2-chloro-N-(4'-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1'-biphenyl-3-yl)isonicotinamide | 515812-24-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-chloro-N-(4'-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1'-biphenyl-3-yl)isonicotinamide
• 英文别名: 2-chloro-N-[3-[4-(cyclopropylmethylcarbamoyl)phenyl]-4-methylphenyl]pyridine-4-carboxamide
• CAS: 515812-24-5
• 化学式: C₂₄H₂₂ClN₃O₂
• 分子量: 419.911
• InChiKey: AKNCGPVDTHDMNT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  71.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-N-(4'-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1'-biphenyl-3-yl)isonicotinamide 在 水 作用下， 以 环丙基甲胺 为溶剂， 反应 96.0h， 以to give 2-(cyclopropylmethylamino)-N-(4′-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1′-biphenyl-3-yl)isonicotinamide (17.1 mg, 32%)的产率得到2-(cyclopropylmethylamino)-N-(4'-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1'-biphenyl-3-yl)isonicotinamide
  参考文献：
  名称：

  5-acylamino-1,1'-biphenyl-4-carboxamide derivatives and their use as p38 kinase inhibitors

  摘要：

  化学式为(I)的化合物1或其药学上可接受的盐或溶剂，以及它们作为药物的用途，特别是作为p38激酶抑制剂。

  公开号：

  US20040242868A1
• 作为产物：
  描述：

  2-氯吡啶-4-甲酰氯 、 5'-amino-N-(cyclopropylmethyl)-2'-methyl-1,1'-biphenyl-4-carboxamide 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以33%的产率得到2-chloro-N-(4'-{[(cyclopropylmethyl)amino]carbonyl}-6-methyl-1,1'-biphenyl-3-yl)isonicotinamide
  参考文献：
  名称：

  Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes

  摘要：

  The biphenyl amides (BPAs) are a series of p38alpha MAP kinase inhibitors. Compounds are able to bind to the kinase in either the DFG-in or DFG-out conformation, depending on substituents. X-ray, binding, kinetic and cellular data are shown, providing the most detailed comparison to date between potent compounds from the same chemical series that bind to different p38alpha conformations. DFG-out-binding compounds could be made more potent than DFG-in-binding compounds by increasing their size. Unexpectedly, compounds that bound to the DGF-out conformation showed diminished selectivity. The kinetics of binding to the isolated enzyme and the effects of compounds on cells were largely unaffected by the kinase conformation bound.

  DOI：

  10.1016/j.bmcl.2008.06.028

文献信息

• 5-acylamino-1,1'-biphenyl-4-carboxamide derivatives and their use as p38 kinase inhibitors
  申请人：——

  公开号：US20040242868A1

  公开（公告）日：2004-12-02

  Compounds of formula (I): 1 or pharmaceutically acceptable salts or solvates thereof, and their use as pharmaceuticals, particularly as p38 kinase inhibitors.

  化学式为(I)的化合物1或其药学上可接受的盐或溶剂，以及它们作为药物的用途，特别是作为p38激酶抑制剂。
• 5'-ACYLAMINO-1,1'-BIPHENYL-4-CARBOXAMIDE DERIVATIVES AND THEIR USE AS P38 KINASE INHIBITORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1435934A1

  公开（公告）日：2004-07-14
• US7432289B2
  申请人：——

  公开号：US7432289B2

  公开（公告）日：2008-10-07
• [EN] 5'-ACYLAMINO-1,1'-BIPHENYL-4-CARBOXAMIDE DERIVATIVES AND THEIR USE AS P38 KINASE INHIBITORS<br/>[FR] DERIVES DE 5'-ACYLAMINO-1,1'-BIPHENYL-4-CARBOXAMIDE ET LEUR UTILISATION COMME INHIBITEURS DE LA KINASE P 38
  申请人：GLAXO GROUP LTD

  公开号：WO2003032971A1

  公开（公告）日：2003-04-24

  Compounds of formula (I): wherein R3 is the group -NH-CO-R6; or pharmaceutically acceptable salts or solvates thereof, and their use as pharmaceuticals, particularly as p38 kinase inhibitors.
• Biphenyl amide p38 kinase inhibitors 4: DFG-in and DFG-out binding modes
  作者：Richard M. Angell、Tony D. Angell、Paul Bamborough、Mark J. Bamford、Chun-wa Chung、Stuart G. Cockerill、Stephen S. Flack、Katherine L. Jones、Dramane I. Laine、Timothy Longstaff、Steve Ludbrook、Rosannah Pearson、Kathryn J. Smith、Penny A. Smee、Don O. Somers、Ann L. Walker

  DOI：10.1016/j.bmcl.2008.06.028

  日期：2008.8

  The biphenyl amides (BPAs) are a series of p38alpha MAP kinase inhibitors. Compounds are able to bind to the kinase in either the DFG-in or DFG-out conformation, depending on substituents. X-ray, binding, kinetic and cellular data are shown, providing the most detailed comparison to date between potent compounds from the same chemical series that bind to different p38alpha conformations. DFG-out-binding compounds could be made more potent than DFG-in-binding compounds by increasing their size. Unexpectedly, compounds that bound to the DGF-out conformation showed diminished selectivity. The kinetics of binding to the isolated enzyme and the effects of compounds on cells were largely unaffected by the kinase conformation bound.