Boc-Tyr-D-Ala-Gly-Phe-NH-NH2 | 66444-27-7

• 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-Tyr-D-Ala-Gly-Phe-NH-NH2
• 英文别名: Boc-Tyr-(D)-Ala-Gly-Phe-NHNH2；tert-butyl N-[(2S)-1-[[(2R)-1-[[2-[[(2S)-1-hydrazinyl-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]carbamate
• CAS: 66444-27-7
• 化学式: C₂₈H₃₈N₆O₇
• 分子量: 570.646
• InChiKey: KRYTVIYXIYKLGT-WTNAPCKOSA-N

物化性质

• 沸点：
  984.6±65.0 °C(Predicted)
• 密度：
  1.258±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  41
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  201
• 氢给体数：
  7
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Boc-Tyr-D-Ala-Gly-Phe-NH-NH2 在 钯 氢气 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 溶剂黄146 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (S)-2-Amino-N-{(R)-1-[({(S)-1-benzyl-2-[N'-((E)-but-2-enoyl)-hydrazino]-2-oxo-ethylcarbamoyl}-methyl)-carbamoyl]-ethyl}-3-(4-hydroxy-phenyl)-propionamide
  参考文献：
  名称：

  脑啡肽类似物的合成研究。I.H-Tyr-D-Ala-Gly-Phe-NHNH-CO-R（R ＝低级烷基）的有效止痛活性。

  摘要：

  合成了三十种脑啡肽的四肽酰肼类似物H-Tyr-D-Ala-Gly-Phe-NHN-(R1)-R2(R1, R2=H,烷基或酰基)。这些肽类经静脉或皮下注入小鼠后,测试其镇痛活性,并与吗啡进行比较,在合成的类似物中,四肽酰肼H-Tyr-D-Ala-Gly-Phe-NHNH-CO-R(R=低级烷基)活性最强,其镇痛活性比四肽酰胺H-Tyr-D-Ala-Gly-Phe-NH2强十倍,比吗啡弱一半。根据这些结果,讨论了新型脑啡肽类似物酰肼部分的构效关系。

  DOI：

  10.1248/cpb.29.3630
• 作为产物：
  描述：

  N-(tert-butyloxycarbonyl)-L-tyrosyl-D-alanine 在 N-羟基丁二酰亚胺 、 一水合肼 、 N,N'-二环己基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 Boc-Tyr-D-Ala-Gly-Phe-NH-NH2
  参考文献：
  名称：

  Hydrazone Linker as a Useful Tool for Preparing Chimeric Peptide/Nonpeptide Bifunctional Compounds

  摘要：

  The area of multitarget compounds, joining two pharmacophores within one molecule, is a vivid field of research in medicinal chemistry. Not only pharmacophoric elements are essential for the design and activity of such compounds, but the type and length of linkers used to connect them are also crucial. In the present contribution, we describe compound 1 in which a typical opioid peptide sequence is combined with a fragment characteristic for neurokinin-1 receptor (NKIR) antagonists through a hydrazone bridge. The compound has a high affinity for mu- and delta-opioid receptors (IC50=12.7 and 74.0 nM, respectively) and a weak affinity for the NK1R. Molecular modeling and structural considerations explain the observed activities. In in vivo test, intrathecal and intravenous administrations of 1 exhibited a strong analgesic effect, which indicates potential BBB penetration. This letter brings an exemplary application of the hydrazone linker for fast, facile, and successful preparation of chimeric compounds.

  DOI：

  10.1021/acsmedchemlett.6b00381

文献信息

• Antinociceptive and Cytotoxic Activity of Opioid Peptides with Hydrazone and Hydrazide Moieties at the C-Terminus
  作者：Jolanta Dyniewicz、Piotr F. J. Lipiński、Piotr Kosson、Marta Bochyńska-Czyż、Joanna Matalińska、Aleksandra Misicka

  DOI：10.3390/molecules25153429

  日期：——

  In the present contribution, we analyze the influence that C-terminal extension of short opioid peptide sequences by organic fragments has on receptor affinity, in vivo analgesic activity, and antimelanoma properties. The considered fragments were based on either N-acylhydrazone (NAH) or N′-acylhydrazide motifs combined with the 3,5-bis(trifluoromethyl)phenyl moiety. Eleven novel compounds were synthesized

  在目前的贡献中，我们分析了有机片段对短阿片肽序列的 C 端延伸对受体亲和力、体内镇痛活性和抗黑色素瘤特性的影响。所考虑的片段基于与 3,5-双（三氟甲基）苯基部分结合的 N-酰基腙（NAH）或 N'-酰基酰肼基序。合成了 11 种新化合物并进行了生物学评价。所分析的化合物对 µ 阿片受体 (MOR) 的亲和力范围广泛，对 δ 阿片受体 (DOR) 的亲和力相当低，并且没有明显的神经激肽-1 受体结合。在四对中的三对中，基于 N-酰腙的衍生物比它们的 N'-酰肼对应物更好地结合 MOR。最好的新型衍生物具有与参考阿片类药物（例如吗啡和双啡肽）相似的低纳摩尔 MOR 结合亲和力。将获得的 MOR 亲和力的顺序与分子对接的结果进行比较。在体内，四种测试化合物被证明是相对强的镇痛剂。最后，基于 NAH 的类似物减少了细胞培养中黑色素瘤细胞的数量，而它们的 N'-酰肼对应物则不会。抗黑色素瘤特性与化合物的亲脂性大致相关。而他们的
• Organic compounds
  申请人：Sandoz Ltd.

  公开号：US04247543A1

  公开（公告）日：1981-01-27

  The invention provides polypeptides of the formula, A-B-Gly-D-E-F wherein A is Tyr or substituted Tyr, B is, for example, -Gly-, -(D)-Ala-, or -(D)-Met-, D is Phe or substituted Phe, E is, for example, -Leu-, -Nle-, -Nva-, -Ile- or -Val-, and F is -NR.sub.7 CHR.sub.8 CH.sub.2 OR.sub.3 ', wherein, for example, R.sub.3 ' may be hydrogen or alkyl--CO--, R.sub.7 is hydrogen or alkyl and R.sub.8 is alkyl, which compounds possess pharmacological activity, for example, analgesic activity.

  本发明提供了多肽的公式A-B-Gly-D-E-F，其中A是酪氨酸或取代酪氨酸，B是例如-Gly-，-(D)-Ala-或-(D)-Met-，D是苯丙氨酸或取代苯丙氨酸，E是例如-Leu-，-Nle-，-Nva-，-Ile-或-Val-，F是-NR.sub.7 CHR.sub.8 CH.sub.2 OR.sub.3 '，其中，例如，R.sub.3'可以是氢或烷基--CO--，R.sub.7是氢或烷基，R.sub.8是烷基，这些化合物具有药理活性，例如镇痛活性。
• Filippi; Biondi; Filira, Farmaco, Edizione Scientifica, 1983, vol. 38, # 10, p. 713 - 724
  作者：Filippi、Biondi、Filira、Rocchi

  DOI：——

  日期：——
• Development of Novel Enkephalin Analogues that Have Enhanced Opioid Activities at Both μ and δ Opioid Receptors
  作者：Yeon Sun Lee、Ravil Petrov、Chad K. Park、Shou-wu Ma、Peg Davis、Josephine Lai、Frank Porreca、Ruben Vardanyan、Victor J. Hruby

  DOI：10.1021/jm061465o

  日期：2007.11.1

  Enkephalin analogues with a 4-anilidopiperidine scaffold have been designed and synthesized to achieve therapeutic benefit for the treatment of pain due to mixed mu and delta opioid agonist activities. Ligand 16, in which a Dmt-substituted enkephalin-like structure was linked to the N-phenyl-N-piperidin-4-yl propionamide moiety, showed very high binding affinities (0.4 nM) at mu and delta receptors with an increased hydrophobicity (aLogP = 2.96). This novel lead compound was found to have very potent agonist activities in MVD (1.8 nM) and GPI (8.5 nM) assays.
• Biological activity of fragments and analogues of the potent dimeric opioid peptide, biphalin
  作者：Andrzej W. Lipkowski、Aleksandra Misicka、Peg Davis、Dagmar Stropova、Jacqueline Janders、Magdalena Lachwa、Frank Porreca、Henry I. Yamamura、Victor J. Hruby

  DOI：10.1016/s0960-894x(99)00464-3

  日期：1999.9

  The synthesis and biological activity of two fragments of the very potent opioid peptide biphalin, showed that Tyr-D-Ala-Gly-Phe-NH-NH<-Phe is the minimal fragment necessary to express equal affinities and the same biological activity profile as the parent biphalin. The replacement of N'-Phe with other L or D- lipophilic amino acids showed the possibility of modification of receptor efficacy of the analogues. (C) 1999 Elsevier Science Ltd. All rights reserved.