ethyl (3R,4R)-4-[[2-fluoro-4-(2-oxopyridin-1-yl)phenyl]carbamoyl]pyrrolidine-3-carboxylate | 865528-40-1

• 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: ethyl (3R,4R)-4-[[2-fluoro-4-(2-oxopyridin-1-yl)phenyl]carbamoyl]pyrrolidine-3-carboxylate
• CAS: 865528-40-1
• 化学式: C₁₉H₂₀FN₃O₄
• 分子量: 373.384
• InChiKey: VNFRKRWFXDMOQX-KBPBESRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl (3R,4R)-4-[[2-fluoro-4-(2-oxopyridin-1-yl)phenyl]carbamoyl]pyrrolidine-3-carboxylate 、 2,2-二氟乙基三氟甲磺酸酯 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 以46%的产率得到ethyl (3R,4R)-1-(2,2-difluoroethyl)-4-[[2-fluoro-4-(2-oxopyridin-1-yl)phenyl]carbamoyl]pyrrolidine-3-carboxylate
  参考文献：
  名称：

  Discovery of a factor Xa inhibitor (3R,4R)-1-(2,2-difluoro-ethyl)-pyrrolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-amide} as a clinical candidate

  摘要：

  A series of (3R,4R)-pyrrolidine-3,4-dicarboxylic acid amides was investigated with respect to their factor Xa inhibitory activity, selectivity, pharmacokinetic properties, and ex vivo antithrombotic activity. The clinical candidate from this series, R1663, exhibits excellent selectivity against a panel of serine proteases and good pharmacokinetic properties in rats and monkeys. A Phase I clinical study with R1663 has been finalized.

  DOI：

  10.1016/j.bmcl.2010.06.126
• 作为产物：
  描述：

  (3R,4R)-4-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)phenylcarbamoyl]pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-ethyl ester 在 盐酸 作用下， 以 异丙醇 为溶剂， 反应 2.0h， 以100%的产率得到ethyl (3R,4R)-4-[[2-fluoro-4-(2-oxopyridin-1-yl)phenyl]carbamoyl]pyrrolidine-3-carboxylate
  参考文献：
  名称：

  Discovery of a factor Xa inhibitor (3R,4R)-1-(2,2-difluoro-ethyl)-pyrrolidine-3,4-dicarboxylic acid 3-[(5-chloro-pyridin-2-yl)-amide] 4-{[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenyl]-amide} as a clinical candidate

  摘要：

  A series of (3R,4R)-pyrrolidine-3,4-dicarboxylic acid amides was investigated with respect to their factor Xa inhibitory activity, selectivity, pharmacokinetic properties, and ex vivo antithrombotic activity. The clinical candidate from this series, R1663, exhibits excellent selectivity against a panel of serine proteases and good pharmacokinetic properties in rats and monkeys. A Phase I clinical study with R1663 has been finalized.

  DOI：

  10.1016/j.bmcl.2010.06.126

文献信息

• Cyclic amines
  申请人：Zbinden Groebke Katrin

  公开号：US20060247238A1

  公开（公告）日：2006-11-02

  The invention is concerned with cyclic amines of formula (I) wherein X 1 to X 3 , Y 1 to Y 3 , R 1′ , R 1″ and n are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit coagulation factor Xa and can be used as medicaments and for treating diseases associated with coagulation factor Xa.

  这项发明涉及公式(I)中的环氨基化合物，其中X1至X3，Y1至Y3，R1'，R1"和n如描述和索赔中定义的那样，以及其生理上可接受的盐。这些化合物抑制凝血因子Xa，并可用作药物治疗与凝血因子Xa相关的疾病。
• PROCESSES FOR THE MANUFACTURE OF A PYRROLIDINE-3,4-DICARBOXAMIDE DERIVATIVE
  申请人：Adam Jean-Michel

  公开号：US20080214826A1

  公开（公告）日：2008-09-04

  The invention is concerned with processes for the manufacture of the pyrrolidine-3,4-dicarboxamide derivative of formula (I), and the intermediates useful for those processes of manufacture.

  该发明涉及制造式(I)的吡咯烷-3,4-二羧酰胺衍生物的工艺，以及用于这些制造工艺的中间体。
• WO2008/77797
  申请人：——

  公开号：——

  公开（公告）日：——
• US7872141B2
  申请人：——

  公开号：US7872141B2

  公开（公告）日：2011-01-18
• US7820699B2
  申请人：——

  公开号：US7820699B2

  公开（公告）日：2010-10-26