Boc-Tic-ε-Lys(Z)-OMe | 936835-77-7

• 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: Boc-Tic-ε-Lys(Z)-OMe
• CAS: 936835-77-7
• 化学式: C₃₀H₃₉N₃O₇
• 分子量: 553.656
• InChiKey: MOZWIQOTEJWEGR-DQEYMECFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  40.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  123.27
• 氢给体数：
  2.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  Boc-Tic-ε-Lys(Z)-OMe 在 N-甲基吗啉 、 sodium hydroxide 、 溶剂黄146 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.17h， 生成 tert-butyl (S)-3-(((S)-5-(1H-benzo[d]imidazol-2-yl)-5-(((benzyloxy)carbonyl)amino)pentyl)carbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate
  参考文献：
  名称：

  Further studies on the effect of lysine at the C-terminus of the Dmt-Tic opioid pharmacophore

  摘要：

  A wide range of activities are induced by Lys when introduced at C-terminus of the delta-opioid Dmt-Tic pharmacophore through the alpha-amine group, including: improved delta-antagonism, mu-agonism and p-antagonism. Here we report the synthesis of a new series of compounds with the general formula H-Dmt-Tic-NH-(CH2)(4)-CH(R)-R' (R = -NH2, -NH-Ac, -NH-Z; R'= CO-NH-Ph, -CO-NH-CH2-Ph, -Bid) in which Lys is linked to Dint-Tic through its side-chain amine group. All new compounds (1-9) displayed potent and selective delta-antagonism (MVD, pA(2) = 7.81-8.27), which was independent of the functionalized alpha-amine and carboxylic groups of C-terminal Lys. This behaviour suggests a direct application as a prototype intermediate, such as Boc-Dmt-Tic-epsilon-Lys(Z)OMe, which could be successfully applied in the synthesis (after Z or methyl ester removal) of unique designed multiple ligands containing the pharmacophore of the quintessential delta-antagonist Dmt-Tic and another opioid or biologically active non-opioid ligand. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.02.039
• 作为产物：
  描述：

  N-叔丁氧羰基-(S)-1,2,3,4-四氢异喹啉-3-羧酸 、 N-(benzyloxycarbonyl)lysine methyl ester hydrochloride 在 N-甲基吗啉 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 以78%的产率得到Boc-Tic-ε-Lys(Z)-OMe
  参考文献：
  名称：

  Further studies on the effect of lysine at the C-terminus of the Dmt-Tic opioid pharmacophore

  摘要：

  A wide range of activities are induced by Lys when introduced at C-terminus of the delta-opioid Dmt-Tic pharmacophore through the alpha-amine group, including: improved delta-antagonism, mu-agonism and p-antagonism. Here we report the synthesis of a new series of compounds with the general formula H-Dmt-Tic-NH-(CH2)(4)-CH(R)-R' (R = -NH2, -NH-Ac, -NH-Z; R'= CO-NH-Ph, -CO-NH-CH2-Ph, -Bid) in which Lys is linked to Dint-Tic through its side-chain amine group. All new compounds (1-9) displayed potent and selective delta-antagonism (MVD, pA(2) = 7.81-8.27), which was independent of the functionalized alpha-amine and carboxylic groups of C-terminal Lys. This behaviour suggests a direct application as a prototype intermediate, such as Boc-Dmt-Tic-epsilon-Lys(Z)OMe, which could be successfully applied in the synthesis (after Z or methyl ester removal) of unique designed multiple ligands containing the pharmacophore of the quintessential delta-antagonist Dmt-Tic and another opioid or biologically active non-opioid ligand. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.02.039

文献信息

• [EN] FLUORINE- SUBSTITUTED 2 ', 6 ' -DIMETHYL-L-TYROSINE-1, 2,3, 4-TETRAHYDR0IS0QUIN0LINE-3-CARB0XYLIC ACID PEPTIDES (DMT-TIC) FOR USE AS MYU- AND DELTA-OPIOID RECEPTOR PROBES IN<br/>[FR] COMPOSÉS DE DMT-TIC SUBSTITUÉS PAR DU FLUOR ET LEURS PROCÉDÉS D'UTILISATION
  申请人：US HEALTH

  公开号：WO2009032840A1

  公开（公告）日：2009-03-12

  Disclosed are compounds of formula (I) or pharmaceutically acceptable salts thereof: Formula (I) in which R1, R2, and R3 are described herein. Also disclosed is a pharmaceutical composition comprising at least one compound of formula (I) and a pharmaceutically acceptable carrier. Also disclosed is a method of locating a µ- and/or d-opioid receptor that is contained in a tissue or organ.

  揭示了化合物的结构式（I）或其药学上可接受的盐：结构式（I）中R1、R2和R3的描述如本文所述。还揭示了一种包含至少一种结构式（I）化合物和药学上可接受载体的药物组合物。还揭示了一种定位存在于组织或器官中的µ-和/或d-阿片受体的方法。
• Synthesis of a Potent and Selective ¹⁸F-Labeled δ-Opioid Receptor Antagonist Derived from the Dmt-Tic Pharmacophore for Positron Emission Tomography Imaging
  作者：Eun Kyoung Ryu、Zhanhong Wu、Kai Chen、Lawrence H. Lazarus、Ewa, D. Marczak、Yusuke Sasaki、Akihiro Ambo、Severo Salvadori、Chuancheng Ren、Heng Zhao、Gianfranco Balboni、Xiaoyuan Chen

  DOI：10.1021/jm7014765

  日期：2008.3.1

  Identification and pharmacological characterization of two new selective delta-opioid receptor antagonists, derived from the Dmt-Tic pharmacophore, of potential utility in positron emission tomography (PET) imaging are described. On the basis of its high delta selectivity, H-Dmt-Tic--Lys(Z)-OH (reference compound 1) is a useful starting point for the synthesis of (18)F-labeled compounds prepared by the

  描述了两种新的选择性 delta-阿片受体拮抗剂的鉴定和药理学表征，这些拮抗剂源自 Dmt-Tic 药效团，在正电子发射断层扫描 (PET) 成像中具有潜在的效用。基于其高 delta 选择性，H-Dmt-Tic--Lys(Z)-OH（参考化合物 1）是合成 (18)F 标记化合物的有用起点，该化合物通过 N-偶联制备。琥珀酰亚胺基 4-[ (18)F] 氟苯甲酸酯 ([(18)F]SFB) 与 Boc-Dmt-Tic--Lys(Z)-OH 在弱碱性条件下在 37°C 下反应 15 分钟，用 TFA 脱保护，和高效液相色谱纯化。总合成时间为 120 分钟，从 [(18)F]SFB (n = 5) 开始，[(18)F]-1 的衰减校正放射化学产率约为 25-30% ( n = 5)有效比活约为 46 GBq/微摩尔。体外放射自显影研究显示 [(18)F]-1 在纹状体和皮质中的显着吸收，并被