Boc-Dmt-Pro-OH | 928232-30-8

• 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: Boc-Dmt-Pro-OH
• CAS: 928232-30-8
• 化学式: C₂₁H₃₀N₂O₆
• 分子量: 406.479
• InChiKey: VIUBETHXPPLURF-IRXDYDNUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.52
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  116.17
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  Boc-Dmt-Pro-OH 在 苯甲醚 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 2',6'-dimethyl-L-tyrosyl-L-prolyl-2'-ethyl-6'-methyl-L-phenylalanyl-L-phenylalanylamide
  参考文献：
  名称：

  Bifunctional [2‘,6‘-Dimethyl-l-tyrosine]endomorphin-2 Analogues Substituted at Position 3 with Alkylated Phenylalanine Derivatives Yield Potent Mixed μ-Agonist/δ-Antagonist and Dual μ-Agonist/δ-Agonist Opioid Ligands

  摘要：

  Endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2) and [Dmt(1)]EM-2 (Dmt = 2',6'-dimethyl-L-tyrosine) analogues, containing alkylated Phe(3) derivatives, 2'-monomethyl (2, 2'), 3',5'- and 2',6'-dimethyl (3, 3', and 4', respectively), 2',4',6'-trimethyl (6, 6'), 2'-ethyl-6'-methyl (7, 7'), and 2'-isopropyl-6'-methyl (8, 8') groups or Dmt (5, 5'), had the following characteristics: (i) [Xaa(3)]EM-2 analogues exhibited improved mu- and delta-opioid receptor affinities. The latter, however, were inconsequential (K-i(delta) = 491-3451 nM). (ii) [Dmt(1),Xaa(3)]EM-2 analogues enhanced mu- and delta-opioid receptor affinities (K-i(mu) = 0.069-0.32 nM; K-i(delta) = 1.83-99.8 nM) without kappa-opioid receptor interaction. (iii) There were elevated mu-bioactivity (IC50 = 0.12-14.4 nM) and abolished delta-agonism (IC50 > 10 mu M in 2', 3', 4', 5', 6'), although 4' and 6' demonstrated a potent mixed mu-agonism/delta-antagonism (for 4', IC50 mu = 0.12 and pA(2) = 8.15; for 6', IC50 mu = 0.21 nM and pA(2) = 9.05) and 7' was a dual mu-agonist/delta-agonist (IC50 mu = 0.17 nM; IC50 delta = 0.51 nM).

  DOI：

  10.1021/jm061238m
• 作为产物：
  描述：

  在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以98%的产率得到Boc-Dmt-Pro-OH
  参考文献：
  名称：

  Transformation of μ-opioid receptor agonists into biologically potent μ-opioid receptor antagonists

  摘要：

  N-Allylation (-CH2-CH=CH2) of [Dmt(1)]endomorphins yielded the following: (i) [N-allyl-Dmt(1)]endomorphin-2 (Dmt = 2',6'-dimethyl-L-tyrosine) (12) and [N-allyl-Dmt(1)]endomorphin-1 (15) (K-i mu = 0.45 and 0.26 nM, respectively) became p-antagonists (pA(2) = 8.59 and 8.18, respectively) with weak delta-antagonism (pA(2) = 6.32 and 7.32, respectively); (ii) intracerebroventricularly administered 12 inhibited morphine-induced CNS-mediated antinociception in mice [AD(50) (0.148 ng/mouse) was 16-fold more potent than naloxone], but not spinal antinociception, and (iii) 15 reversed the alcohol-elevated frequency in spontaneous inhibitory post-synaptic currents (IPSC) in hippocampal CA1 pyramidal cells in rat brain slices (P = 0.0055). Similarly, N-allylation of the potent mu-opioidmimetic agonists, 1,6-bis-[H-Dmt-NH]-hexane and 3,6-bis-[Dmt-NH-propyl]-2(1H)-pyrazinone, converted them into p-antagonists (pA(2) = 7.23 and 7.17 for the N-allyl-derivatives 17 and 19, respectively), and exhibited weak delta-antagonism. Thus, N-allylation of Dmt containing opioid peptides or opioidmimetics; continues to provide a facile means to convert selective mu-opioid agonists into potent mu-opioid antagonists. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.11.019

文献信息

• Endomorphin-1 analogs containing α-methyl-β-amino acids exhibit potent analgesic activity after peripheral administration
  作者：Yuan Wang、Junxian Yang、Xin Liu、Long Zhao、Dongxu Yang、Jingjing Zhou、Dan Wang、Lingyun Mou、Rui Wang

  DOI：10.1039/c7ob01115f

  日期：——

  This study describes the design and synthesis of endomorphin-1 analogs containing C-terminal aromatic α-methyl-β-amino acids and an N-terminal native tyrosine or 2,6-dimethyl-tyrosine. We show that, in comparison with the parent peptide, these analogs exhibit improved bioactivity and blood–brain barrier penetration after intravenous administration, and have a lower tendency to induce constipation and

  这项研究描述了含有C末端芳香族α-甲基-β-氨基酸和N末端天然酪氨酸或2,6-二甲基酪氨酸的内啡肽-1类似物的设计和合成。我们显示，与母体肽相比，这些类似物在静脉内给药后表现出更高的生物活性和血脑屏障渗透性，并且比吗啡具有更低的诱发便秘和镇静作用的趋势。