(3R,4R)-3-(4-Chloro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-pyrrolidine | 865528-39-8

• 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: (3R,4R)-3-(4-Chloro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-pyrrolidine
• 英文别名: (3R,4R)-N3-(4-chlorophenyl)-N4-(2-fluoro-4-(2-oxopyridin-1(2H)-yl)phenyl)pyrrolidine-3,4-dicarboxamide；(3R,4R)-4-N-(4-chlorophenyl)-3-N-[2-fluoro-4-(2-oxopyridin-1-yl)phenyl]pyrrolidine-3,4-dicarboxamide
• CAS: 865528-39-8
• 化学式: C₂₃H₂₀ClFN₄O₃
• 分子量: 454.888
• InChiKey: NLAXOSJXKLHHCS-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  90.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3R,4R)-3-(4-Chloro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-pyrrolidine 、 氯甲酸丙酯 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 18.0h， 生成 (3R,4R)-3-(4-chlorophenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)phenylcarbamoyl]pyrrolidine-1-carboxylic acid propyl ester
  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-(4-chlorophenylcarbamoyl)pyrrolidine-1,3-dicarboxylic acid 1-tert-butyl ester 、 1-(4-氨基-3-氟苯基)吡啶-2(1h)-酮 在 氯化亚砜 作用下， 反应 18.0h， 以99%的产率得到(3R,4R)-3-(4-Chloro-phenylcarbamoyl)-4-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-pyrrolidine
  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

• [EN] NOVEL PYRROLIDINE-3,4-DICARBOXAMIDE DERIVATIVES<br/>[FR] NOUVEAUX DERIVES DE PYRROLIDINE-3,4-DICARBOXAMIDE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2005092881A1

  公开（公告）日：2005-10-06

  The invention is concerned with novel pyrrolidine-3,4-dicarboxamide derivatives of Formula (I) ; wherein Rl to R9 and X are as defined in the description and in the claims, as well as physiologically acceptable salts thereof. These compounds inhibit the coagulation factor Xa and can be used as medicaments.

  这项发明涉及一种新型的 Formula (I) 中的吡咯烷-3,4-二羧酰胺衍生物；其中 R1 到 R9 和 X 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，可用作药物。
• NOVEL PYRROLIDINE-3,4-DICARBOXAMIDE DERIVATIVES
  申请人：F. HOFFMANN-LA ROCHE AG

  公开号：EP1732918A1

  公开（公告）日：2006-12-20
• US7550487B2
  申请人：——

  公开号：US7550487B2

  公开（公告）日：2009-06-23
• 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
  作者：Lilli Anselm、David W. Banner、Jörg Benz、Katrin Groebke Zbinden、Jacques Himber、Hans Hilpert、Walter Huber、Bernd Kuhn、Jean-Luc Mary、Michael B. Otteneder、Narendra Panday、Fabienne Ricklin、Martin Stahl、Stefan Thomi、Wolfgang Haap

  DOI：10.1016/j.bmcl.2010.06.126

  日期：2010.9

  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.