(3S)-3-[(3-chloro-4-cyanophenyl)amino]-1-pyrrolidinecarboxylic acid methyl ester | 1034856-41-1

• 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: (3S)-3-[(3-chloro-4-cyanophenyl)amino]-1-pyrrolidinecarboxylic acid methyl ester
• 英文别名: methyl (3S)-3-(3-chloro-4-cyanoanilino)pyrrolidine-1-carboxylate
• CAS: 1034856-41-1
• 化学式: C₁₃H₁₄ClN₃O₂
• 分子量: 279.726
• InChiKey: WVKMVAKTUNHXKN-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (3S)-3-[(3-chloro-4-cyanophenyl)amino]-1-pyrrolidinecarboxylic acid methyl ester 、 2-氯苄溴 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 methyl (3S)-3-((3-chloro-4-cyanophenyl)[(2-chlorophenyl)methyl]amino)-1-pyrrolidinecarboxylate
  参考文献：
  名称：

  Improving the developability profile of pyrrolidine progesterone receptor partial agonists

  摘要：

  The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.092
• 作为产物：
  描述：

  2-chloro-4-[(3S)-3-pyrrolidinylamino]benzonitrile 、 氯甲酸甲酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以89%的产率得到(3S)-3-[(3-chloro-4-cyanophenyl)amino]-1-pyrrolidinecarboxylic acid methyl ester
  参考文献：
  名称：

  Improving the developability profile of pyrrolidine progesterone receptor partial agonists

  摘要：

  The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.10.092

文献信息

• Improving the developability profile of pyrrolidine progesterone receptor partial agonists
  作者：Lara S. Kallander、David G. Washburn、Tram H. Hoang、James S. Frazee、Patrick Stoy、Latisha Johnson、Qing Lu、Marlys Hammond、Linda S. Barton、Jaclyn R. Patterson、Leonard M. Azzarano、Rakesh Nagilla、Kevin P. Madauss、Shawn P. Williams、Eugene L. Stewart、Chaya Duraiswami、Eugene T. Grygielko、Xiaoping Xu、Nicholas J. Laping、Jeffrey D. Bray、Scott K. Thompson

  DOI：10.1016/j.bmcl.2009.10.092

  日期：2010.1

  The previously reported pyrrolidine class of progesterone receptor partial agonists demonstrated excellent potency but suffered from serious liabilities including hERG blockade and high volume of distribution in the rat. The basic pyrrolidine amine was intentionally converted to a sulfonamide, carbamate, or amide to address these liabilities. The evaluation of the degree of partial agonism for these non-basic pyrrolidine derivatives and demonstration of their efficacy in an in vivo model of endometriosis is disclosed herein. (C) 2009 Elsevier Ltd. All rights reserved.