Dmt-Sar-Phe-D-2-Nal-NH | 1018855-01-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: Dmt-Sar-Phe-D-2-Nal-NH
• 英文别名: (2S)-2-[[2-[[(2S)-2-amino-3-(4-hydroxy-2,6-dimethylphenyl)propanoyl]-methylamino]acetyl]amino]-N-[(2R)-1-amino-3-naphthalen-2-yl-1-oxopropan-2-yl]-3-phenylpropanamide
• CAS: 1018855-01-0
• 化学式: C₃₆H₄₁N₅O₅
• 分子量: 623.752
• InChiKey: LCSGBFCHAFMKLD-QAXCHELISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  168
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  Fmoc-L-苯丙氨酸 、 芴甲氧羰酰基肌氨酸 、 芴甲氧羰基-3-(2-萘)-D-丙氨酸 、 N-芴甲氧羰基-2,6-二甲基-L-酪氨酸 生成 Dmt-Sar-Phe-D-2-Nal-NH
  参考文献：
  名称：

  Novel highly potent μ-opioid receptor antagonist based on endomorphin-2 structure

  摘要：

  The mu-opioid agonists endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) exhibit an extremely high selectivity for the mu-opioid receptor and thus represent a potential framework for modi. cation into mu-antagonists. Here we report on the synthesis and biological evaluation of novel [D-2-Nal 4] endomorphin-2 analogs, [Sar(2), D-2-Nal(4)] endomorphin-2 and [Dmt(1), Sar(2), D-2-Nal(4)] endomorphin-2 (Dmt = 2'6'-dimethyltyrosine; Sar = N-methylglycine, sarcosine; D-2-Nal = 3-(2-naphthyl)- D- alanine). [Dmt(1), Sar(2), D-2-Nal(4)] endomorphin-2 possessed very high affinity for the mu-opioid receptor ( IC50 = 0.01 +/- 0.001 nM) and turned out to be a potent and extremely selective mu-opioid receptor antagonist, as judged by the in vitro aequorin luminescence-based calcium assay (pA(2) = 9.19). However, in the in vivo hot plate test in mice this analog was less potent than our earlier mu-opioid receptor antagonist, [Dmt(1), D-2-Nal(4)] endomorphin- 2 (antanal-2). The exceptional mu-opioid receptor in vitro activity and selectivity of [Dmt(1), Sar(2), D-2-Nal(4)] endomorphin- 2 makes this analog a valuable pharmacological tool, but further modi. cations are needed to improve its in vivo pro. le. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.009

文献信息

• Novel highly potent μ-opioid receptor antagonist based on endomorphin-2 structure
  作者：Jakub Fichna、Jean-Claude do-Rego、Tomasz Janecki、Renata Staniszewska、Jeroen Poels、Jozef Vanden Broeck、Jean Costentin、Peter W. Schiller、Anna Janecka

  DOI：10.1016/j.bmcl.2008.01.009

  日期：2008.2

  The mu-opioid agonists endomorphin-1 (Tyr-Pro-Trp-Phe-NH2) and endomorphin-2 (Tyr-Pro-Phe-Phe-NH2) exhibit an extremely high selectivity for the mu-opioid receptor and thus represent a potential framework for modi. cation into mu-antagonists. Here we report on the synthesis and biological evaluation of novel [D-2-Nal 4] endomorphin-2 analogs, [Sar(2), D-2-Nal(4)] endomorphin-2 and [Dmt(1), Sar(2), D-2-Nal(4)] endomorphin-2 (Dmt = 2'6'-dimethyltyrosine; Sar = N-methylglycine, sarcosine; D-2-Nal = 3-(2-naphthyl)- D- alanine). [Dmt(1), Sar(2), D-2-Nal(4)] endomorphin-2 possessed very high affinity for the mu-opioid receptor ( IC50 = 0.01 +/- 0.001 nM) and turned out to be a potent and extremely selective mu-opioid receptor antagonist, as judged by the in vitro aequorin luminescence-based calcium assay (pA(2) = 9.19). However, in the in vivo hot plate test in mice this analog was less potent than our earlier mu-opioid receptor antagonist, [Dmt(1), D-2-Nal(4)] endomorphin- 2 (antanal-2). The exceptional mu-opioid receptor in vitro activity and selectivity of [Dmt(1), Sar(2), D-2-Nal(4)] endomorphin- 2 makes this analog a valuable pharmacological tool, but further modi. cations are needed to improve its in vivo pro. le. (c) 2008 Elsevier Ltd. All rights reserved.