(2S)-2-amino-3-{[((3R)-1-{3-[1-(tert-butoxycarbonyl)-4-piperidinyl]propanoyl}-3-piperidinyl)carbonyl]amino}propanoic acid | 355388-24-8

• 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: (2S)-2-amino-3-{[((3R)-1-{3-[1-(tert-butoxycarbonyl)-4-piperidinyl]propanoyl}-3-piperidinyl)carbonyl]amino}propanoic acid
• 英文别名: N-[(R)-1-{3-(1-tertbutoxycarbonyl-4-piperidyl)propionyl}-3-piperidylcarbonyl]-2(S)-amino-beta-alanine；(2S)-2-amino-3-[[(3R)-1-[3-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]propanoyl]piperidine-3-carbonyl]amino]propanoic acid
• CAS: 355388-24-8
• 化学式: C₂₂H₃₈N₄O₆
• 分子量: 454.567
• InChiKey: BXCPPLVAWYGCME-SJORKVTESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -2.2
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  142
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S)-2-amino-3-{[((3R)-1-{3-[1-(tert-butoxycarbonyl)-4-piperidinyl]propanoyl}-3-piperidinyl)carbonyl]amino}propanoic acid 在 盐酸 作用下， 以 乙酸乙酯 为溶剂， 反应 2.0h， 以60%的产率得到(2S)-2-amino-3-[({(3R)-1-[3-(4-piperidinyl)propanoyl]-3-piperidinyl}carbonyl)amino]propanoic acid
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of potent GPIIb/IIIa antagonists: discovery of FK419

  摘要：

  The discovery of the non-peptide antiplatelet injectable agent FK419 is reported. Based on the P-turn structure of RGD peptide sequences in the a chain of fibrinogen, which binds the glycoprotein IIb/IIIa (GPIIb/IIIa) on the surface of platelets to induce platelet aggregation, the prototype 2 was designed. After further substituent effects were investigated at the a-position of the carboxylic acid in 2, we enhanced platelet aggregation inhibition, and discovered the useful feature of reduced prolongation of bleeding time. Finally, the potent platelet aggregation inhibitor FK419 (3) could be discovered. FK419 shows a safe feature of reduced prolongation of bleeding time, as well as potent inhibition of platelet aggregation. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.03.056
• 作为产物：
  描述：

  N-Boc-4-哌啶丙酸乙酯 在 palladium on activated charcoal lithium hydroxide 、 sodium hydroxide 、 氢气 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 (2S)-2-amino-3-{[((3R)-1-{3-[1-(tert-butoxycarbonyl)-4-piperidinyl]propanoyl}-3-piperidinyl)carbonyl]amino}propanoic acid
  参考文献：
  名称：

  Design, synthesis, and structure–activity relationships of potent GPIIb/IIIa antagonists: discovery of FK419

  摘要：

  The discovery of the non-peptide antiplatelet injectable agent FK419 is reported. Based on the P-turn structure of RGD peptide sequences in the a chain of fibrinogen, which binds the glycoprotein IIb/IIIa (GPIIb/IIIa) on the surface of platelets to induce platelet aggregation, the prototype 2 was designed. After further substituent effects were investigated at the a-position of the carboxylic acid in 2, we enhanced platelet aggregation inhibition, and discovered the useful feature of reduced prolongation of bleeding time. Finally, the potent platelet aggregation inhibitor FK419 (3) could be discovered. FK419 shows a safe feature of reduced prolongation of bleeding time, as well as potent inhibition of platelet aggregation. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.03.056

文献信息

• Beta-alanine derivatives and their use as receptor anatgonists
  申请人：——

  公开号：US20030018193A1

  公开（公告）日：2003-01-23

  A beta-alanine derivative of the formula (I) wherein R 1 is hydrogen atom or an amino protective group; A is a lower alkylene group or a lower alkenylene group; R 2 is hydrogen atom or an amino group which may be substituted with an acyl group; R 3 is hydrogen atom or an aryl or aralkyl group which may be substituted with one or more of hydroxy and/or lower alkoxy, a moiety represented by the formula (II), which is a bivalent N-containing 6- to 8-membered heterocyclic group, or a pharmaceutically acceptable salt thereof.

  公式（I）的β-丙氨酸衍生物，其中R1是氢原子或氨基保护基；A是较低的烷基或较低的烯基；R2是氢原子或氨基，可被酰基取代；R3是氢原子或芳基或芳基烷基，可被羟基和/或较低的烷氧基中的一个或多个取代的基团，该基团由公式（II）表示，是一种双价的含氮6-8元杂环基，或其药学上可接受的盐。
• Design, synthesis, and structure–activity relationships of potent GPIIb/IIIa antagonists: discovery of FK419
  作者：Toshio Yamanaka、Mitsuru Ohkubo、Satoru Kuroda、Hideko Nakamura、Fumie Takahashi、Toshiaki Aoki、Kayoko Mihara、Jiro Seki、Masayuki Kato

  DOI：10.1016/j.bmc.2005.03.056

  日期：2005.7

  The discovery of the non-peptide antiplatelet injectable agent FK419 is reported. Based on the P-turn structure of RGD peptide sequences in the a chain of fibrinogen, which binds the glycoprotein IIb/IIIa (GPIIb/IIIa) on the surface of platelets to induce platelet aggregation, the prototype 2 was designed. After further substituent effects were investigated at the a-position of the carboxylic acid in 2, we enhanced platelet aggregation inhibition, and discovered the useful feature of reduced prolongation of bleeding time. Finally, the potent platelet aggregation inhibitor FK419 (3) could be discovered. FK419 shows a safe feature of reduced prolongation of bleeding time, as well as potent inhibition of platelet aggregation. (c) 2005 Elsevier Ltd. All rights reserved.