N-[3-(5-{[(1S)-2-hydroxy-2-methyl-1-(methylcarbamoyl)propyl]carbamoyl}-2-furyl)benzyl]-2-(trifluoromethyl)pyrimidine-4-carboxamide | 1227192-35-9

• 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: N-[3-(5-{[(1S)-2-hydroxy-2-methyl-1-(methylcarbamoyl)propyl]carbamoyl}-2-furyl)benzyl]-2-(trifluoromethyl)pyrimidine-4-carboxamide
• 英文别名: (S)-N-(3-(5-(3-hydroxy-3-methyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)furan-2-yl)benzyl)-2-(trifluoromethyl)pyrimidine-4-carboxamide；N-[[3-[5-[[(2S)-3-hydroxy-3-methyl-1-(methylamino)-1-oxobutan-2-yl]carbamoyl]furan-2-yl]phenyl]methyl]-2-(trifluoromethyl)pyrimidine-4-carboxamide
• CAS: 1227192-35-9
• 化学式: C₂₄H₂₄F₃N₅O₅
• 分子量: 519.48
• InChiKey: KXNXODOVFJBDPH-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  146
• 氢给体数：
  4
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2-三氟甲基嘧啶-4-甲酸 、 在 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-[3-(5-{[(1S)-2-hydroxy-2-methyl-1-(methylcarbamoyl)propyl]carbamoyl}-2-furyl)benzyl]-2-(trifluoromethyl)pyrimidine-4-carboxamide
  参考文献：
  名称：

  SAR studies of non-zinc-chelating MMP-13 inhibitors: Improving selectivity and metabolic stability

  摘要：

  SAR studies to improve the selectivity and metabolic stability of a class of recently discovered MMP-13 inhibitors are reported. Improved selectivity was achieved by modifying interactions with the S1' pocket. Metabolic stability was improved through reduction of inhibitor lipophilicity. This translated into lower in vivo clearance for the preferred compound. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.07.036

文献信息

• Heteroaryl Diamide Compounds Useful as MMP-13 Inhibitors
  申请人：Farrow Neil Alexander

  公开号：US20110275625A1

  公开（公告）日：2011-11-10

  Disclosed are compounds and compositions of the formula (I) as described herein which are inhibitors of MMP-13. Also disclosed are methods of using and making compounds of the formula (I).

  本文披露了公式（I）所描述的化合物和组合物，它们是MMP-13的抑制剂。还披露了使用和制备公式（I）化合物的方法。
• HETEROARYL DIAMIDE COMPOUNDS USEFUL AS MMP-13 INHIBITORS
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP2346831B1

  公开（公告）日：2015-01-07
• US8637550B2
  申请人：——

  公开号：US8637550B2

  公开（公告）日：2014-01-28
• [EN] HETEROARYL DIAMIDE COMPOUNDS USEFUL AS MMP-13 INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROARYL-DIAMIDE UTILES EN TANT QU'INHIBITEURS DE MMP-13
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2010056585A2

  公开（公告）日：2010-05-20

  Disclosed are compounds and compositions of the formula (I) as described herein which are inhibitors of MMP-13. Also disclosed are methods of using and making compounds of the formula (I).
• SAR studies of non-zinc-chelating MMP-13 inhibitors: Improving selectivity and metabolic stability
  作者：Donghong Amy Gao、Zhaoming Xiong、Alexander Heim-Riether、Laura Amodeo、E. Michael August、Xianhua Cao、Leonard Ciccarelli、Brandon K. Collins、Kyle Harrington、Kathleen Haverty、Melissa Hill-Drzewi、Xiang Li、Shuang Liang、Steluta Mariana Margarit、Neil Moss、Nelamangala Nagaraja、John Proudfoot、Rene Roman、Sabine Schlyer、Lana Smith Keenan、Steven Taylor、Bernd Wellenzohn、Dieter Wiedenmayer、Jun Li、Neil A. Farrow

  DOI：10.1016/j.bmcl.2010.07.036

  日期：2010.9

  SAR studies to improve the selectivity and metabolic stability of a class of recently discovered MMP-13 inhibitors are reported. Improved selectivity was achieved by modifying interactions with the S1' pocket. Metabolic stability was improved through reduction of inhibitor lipophilicity. This translated into lower in vivo clearance for the preferred compound. (C) 2010 Elsevier Ltd. All rights reserved.