4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(1H-tetrazol-5-ylmethyl)-phenyl]-amide | 915006-59-6

• 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-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(1H-tetrazol-5-ylmethyl)-phenyl]-amide
• 英文别名: 4-cyano-N-[2-(4,4-dimethylcyclohexen-1-yl)-4-(2H-tetrazol-5-ylmethyl)phenyl]-1-(2-trimethylsilylethoxymethyl)imidazole-2-carboxamide
• CAS: 915006-59-6
• 化学式: C₂₇H₃₆N₈O₂Si
• 分子量: 532.721
• InChiKey: FRRMLKIBAOOMMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.02
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(1H-tetrazol-5-ylmethyl)-phenyl]-amide 在 三氟乙酸 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 生成 5-cyano-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(1H-tetrazol-5-ylmethyl)-phenyl]-amide
  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
• 作为产物：
  描述：

  对氨基苯乙腈 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 三甲基甲硅烷基锡 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 6.0h， 生成 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [2-(4,4-dimethyl-cyclohex-1-enyl)-4-(1H-tetrazol-5-ylmethyl)-phenyl]-amide
  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。
• WO2007/123516
  申请人：——

  公开号：——

  公开（公告）日：——
• 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.