(3S,6R,9S,12R)-3,9-dibenzyl-6-methyl-1,4,7,10-tetrazabicyclo[10.3.0]pentadecane-2,5,8,11-tetrone | 1176206-43-1

• 英文名称: (3S,6R,9S,12R)-3,9-dibenzyl-6-methyl-1,4,7,10-tetrazabicyclo[10.3.0]pentadecane-2,5,8,11-tetrone
• CAS: 1176206-43-1
• 化学式: C₂₆H₃₀N₄O₄
• 分子量: 462.549
• InChiKey: LTBLKAZGCWAXOX-KDXIVRHGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  108
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  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， 生成 (3S,6R,9S,12R)-3,9-dibenzyl-6-methyl-1,4,7,10-tetrazabicyclo[10.3.0]pentadecane-2,5,8,11-tetrone
  参考文献：
  名称：

  Alanine analogues of [D-Trp]CJ-15,208: novel opioid activity profiles and prevention of drug- and stress-induced reinstatement of cocaine-seeking behaviour

  摘要：

  Background and PurposeThe novel macrocyclic peptide cyclo[Phe‐D‐Pro‐Phe‐D‐Trp] ([D‐Trp]CJ‐15,208) exhibits κ opioid (KOP) receptor antagonist activity in both in vitro and in vivo assays. The four alanine analogues of this peptide were synthesized and characterized both in vitro and in vivo to assess the contribution of different amino acid residues to the activity of [D‐Trp]CJ‐15,208.Experimental ApproachThe peptides were synthesized by a combination of solid phase peptide synthesis and cyclization in solution. The analogues were evaluated in vitro in receptor binding and functional assays, and in vivo with mice using a tail‐withdrawal assay for antinociceptive and opioid antagonist activity. Mice demonstrating extinction of cocaine conditioned‐place preference (CPP) were pretreated with selected analogues to evaluate prevention of stress or cocaine‐induced reinstatement of CPP.Key ResultsThe alanine analogues displayed pharmacological profiles in vivo distinctly different from [D‐Trp]CJ‐15,208. While the analogues exhibited varying opioid receptor affinities and κ and μ opioid receptor antagonist activity in vitro, they produced potent opioid receptor‐mediated antinociception (ED50 = 0.28–4.19 nmol, i.c.v.) in vivo. Three of the analogues also displayed KOP receptor antagonist activity in vivo. Pretreatment with an analogue exhibiting both KOP receptor agonist and antagonist activity in vivo prevented both cocaine‐ and stress‐induced reinstatement of cocaine‐seeking behaviour in the CPP assay in a time‐dependent manner.Conclusions and ImplicationsThese unusual macrocyclic peptides exhibit in vivo opioid activity profiles different from the parent compound and represent novel compounds for potential development as therapeutics for drug abuse and possibly as analgesics.

  DOI：

  10.1111/bph.12664

文献信息

• 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.
• CYCLIC TETRAPEPTIDE ANALOGS
  申请人：University of Kansas

  公开号：US20210024576A1

  公开（公告）日：2021-01-28

  The present technology provides compounds of Formula I (or pharmaceutically acceptable salts and/or solvates thereof) that are useful in treating a CNS-related disorder such as schizophrenia, schizoaffective disorder, migraine, depression, pain, drug addiction, drug use, and/or drug seeking behavior. Also provided are compositions, medicaments, and methods including such compounds.
• US8809278B2
  申请人：——

  公开号：US8809278B2

  公开（公告）日：2014-08-19