cyclo[Phe-D-Pro-Phe-Trp] | 210236-47-8

• 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: cyclo[Phe-D-Pro-Phe-Trp]
• 英文别名: c[L-Phe-D-pro-L-Phe-L-trp]；(3S,6S,9S,12R)-3,9-dibenzyl-6-(1H-indol-3-ylmethyl)-1,4,7,10-tetrazabicyclo[10.3.0]pentadecane-2,5,8,11-tetrone
• CAS: 210236-47-8
• 化学式: C₃₄H₃₅N₅O₄
• 分子量: 577.683
• InChiKey: GIZJWWQFOGQPRY-GCXHJFECSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  43
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  123
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  Trp-Phe-D-Pro-Phe 在 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以77%的产率得到cyclo[Phe-D-Pro-Phe-Trp]
  参考文献：
  名称：

  通用的撬锁，可访问所有阿片类药物受体：调节环肽肽c [Phe-d-Pro-Phe-Trp]（CJ-15,208）的选择性和功能谱

  摘要：

  近来，含色氨酸的不可阳离子化的阿片样肽肽以非典型结构出现并且具有意想不到的体内活性。本文中，我们描述了天然存在的混合κ/μ-配体c [Phe- d -Pro-Phe-Trp] 1（CJ-15,208）的类似物。受体亲和力，选择性和激动/拮抗作用随大环化合物尺寸的增加而变化，从而得到以低纳摩尔亲和力为特征的μ-激动剂9或δ-激动剂10。特别地，显示出在全身给药后，内脏痛的小鼠模型中，μ激动剂c [β-Ala- d -Pro-Phe-Trp] 9引起有效的抗伤害感受。

  DOI：

  10.1021/acs.jmedchem.6b00420

文献信息

• Cyclic tetrapeptide stereoisomers
  申请人：University of Kansas

  公开号：US10259843B2

  公开（公告）日：2019-04-16

  Cyclic tetrapeptide stereochemical isomers of CJ-15,208, pharmaceutical compositions from such cyclic tetrapeptides, and methods of using such pharmaceutical compositions. The cyclic tetrapeptide compounds and pharmaceutical compositions disclosed herein are potent analgesics active in several pain models with generally minimal tolerance and reduced likelihood to induce addiction relative to other known opiates.

  CJ-15,208的环状四肽立体化学异构体、这种环状四肽的药物组合物以及使用这种药物组合物的方法。本文公开的环四肽化合物和药物组合物是在多种疼痛模型中有效的强效镇痛剂，与其他已知的阿片类药物相比，其耐受性通常很小，诱发成瘾的可能性也较低。
• Synthesis of CJ-15,208, a novel κ-opioid receptor antagonist
  作者：Nicolette C. Ross、Santosh S. Kulkarni、Jay P. McLaughlin、Jane V. Aldrich

  DOI：10.1016/j.tetlet.2010.07.086

  日期：2010.9

  The tryptophan isomers of the cyclic tetrapeptide CJ-15,208, reported to be a kappa opioid receptor (KOR) antagonist [Saito, T.; Hirai, H.; Kim, Y. J.: Kojima, Y.; Matsunaga, Y.; Nishida, H.; Sakakibara, T.; Suga, O.; Sujaku, T.; Kojima, N. J. Antibiot. (Tokyo) 2002, 55, 847-854.], were synthesized to determine the tryptophan stereochemistry in the natural product. A strategy was developed to select linear precursor peptides that favor cyclization using molecular modeling, and optimized cyclization conditions are reported. The optical rotation of the L-Trp isomer is consistent with that of the natural product. Unexpectedly both isomers exhibit similar nanomolar affinity for KOR. (C) 2010 Elsevier Ltd. All rights reserved.
• The Macrocyclic Peptide Natural Product CJ-15,208 Is Orally Active and Prevents Reinstatement of Extinguished Cocaine-Seeking Behavior
  作者：Jane V. Aldrich、Sanjeewa N. Senadheera、Nicolette C. Ross、Michelle L. Ganno、Shainnel O. Eans、Jay P. McLaughlin

  DOI：10.1021/np300697k

  日期：2013.3.22

  The macrocyclic tetrapeptide natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]) exhibited both dose-dependent antinociception and kappa opioid receptor (KOR) antagonist activity after oral administration. CJ-15,208 antagonized a centrally administered KOR selective agonist, providing strong evidence it crosses the blood brain barrier to reach KOR in the CNS. Orally administered CJ-15,208 also prevented both cocaine- and stress-induced reinstatement of extinguished cocaine-seeking behavior in the conditioned place preference assay in a time- and dose-dependent manner. Thus, CJ-15,208 is a promising lead compound with a unique activity profile for potential development, particularly as a therapeutic to prevent relapse to drug-seeking behavior in abstinent subjects.
• CYCLIC TETRAPEPTIDE STEREOISOMERS
  申请人：The University of Kansas

  公开号：EP3166625B1

  公开（公告）日：2019-05-01
• CYCLIC TETRAPEPTIDES
  申请人：Aldrich Jane V.

  公开号：US20110190212A1

  公开（公告）日：2011-08-04

  Cyclic tetrapeptides that are kappa opioid receptor (KOR) antagonists can be used in therapeutic applications for treating, inhibiting, and/or preventing drug addiction, drug use, or drug seeking behavior in a subject. This can include subjects that have a history of drug addiction. The drug can be selected from cocaine, alcohol, amphetamines, methamphetamines, nicotine, opiate, or combinations thereof. These cyclic tetrapeptides can also be useful for treating, inhibiting, and/or preventing stress-induced drug seeking behavior.