tert-butyl 4-[3-((3R)-3-{[((2S)-2-{[(benzyloxy)carbonyl]amino}-3-methoxy-3-oxopropyl)amino]carbonyl}-1-piperidinyl)-3-oxopropyl]-1-piperidinecarboxylate | 223697-44-7

• 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: tert-butyl 4-[3-((3R)-3-{[((2S)-2-{[(benzyloxy)carbonyl]amino}-3-methoxy-3-oxopropyl)amino]carbonyl}-1-piperidinyl)-3-oxopropyl]-1-piperidinecarboxylate
• 英文别名: N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)propionyl]-3-piperidylcarbonyl]-2(S)-benzyloxycarbonylamino-beta-alanine methyl ester；tert-butyl 4-[3-[(3R)-3-[[(2S)-3-methoxy-3-oxo-2-(phenylmethoxycarbonylamino)propyl]carbamoyl]piperidin-1-yl]-3-oxopropyl]piperidine-1-carboxylate
• CAS: 223697-44-7
• 化学式: C₃₁H₄₆N₄O₈
• 分子量: 602.728
• InChiKey: SIELMDYHGAIUNL-RPBOFIJWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  43
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  144
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[3-((3R)-3-{[((2S)-2-{[(benzyloxy)carbonyl]amino}-3-methoxy-3-oxopropyl)amino]carbonyl}-1-piperidinyl)-3-oxopropyl]-1-piperidinecarboxylate 在 palladium on activated charcoal 盐酸 、 lithium hydroxide 、 氢气 作用下， 以 四氢呋喃 、 甲醇 、 乙酸乙酯 为溶剂， 反应 5.5h， 生成 (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 lithium hydroxide 、 sodium hydroxide 、 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 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 tert-butyl 4-[3-((3R)-3-{[((2S)-2-{[(benzyloxy)carbonyl]amino}-3-methoxy-3-oxopropyl)amino]carbonyl}-1-piperidinyl)-3-oxopropyl]-1-piperidinecarboxylate
  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

• New processes for producing beta-alanine derivatives
  申请人：Fujisawa Pharmaceutical Co. Ltd.

  公开号：US20030114488A1

  公开（公告）日：2003-06-19

  The present invention relates to processes for the preparation of &bgr;-alanine derivative shown by following formula (I): 1 wherein R 1 is amino protective group, and R 2 is acyl group, or a salt thereof, which comprises, subjecting a compound of the formula (II): 2 wherein R 1 is the same as defined above, and R 3 is protected carboxy, or a salt, to elimination reaction of carboxy protective group, and then to acylation reaction of amino group.

  本发明涉及制备以下式(I)所示的β-丙氨酸衍生物的方法：其中R1是氨基保护基，R2是酰基，或其盐。该方法包括将式(II)的化合物：其中R1与上述定义相同，R3是保护羧基，或其盐，进行羧基保护基的消除反应，然后进行氨基基的酰化反应。
• N-[(R)-1-[3-(4-piperidyl)propionyl]-3-piperidylcarbonyl]-2(S)-acetylamino-&bgr;-alanine trihydrate, compositions thereof, and methods for its use
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US06538007B1

  公开（公告）日：2003-03-25

  The trihydrates of &bgr;-alanine of the formula Are disclosed. Also method of antogonizing glycoprotein IIb/IIIa activity using these compounds is also disclosed.

  本文披露了公式为&bgr;-丙氨酸的三水合物。同时，本文还披露了使用这些化合物来拮抗糖蛋白IIb/IIIa活性的方法。
• 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.