H-Asp(OBzl)-NHCH2CH2C6H5*TFA | 108279-24-9

• 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-Asp(OBzl)-NHCH2CH2C6H5*TFA
• CAS: 108279-24-9
• 化学式: C₂HF₃O₂*C₁₉H₂₂N₂O₃
• 分子量: 440.419
• InChiKey: HTSPOLQDFRZLNG-LMOVPXPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.44
• 重原子数：
  31.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  118.72
• 氢给体数：
  3.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  Nε-Z-NAlpha-叔丁氧羰基-L-赖氨酸羟基琥珀酰亚胺酯 、 H-Asp(OBzl)-NHCH2CH2C6H5*TFA 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  Analogues of the Cholecystokinin C-Terminal Tetrapeptide

  摘要：

  从胆囊收缩素的羧基末端四肽部分合成了取代苯乙基酰胺和苯乙基酯Va - Vj，对它们的生物学性质进行了测定。在原始的CCK四肽结构Trp-Met-Asp-Phe-NH2中，Met被Lys(Pamc)取代，末端的Phe-NH2被Phe-NHCH2C6H5或Phe-OCH2C6H5取代，苯环中的取代程度不同。生物测定显示，这些简单的CCK类似物选择性地结合到胰腺的A受体，而在大脑中没有发现与B受体的结合。其中一些化合物表现为弱的CCK活性抑制剂，对胆囊和豚鼠回肠的收缩没有影响。

  DOI：

  10.1135/cccc19942511
• 作为产物：
  描述：

  Boc-L-天冬氨酸 4-苄酯 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 生成 H-Asp(OBzl)-NHCH2CH2C6H5*TFA
  参考文献：
  名称：

  Analogues of the Cholecystokinin C-Terminal Tetrapeptide

  摘要：

  从胆囊收缩素的羧基末端四肽部分合成了取代苯乙基酰胺和苯乙基酯Va - Vj，对它们的生物学性质进行了测定。在原始的CCK四肽结构Trp-Met-Asp-Phe-NH2中，Met被Lys(Pamc)取代，末端的Phe-NH2被Phe-NHCH2C6H5或Phe-OCH2C6H5取代，苯环中的取代程度不同。生物测定显示，这些简单的CCK类似物选择性地结合到胰腺的A受体，而在大脑中没有发现与B受体的结合。其中一些化合物表现为弱的CCK活性抑制剂，对胆囊和豚鼠回肠的收缩没有影响。

  DOI：

  10.1135/cccc19942511

文献信息

• Development of a small RGD peptide fibrinogen receptor antagonist with potent antiaggregatory activity in vitro
  作者：J. Samanen、F. Ali、T. Romoff、R. Calvo、E. Sorenson、J. Vasko、B. Storer、D. Berry、D. Bennett、M. Strohsacker、D. Powers、J. Stadel、A. Nichols

  DOI：10.1021/jm00114a022

  日期：1991.10.1

  The development of potent antithrombotic agents from the fibrinogen platelet receptor binding sequences Fg-alpha 572-575-Arg-Gly-Asp-Ser- and Fg-gamma 400-411-HHLGGAKQAGDV, believed to be a cryptic RGD-type sequence, is described. The tetrapeptide Ac-RGDS-NH2 itself is capable of inhibiting platelet aggregation in vitro at high concentrations, IC50 91.3 +/- 0.1-mu-M [in vitro antiaggregatory activity employing dog platelet rich plasma (PRP)/ADP], due to low platelet fibrinogen receptor affinity, K(i) 2.9 +/- 1.9-mu-M (purified, reconstituted human platelet GPIIb/IIIa), relative to fibrinogen, K(i) 38.0 +/- 6.0 nM. The peptide is also unstable to plasma, suffering total loss of in vitro activity upon incubation in PRP for 3 h (T1/2 90 min). Only modest improvements in potency were achieved with linear analogues of Ac-RGDS-NH2, while dramatic results were achieved with cyclic analogues, culminating in the cyclic disulfide Ac-cyclo-S,S-[Cys-(N-alpha-Me)Arg-Gly-Asp-Pen]-NH2 (SK&F 106760) with improved plasma stability (100% activity after 3 h), affinity (K(i) 58 +/- 20 nM purified human receptor), and potency (IC50 0.36 +/- 0.4-mu-M dog PRP/ADP). The affinity of this peptide is 2 orders of magnitude greater than that of Ac-RGDS-NH2. The affinity of the analogue is also comparable to fibrinogen. This peptide constitutes a first potent small peptide entry into the class of novel antithrombotic agents called fibrinogen receptor antagonists.
• Synthesis of gastrin antagonists, analogs of the C-terminal tetrapeptide of gastrin, by introduction of a .beta.-homo residue
  作者：M. Rodriguez、P. Fulcrand、J. Laur、A. Aumelas、J. P. Bali、Jean Martinez

  DOI：10.1021/jm00123a003

  日期：1989.3

  A series of analogues of Boc-Trp-Leu-Asp-Phe-NH2, a potent gastrin agonist, were synthesized by introducing a beta-homo residue in the sequence. These compounds were tested in vivo on acid secretion, in the anesthetized rat, and for their ability to inhibit binding of labeled gastrin to its receptors on gastric mucosal cells. These analogues behaved as gastrin antagonists. The most potent compounds in this series were Boc-Trp-Leu-beta-homo-Asp-NHCH2C6H5 (10) (IC50 = 1 microM, ED50 = 0.2 mg/kg), Boc-Trp-Leu-beta-homo-Asp-NHCH2CH2C6H5 (11) (IC50 = 0.75 microM, ED50 = 0.5 mg/kg), Boc-Trp-Leu-beta-homo-Asp-Phe-NH2 (12) (IC50 = 1.5 microM, ED50 = 0.1 mg/kg), and Boc-Trp-Leu-beta-homo-Asp-D-Phe-NH2 (13) (IC50 = 2 microM, ED50 = 0.1 mg/kg). We could demonstrate the importance of the region of the peptide bond between leucine and aspartic acid and of the structure of the C-terminal dipeptide Asp-Phe-NH2, for exhibiting biological activity on acid secretion.