4-[(4-cyano-1H-imidazole-2-carbonyl)-amino]-3-(4,4-dimethyl-cyclohex-1-enyl)-benzoic acid

• 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: 4-[(4-cyano-1H-imidazole-2-carbonyl)-amino]-3-(4,4-dimethyl-cyclohex-1-enyl)-benzoic acid
• 英文别名: 4-[(5-cyano-1H-imidazole-2-carbonyl)amino]-3-(4,4-dimethylcyclohexen-1-yl)benzoic acid
• 化学式: C₂₀H₂₀N₄O₃
• 分子量: 364.404
• InChiKey: MQEMXHCRAIJXMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[(4-cyano-1H-imidazole-2-carbonyl)-amino]-3-(4,4-dimethyl-cyclohex-1-enyl)-benzoic acid 、 D-glutamic acid diethyl ester hydrochloride 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成
  参考文献：
  名称：

  WO2007/123516

  摘要：

  公开号：
• 作为产物：
  描述：

  4 -溴- 2 - 碘苯甲胺 在 四(三苯基膦)钯 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 异丙基氯化镁 、 sodium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 potassium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 5.92h， 生成 4-[(4-cyano-1H-imidazole-2-carbonyl)-amino]-3-(4,4-dimethyl-cyclohex-1-enyl)-benzoic acid
  参考文献：
  名称：

  Enhancement of kinase selectivity in a potent class of arylamide FMS inhibitors

  摘要：

  Structure-activity relationship (SAR) studies on a highly potent series of arylamide FMS inhibitors were carried out with the aim of improving FMS kinase selectivity, particularly over KIT. Potent compound 17r (FMS IC50 0.7 nM, FMS cell IC50 6.1 nM) was discovered that had good PK properties and a greater than fivefold improvement in selectivity for FMS over KIT kinase in a cellular assay relative to the previously reported clinical candidate 4. This improved selectivity was manifested in vivo by no observed decrease in circulating reticulocytes, a measure of bone safety, at the highest studied dose. Compound 17r was highly active in a mouse pharmacodynamic model and demonstrated disease-modifying effects in a dose-dependent manner in a strep cell wall-induced arthritis model of rheumatoid arthritis in rats. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.09.061

文献信息

• c-fms kinase inhibitors
  申请人：Player R. Mark

  公开号：US20060258666A1

  公开（公告）日：2006-11-16

  The invention is directed to compounds of Formula II: wherein A, R 1 , R 2 , R 3 , R 4 , X, Y and W are set forth in the specification, as well as solvates, hydrates, tautomers or pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase.

  本发明涉及公式II的化合物： 其中A、R1、R2、R3、R4、X、Y和W在说明书中有所阐述，以及其溶剂化物、水合物、互变异构体或药学上可接受的盐，其可抑制蛋白酪氨酸激酶，特别是c-fms激酶。
• C-FMS KINASE INHIBITORS
  申请人：Janssen Pharmaceutica NV

  公开号：EP2016057A1

  公开（公告）日：2009-01-21
• US7790724B2
  申请人：——

  公开号：US7790724B2

  公开（公告）日：2010-09-07
• [EN] C-FMS KINASE INHIBITORS<br/>[FR] Inhibiteurs de la c-fms kinase
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2007123516A1

  公开（公告）日：2007-11-01

  [EN] The invention is directed to compounds of Formula II: wherein A, R₁, R₂, R₃, R₄, X, Y and W are set forth in the specification, as well as solvates, hydrates, tautomers or pharmaceutically acceptable salts thereof, that inhibit protein tyrosine kinases, especially c-fms kinase.
  [FR] L'invention concerne des composés de Formule II dans laquelle A, R₁, R₂, R₃, R₄, X, Y et W sont définis dans la description ainsi que des solvates, des hydrates, des tautomères ou des sels pharmaceutiquement acceptables de ceux-ci qui inhibent les protéine tyrosine kinases, notamment la c-fms kinase.
• Enhancement of kinase selectivity in a potent class of arylamide FMS inhibitors
  作者：Carl R. Illig、Carl L. Manthey、Sanath K. Meegalla、Mark J. Wall、Jinsheng Chen、Kenneth J. Wilson、Renee L. DesJarlais、Shelley K. Ballentine、Carsten Schubert、Carl S. Crysler、Yanmin Chen、Christopher J. Molloy、Margery A. Chaikin、Robert R. Donatelli、Edward Yurkow、Zhao Zhou、Mark R. Player、Bruce E. Tomczuk

  DOI：10.1016/j.bmcl.2013.09.061

  日期：2013.12

  Structure-activity relationship (SAR) studies on a highly potent series of arylamide FMS inhibitors were carried out with the aim of improving FMS kinase selectivity, particularly over KIT. Potent compound 17r (FMS IC50 0.7 nM, FMS cell IC50 6.1 nM) was discovered that had good PK properties and a greater than fivefold improvement in selectivity for FMS over KIT kinase in a cellular assay relative to the previously reported clinical candidate 4. This improved selectivity was manifested in vivo by no observed decrease in circulating reticulocytes, a measure of bone safety, at the highest studied dose. Compound 17r was highly active in a mouse pharmacodynamic model and demonstrated disease-modifying effects in a dose-dependent manner in a strep cell wall-induced arthritis model of rheumatoid arthritis in rats. (C) 2013 Elsevier Ltd. All rights reserved.