N-[(R)-1-{3-(1-tert-butoxycarbonyl-4-piperidyl)-propionyl}-3-piperidylcarbonyl]-β-alanine ethyl ester | 169495-73-2

• 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-[(R)-1-{3-(1-tert-butoxycarbonyl-4-piperidyl)-propionyl}-3-piperidylcarbonyl]-β-alanine ethyl ester
• 英文别名: tert-butyl 4-[3-[(3R)-3-[(3-ethoxy-3-oxopropyl)carbamoyl]piperidin-1-yl]-3-oxopropyl]piperidine-1-carboxylate
• CAS: 169495-73-2
• 化学式: C₂₄H₄₁N₃O₆
• 分子量: 467.606
• InChiKey: MWMGRZKLOABSHT-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-[(R)-1-{3-(1-tert-butoxycarbonyl-4-piperidyl)-propionyl}-3-piperidylcarbonyl]-β-alanine ethyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 生成 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 N-[(R)-1-{3-(1-tert-butoxycarbonyl-4-piperidyl)-propionyl}-3-piperidylcarbonyl]-β-alanine ethyl ester
  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 derivative and a process for the preparation thereof
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：US20010051730A1

  公开（公告）日：2001-12-13

  This invention relates to &bgr;-alanine derivatives represented by the following formula: 1 wherein each symbol is as defined in the specification and pharmaceutically acceptable salt thereof which is glycoprotein IIb/IIIa antagonist, inhibitor of blood platelets aggregation and inhibitor of the binding of fibrinogen to blood platelets, to processes for the preparation thereof, to a pharmaceutical composition comprising the same and to a method for the prevention and/or treatment diseases indicated in the specification to a human being or an animal.

  本发明涉及以下公式所表示的&bgr;-丙氨酸衍生物：1其中每个符号如说明书所定义的，并且其药学上可接受的盐是糖蛋白IIb/IIIa拮抗剂，血小板聚集抑制剂和纤维蛋白原与血小板结合的抑制剂，涉及其制备方法，包括它的制药组合物，以及用于预防和/或治疗说明书中所指示的人类或动物疾病的方法。
• N-(3-piperidinylcarbonyl)-beta-alanine derivatives as paf antagonists
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP1106606A2

  公开（公告）日：2001-06-13

  This invention relates to β-alanine derivatives represented by the following formula : wherein each symbol is as defined in the specification and pharmaceutically acceptable salt thereof which is glycoprotein IIb/IIIa antagonist, inhibitor of blood platelets aggregation and inhibitor of the binding of fibrinogen to blood platelets, to processes for the preparation thereof, to a pharmaceutical composition comprising the same and to a method for the prevention and/or treatment diseases indicated in the specification to a human being or an animal.

  本发明涉及由下式表示的 β-丙氨酸衍生物： 其中各符号如说明书中所定义，以及其药学上可接受的盐，它们是糖蛋白 IIb/IIIa 拮抗剂、血小板聚集抑制剂和纤维蛋白原与血小板结合抑制剂，还涉及其制备工艺、包含这些衍生物的药物组合物以及对人类或动物预防和/或治疗说明书中所述疾病的方法。
• N-(3-PIPERIDINYLCARBONYL)-BETA-ALANINE DERIVATIVES AS PAF ANTAGONISTS
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：EP0669912B1

  公开（公告）日：2001-12-05
• US6380215B1
  申请人：——

  公开号：US6380215B1

  公开（公告）日：2002-04-30
• [EN] N-(3-PIPERIDINYLCARBONYL)-BETA-ALANINE DERIVATIVES AS PAF ANTAGONISTS<br/>[FR] DERIVES DE N-(3-PIPERIDINYLCARBONYL)-BETA-ALANINE UTILISES COMME ANTAGONISTES DU FACTEUR D'AGREGATION PLAQUETTAIRE
  申请人：FUJISAWA PHARMACEUTICAL CO., LTD.

  公开号：WO1995008536A1

  公开（公告）日：1995-03-30

  (EN) This invention relates to $g(b)-alanine derivatives represented by formula (I), wherein each symbol is as defined in the specification and pharmaceutically acceptable salt thereof which is glycoprotein IIb/IIIa antagonist, inhibitor of blood platelets aggregation and inhibitor of the binding of fibrinogen to blood platelets, to processes for the preparation thereof, to a pharmaceutical composition comprising the same and to a method for the prevention and/or treatment of diseases indicated in the specification to a human being or an animal.(FR) L'invention se rapporte à des dérivés de $g(b)-alanine représentés par la formule (I), dans laquelle chaque symbole a la même notation que dans la description, et à un sel de ces dérivés acceptable en pharmacologie, qui est un antagoniste de la glycoprotéine IIb/IIIa, un inhibiteur de l'agrégation des plaquettes sanguines et un inhibiteur de la liaison du fibrinogène aux plaquettes sanguines. L'invention se rapporte également à des procédés de préparation de ce composé, à une composition pharmaceutique le contenant et à un procédé de prévention et/ou de traitement de maladies énumérées dans la description, chez l'homme ou l'animal.