016/j.bmc.2006.06.007

  日期：2006.10

  data (Ki mu=1.04+/-0.28 nM, Ki I2=409+/-238 nM), may possibly be due to the low intrinsic efficacy of the compound. Alternatively, a low access to the central nervous system for this kind of hybrid molecules cannot be ruled out. Two new compounds reported here (9f and 13), which were not dual acting, are worth mentioning for their outstanding binding affinities; 9f bound to the mu-opioid receptor with

  带有有效I2-咪唑啉结合位点（IBS）配体（即胍和BU224部分）的芬太尼衍生的两个杂化分子系列，与脂族（m = 2、3、4、6、7、8、9和12亚甲基）连接制备）或芳族间隔基。通过对人死后脑膜的竞争结合研究，确定它们对μ阿片受体和I2-IBS的亲和力。BU224杂合分子在微摩尔至低微摩尔范围内与μ阿片受体和I2-IBS结合，而链烷胍系列在这两个受体的纳摩尔范围内均表现出显着的亲和力。[35S] GTPgammaS功能测定是在人死后脑膜上进行的，每个系列的选定配体（4f和8g）均显示出对μ阿片受体和I2-IBS亲和力的最高双重亲和力。两种化合物都显示出激动剂特性：在链烷胍衍生物4f的mu阿片受体上（间隔：六个亚甲基单元）和在G蛋白偶联受体（GPCR）上仍需测定8g。缺乏体内4f的镇痛特性（即在小鼠中进行热板试验和扭体试验），与良好的体外结合数据（Ki mu = 1.04 +/- 0.28 nM，Ki