N^α-Boc-D-Lys(Cbz)-(S)-(+)-Nip-OMe | 164224-44-6

• 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: N^α-Boc-D-Lys(Cbz)-(S)-(+)-Nip-OMe
• 英文别名: methyl (3S)-1-[(2R)-2-[(2-methylpropan-2-yl)oxycarbonylamino]-6-(phenylmethoxycarbonylamino)hexanoyl]piperidine-3-carboxylate
• CAS: 164224-44-6
• 化学式: C₂₆H₃₉N₃O₇
• 分子量: 505.612
• InChiKey: FIFUXRGCUUOEBU-LEWJYISDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  36
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N^α-Boc-D-Lys(Cbz)-(S)-(+)-Nip-OMe 在 palladium on activated charcoal N-甲基吗啉 、 lithium hydroxide 、 氢气 、 1-羟基苯并三唑 、 溶剂黄146 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 40.0h， 生成 N^α-Boc-D-Lys-(S)-(+)-Nip-β-Ala-OH diacetate
  参考文献：
  名称：

  Design and Evaluation of Nonpeptide Fibrinogen .gamma. Chain-Based GPIIB/IIIA Antagonists

  摘要：

  Two series of nonpeptide turn mimetics were designed by analysis of the solution NMR structure of the 385-411 sequence of the gamma-chain of fibrinogen. These compounds, based on the KQAGD (Lys-Gln-Ala-Gly-Asp, 406-410) sequence, were synthesized and studied in vitro. The most interesting compound from our study, RWJ 50042 (25), exhibits potent inhibition of fibrinogen binding to GPIIb/IIIa (IC50 = 0.009 mu M), as well as thrombin- or collagen-induced platelet aggregation (IC50 = 0.76, 0.14 mu M). Since the 400-411 sequence is required for gamma-chain bioactivity and is a unique recognition sequence among ligands for integrins, vis-a-vis other RGD (Arg-Gly-Asp)-presenting proteins, these turn mimetics may represent a new, selective approach to antagonism of the fibrinogen receptor.

  DOI：

  10.1021/jm00010a002
• 作为产物：
  描述：

  N2-[叔丁氧羰基]-N6-[苄氧羰基]-D-赖氨酸 、 (S)-3-哌啶甲酸甲酯盐酸盐 在 N-甲基吗啉 、 双(2-氧代-3-恶唑烷基)次磷酰氯 作用下， 生成 N^α-Boc-D-Lys(Cbz)-(S)-(+)-Nip-OMe
  参考文献：
  名称：

  Design and Evaluation of Nonpeptide Fibrinogen .gamma. Chain-Based GPIIB/IIIA Antagonists

  摘要：

  Two series of nonpeptide turn mimetics were designed by analysis of the solution NMR structure of the 385-411 sequence of the gamma-chain of fibrinogen. These compounds, based on the KQAGD (Lys-Gln-Ala-Gly-Asp, 406-410) sequence, were synthesized and studied in vitro. The most interesting compound from our study, RWJ 50042 (25), exhibits potent inhibition of fibrinogen binding to GPIIb/IIIa (IC50 = 0.009 mu M), as well as thrombin- or collagen-induced platelet aggregation (IC50 = 0.76, 0.14 mu M). Since the 400-411 sequence is required for gamma-chain bioactivity and is a unique recognition sequence among ligands for integrins, vis-a-vis other RGD (Arg-Gly-Asp)-presenting proteins, these turn mimetics may represent a new, selective approach to antagonism of the fibrinogen receptor.

  DOI：

  10.1021/jm00010a002

文献信息

• Design and Evaluation of Nonpeptide Fibrinogen .gamma. Chain-Based GPIIB/IIIA Antagonists
  作者：William J. Hoekstra、Mary Pat Beavers、Patricia Andrade-Gordon、Mary F. Evangelisto、Patricia M. Keane、Jeffery B. Press、Karen A. Tomko、Francis Fan、Marek Kloczewiak

  DOI：10.1021/jm00010a002

  日期：1995.5

  Two series of nonpeptide turn mimetics were designed by analysis of the solution NMR structure of the 385-411 sequence of the gamma-chain of fibrinogen. These compounds, based on the KQAGD (Lys-Gln-Ala-Gly-Asp, 406-410) sequence, were synthesized and studied in vitro. The most interesting compound from our study, RWJ 50042 (25), exhibits potent inhibition of fibrinogen binding to GPIIb/IIIa (IC50 = 0.009 mu M), as well as thrombin- or collagen-induced platelet aggregation (IC50 = 0.76, 0.14 mu M). Since the 400-411 sequence is required for gamma-chain bioactivity and is a unique recognition sequence among ligands for integrins, vis-a-vis other RGD (Arg-Gly-Asp)-presenting proteins, these turn mimetics may represent a new, selective approach to antagonism of the fibrinogen receptor.