(Nα-Bzl)(Nα-Me)Arg(Tos) | 74071-59-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (Nα-Bzl)(Nα-Me)Arg(Tos)
• 英文别名: Bzl-MeArg(Tos)-OH；(N^α-Bzl)(N^α-Me)Arg(Tos)；H-(N-Bzl,N-Me)Arg(Tos)-OH
• CAS: 74071-59-3
• 化学式: C₂₁H₂₈N₄O₄S
• 分子量: 432.544
• InChiKey: XUXGICKUHCMFJR-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.16
• 重原子数：
  30.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  122.59
• 氢给体数：
  4.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (Nα-Bzl)(Nα-Me)Arg(Tos) 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 溶剂黄146 为溶剂， 反应 6.0h， 以37%的产率得到H-MeArg(Tos)-OH
  参考文献：
  名称：

  Development of a small RGD peptide fibrinogen receptor antagonist with potent antiaggregatory activity in vitro

  摘要：

  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.

  DOI：

  10.1021/jm00114a022
• 作为产物：
  描述：

  苯甲醛 在 甲酸 、 sodium cyanoborohydride 作用下， 以 甲醇 、 水 为溶剂， 反应 18.17h， 生成 (Nα-Bzl)(Nα-Me)Arg(Tos)
  参考文献：
  名称：

  Development of a small RGD peptide fibrinogen receptor antagonist with potent antiaggregatory activity in vitro

  摘要：

  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.

  DOI：

  10.1021/jm00114a022

文献信息

• Ali; Bennett; Calvo, Journal of Medicinal Chemistry, 1994, vol. 37, # 6, p. 769 - 780
  作者：Ali、Bennett、Calvo、Elliott、Hwang、Ku、Lago、Nichols、Romoff、Shah、Vasko、Wong、Yellin、Yuan、Samanen

  DOI：——

  日期：——