H-Tyr-D-Ala-Gly-Phe-NHNH2 | 72732-49-1

• 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: H-Tyr-D-Ala-Gly-Phe-NHNH2
• 英文别名: Tyr-D-Ala-Gly-Phe-NH-NH2；(S)-2-Amino-N-((R)-1-{[((S)-1-hydrazinocarbonyl-2-phenyl-ethylcarbamoyl)-methyl]-carbamoyl}-ethyl)-3-(4-hydroxy-phenyl)-propionamide；(2S)-2-amino-N-[(2R)-1-[[2-[[(2S)-1-hydrazinyl-1-oxo-3-phenylpropan-2-yl]amino]-2-oxoethyl]amino]-1-oxopropan-2-yl]-3-(4-hydroxyphenyl)propanamide
• CAS: 72732-49-1
• 化学式: C₂₃H₃₀N₆O₅
• 分子量: 470.528
• InChiKey: ASXZGPYHDUXBHW-CCKFTAQKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.8
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  189
• 氢给体数：
  7
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  Z-Tyr-D-Ala-Gly-Phe-NHNH2 在 钯 氢气 作用下， 以 甲醇 、 溶剂黄146 为溶剂， 生成 H-Tyr-D-Ala-Gly-Phe-NHNH2
  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

文献信息

• Tetrapeptidehydrazide derivatives
  申请人：Takeda Chemical Industries, Ltd

  公开号：US04277394A1

  公开（公告）日：1981-07-07

  Novel tetrapeptidehydrazide derivatives, inclusive of a pharmacologically acceptable acid addition salt thereof, which has the general formula (I): ##STR1## [wherein R.sub.1 is hydrogen or lower alkyl; R.sub.2 is hydrogen or the side chain of a D-.alpha.-amino acid; R.sub.3 is hydrogen or lower alkyl; R.sub.4 is hydrogen, or a saturated or unsaturated and straight or branched lower aliphatic acyl group which may optionally be substituted by hydroxy, amino, lower alkoxy, halogen, oxo, lower alkylthio or lower alkylthiooxide], are useful as analgesics.

  具有以下一般式（I）的新型四肽酸酐衍生物，包括其药学上可接受的酸盐： ##STR1## [其中R.sub.1是氢或低级烷基；R.sub.2是氢或D-.alpha.-氨基酸的侧链；R.sub.3是氢或低级烷基；R.sub.4是氢，或饱和或不饱和的直链或支链低级脂肪酰基，该基团可以选择性地被羟基，氨基，低级烷氧基，卤素，氧代，低级烷硫基或低级烷硫氧化物取代]，可用作镇痛剂。
• 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.
• Synthetic studies on enkephalin analogs. I. Potent analgesic activity of H-Tyr-D-Ala-Gly-Phe-NHNH-CO-R (R=lower alkyl).
  作者：SUSUMU SHINAGAWA、MASAHIKO FUJINO、HARUMITSU ISHII、KIYOHISA KAWAI

  DOI：10.1248/cpb.29.3630

  日期：——

  Thirty tetrapeptide hydrazide analogs of enkephalin, H-Tyr-D-Ala-Gly-Phe-NHN-(R1)-R2 (R1, R2=H, alkyl or acyl), were synthesized. The analgesic activities of these peptides were tested in mice after intravenous or subcutaneous injection, and compared with that of morphine. Among the analogs synthesized, the tetrapeptide acyl-hydrazide analog, H-Tyr-D-Ala-Gly-Phe-NHNH-CO-R (R=lower alkyl), was the most active and showed analgesic activity ten times more potent than that of the tetrapeptide amide analog, H-Tyr-D-Ala-Gly-Phe-NH2 and half as potent as that of morphine. On the basis of these results, structure-activity relations in the hydrazide part of enkephalin analogs of this new type are discussed.

  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。