(2R,3S)-ethyl 2-(2-(ethylsulfonyl)phenyl)pyrrolidine-3-carboxylate | 900175-36-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2R,3S)-ethyl 2-(2-(ethylsulfonyl)phenyl)pyrrolidine-3-carboxylate
• 英文别名: ethyl (2R,3S)-2-(2-ethylsulfonylphenyl)pyrrolidine-3-carboxylate
• CAS: 900175-36-2
• 化学式: C₁₅H₂₁NO₄S
• 分子量: 311.402
• InChiKey: LXTZUXIBQZQGNQ-JSGCOSHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  80.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2R,3S)-ethyl 2-(2-(ethylsulfonyl)phenyl)pyrrolidine-3-carboxylate 在 盐酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 水 、 乙酸乙酯 为溶剂， 反应 5.0h， 生成 (2R,3S)-1-((2R)-2-(1-aminoisoquinolin-6-ylamino)-2-(4-fluoro-3-methoxyphenyl)acetyl)-2-(2-(ethylsulfonyl)phenyl)pyrrolidine-3-carboxylic acid trifluoroacetic acid salt
  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 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

文献信息

• WO2006/76246
  申请人：——

  公开号：——

  公开（公告）日：——
• US7622585B2
  申请人：——

  公开号：US7622585B2

  公开（公告）日：2009-11-24