(E)-ethyl 4-(2-(ethylthio)benzylideneamino)butanoate | 900175-31-7

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: (E)-ethyl 4-(2-(ethylthio)benzylideneamino)butanoate
• CAS: 900175-31-7
• 化学式: C₁₅H₂₁NO₂S
• 分子量: 279.403
• InChiKey: PRYBRFCURHZOPI-FOWTUZBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.56
• 重原子数：
  19.0
• 可旋转键数：
  8.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  38.66
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (E)-ethyl 4-(2-(ethylthio)benzylideneamino)butanoate 在 盐酸 、 oxone 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 11.0h， 生成 (2R,3S)-ethyl 2-(2-(ethylsulfonyl)phenyl)pyrrolidine-3-carboxylate
  参考文献：
  名称：

  Design and Synthesis of Phenylpyrrolidine Phenylglycinamides As Highly Potent and Selective TF-FVIIa Inhibitors

  摘要：

  Inhibitors of the Tissue Factor/Factor VIIa (TF-FVIIa) complex are promising novel anticoagulants that show excellent efficacy and minimal bleeding in preclinical models. On the basis of a zwitterionic phenylglycine acylsulfonamide 1, a phenylglycine benzylamide 2 was shown to possess improved permeability and oral bioavailability. Optimization of the benzylamide, guided by X-ray crystallography, led to a potent TF-FVIIa inhibitor 18i with promising oral bioavailability, but promiscuous activity in an in vitro safety panel of receptors and enzymes. Introducing an acid on the pyrrolidine ring, guided by molecular modeling, resulted in highly potent, selective, and efficacious TF-FVIIa inhibitors with clean in vitro safety profile. The pyrrolidine acid 20 showed a moderate clearance, low volume of distribution, and a short t(1/2) in dog PK studies.

  DOI：

  10.1021/ml400453z
• 作为产物：
  描述：

  2-(乙硫基)苯(甲)醛 、 4-氨基丁酸乙酯.盐酸盐 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (E)-ethyl 4-(2-(ethylthio)benzylideneamino)butanoate
  参考文献：
  名称：

  Design and Synthesis of Phenylpyrrolidine Phenylglycinamides As Highly Potent and Selective TF-FVIIa Inhibitors

  摘要：

  Inhibitors of the Tissue Factor/Factor VIIa (TF-FVIIa) complex are promising novel anticoagulants that show excellent efficacy and minimal bleeding in preclinical models. On the basis of a zwitterionic phenylglycine acylsulfonamide 1, a phenylglycine benzylamide 2 was shown to possess improved permeability and oral bioavailability. Optimization of the benzylamide, guided by X-ray crystallography, led to a potent TF-FVIIa inhibitor 18i with promising oral bioavailability, but promiscuous activity in an in vitro safety panel of receptors and enzymes. Introducing an acid on the pyrrolidine ring, guided by molecular modeling, resulted in highly potent, selective, and efficacious TF-FVIIa inhibitors with clean in vitro safety profile. The pyrrolidine acid 20 showed a moderate clearance, low volume of distribution, and a short t(1/2) in dog PK studies.

  DOI：

  10.1021/ml400453z

文献信息

• PHENYLGLYCINAMIDE DERIVATIVES USEFUL AS ANTICOAGULANTS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1856096B1

  公开（公告）日：2010-09-01
• US7622585B2
  申请人：——

  公开号：US7622585B2

  公开（公告）日：2009-11-24
• [EN] PHENYLGLYCINAMIDE DERIVATIVES USEFUL AS ANTICOAGULANTS<br/>[FR] DERIVES DE PHENYLGLYCINAMIDE UTILISES COMME ANTICOAGULANTS
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2006076246A2

  公开（公告）日：2006-07-20

  [EN] The present invention relates generally to phenylglycinamide derivatives that inhibit serine proteases. In particular it is directed to novel phenylglycinamide derivatives, and analogues thereof, which are useful as selective inhibitors of serine protease enzymes of the coagulation cascade; for example thrombin, factor VIIa, factor Xa, factor XIa, factor IXa, and/or plasma kallikrein. In particular, it relates to compounds that are factor VIIa inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of using the same.
  [FR] La présente invention concerne de manière générale des dérivés de phénylglycinamide inhibant les sérines protéases. L'invention concerne en particulier de nouveaux dérivés de phénylglycinamide, et des analogues de ceux-ci, utilisés comme inibiteurs sélectifs des sérines protéases de la cascade de coagulation, par exemple la thrombine, le facteur VIIa, le facteur Xa, le facteur XIa, le facteur IXa, et/ou la kallikréine plasmatique. L'invention concerne en particulier des composés inhibiteurs du facteur VIIa. L'invention concerne également des compositions pharmaceutiques contenant lesdits composés, et des méthodes d'utilisation de ceux-ci.