methyl 1-[3-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenyl]pyrrolidine-3-carboxylate | 946397-79-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: methyl 1-[3-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenyl]pyrrolidine-3-carboxylate
• 英文别名: methyl 1-[3-[(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl]sulfonylphenyl]pyrrolidine-3-carboxylate
• CAS: 946397-79-1
• 化学式: C₂₄H₂₇F₄N₃O₄S
• 分子量: 529.556
• InChiKey: WIAOEHXPHMNOKO-TZHYSIJRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  78.5
• 氢给体数：
  0
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  methyl 1-[3-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenyl]pyrrolidine-3-carboxylate 在 sodium hydroxide 作用下， 以 水 为溶剂， 以89%的产率得到1-[3-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenyl]pyrrolidine-3-carboxylic acid
  参考文献：
  名称：

  Piperazine Sulfonamides as Potent, Selective, and Orally Available 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors with Efficacy in the Rat Cortisone-Induced Hyperinsulinemia Model

  摘要：

  11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) is the enzyme that converts cortisone to cortisol. Evidence suggests that selective inhibition of 11 beta-HSD1 could treat diabetes and metabolic syndrome. Presented herein are the synthesis, structure-activity relationship, and in vivo evaluation of piperazine sulfonamides as 11 beta HSD1 inhibitors. Through modification of our initial lead 5a, we have identified potent and selective 11 beta-HSD1 inhibitors such as 13q and 13u with good pharmacokinetic properties.

  DOI：

  10.1021/jm8004948
• 作为产物：
  描述：

  3-吡咯烷甲酸甲酯 、 (2R)-1-[(3-bromophenyl)sulfonyl]-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazine 在 tris-(dibenzylideneacetone)dipalladium(0) 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 sodium t-butanolate 作用下， 以 甲苯 为溶剂， 以20.5%的产率得到methyl 1-[3-({(2R)-4-[4-fluoro-2-(trifluoromethyl)phenyl]-2-methylpiperazin-1-yl}sulfonyl)phenyl]pyrrolidine-3-carboxylate
  参考文献：
  名称：

  Piperazine Sulfonamides as Potent, Selective, and Orally Available 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors with Efficacy in the Rat Cortisone-Induced Hyperinsulinemia Model

  摘要：

  11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) is the enzyme that converts cortisone to cortisol. Evidence suggests that selective inhibition of 11 beta-HSD1 could treat diabetes and metabolic syndrome. Presented herein are the synthesis, structure-activity relationship, and in vivo evaluation of piperazine sulfonamides as 11 beta HSD1 inhibitors. Through modification of our initial lead 5a, we have identified potent and selective 11 beta-HSD1 inhibitors such as 13q and 13u with good pharmacokinetic properties.

  DOI：

  10.1021/jm8004948

文献信息

• 11-Beta HSD 1 inhibitors
  申请人：Xiang Shaoyun Jason

  公开号：US20070219198A1

  公开（公告）日：2007-09-20

  This invention relates to inhibiting 11βHSD1.

  该发明涉及抑制11βHSD1。
• 11-Beta HSD1 Inhibitors
  申请人：Xiang Jason Shaoyun

  公开号：US20100029648A1

  公开（公告）日：2010-02-04

  This invention relates to inhibiting 11βHSD1.

  本发明涉及抑制11βHSD1。
• US7632838B2
  申请人：——

  公开号：US7632838B2

  公开（公告）日：2009-12-15
• Piperazine Sulfonamides as Potent, Selective, and Orally Available 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors with Efficacy in the Rat Cortisone-Induced Hyperinsulinemia Model
  作者：Jason Xiang、Zhao-Kui Wan、Huan-Qiu Li、Manus Ipek、Eva Binnun、Jill Nunez、Lihren Chen、John C. McKew、Tarek S. Mansour、Xin Xu、Vipin Suri、May Tam、Yuzhe Xing、Xiangping Li、Seung Hahm、James Tobin、Eddine Saiah

  DOI：10.1021/jm8004948

  日期：2008.7.1

  11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) is the enzyme that converts cortisone to cortisol. Evidence suggests that selective inhibition of 11 beta-HSD1 could treat diabetes and metabolic syndrome. Presented herein are the synthesis, structure-activity relationship, and in vivo evaluation of piperazine sulfonamides as 11 beta HSD1 inhibitors. Through modification of our initial lead 5a, we have identified potent and selective 11 beta-HSD1 inhibitors such as 13q and 13u with good pharmacokinetic properties.