4-(6-Chloro-pyrimidin-4-ylamino)-N-[4-(2-fluoro-3-trifluoromethyl-phenyl)-thiazol-2-yl]-benzamide | 881400-37-9

• 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-(6-Chloro-pyrimidin-4-ylamino)-N-[4-(2-fluoro-3-trifluoromethyl-phenyl)-thiazol-2-yl]-benzamide
• 英文别名: 4-[(6-chloropyrimidin-4-yl)amino]-N-[4-[2-fluoro-3-(trifluoromethyl)phenyl]-1,3-thiazol-2-yl]benzamide
• CAS: 881400-37-9
• 化学式: C₂₁H₁₂ClF₄N₅OS
• 分子量: 493.872
• InChiKey: SMYBXNOVTIROQA-UHFFFAOYSA-N

物化性质

• 密度：
  1.550±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-(6-Chloro-pyrimidin-4-ylamino)-N-[4-(2-fluoro-3-trifluoromethyl-phenyl)-thiazol-2-yl]-benzamide 、 氮杂环丁烷-3-醇 在 N-甲基吡咯烷酮 作用下， 生成 N-(4-(2-fluoro-3-(trifluoromethyl)phenyl)thiazol-2-yl)-4-(6-(3-hydroxyazetidin-1-yl)pyrimidin-4-ylamino)benzamide
  参考文献：
  名称：

  Pyrimidine benzamide-based thrombopoietin receptor agonists

  摘要：

  A series of pyrimidine benzamide-based thrombopoietin receptor agonists is described. The lead molecule contains a 2-amino-5-unsubstituted thiazole, a group that has been associated with idiosyncratic toxicity. The potential for metabolic oxidation at C-5 of the thiazole, the likely source of toxic metabolites, was removed by substitution at C-5 or by replacing the thiazole with a thiadiazole. Potency in the series was improved by modifying the substituents on the pyrimidine and/or on the thiazole or thiadiazole pendant aryl ring. In vivo examination revealed that compounds from the series are not highly bioavailable. This is attributed to low solubility and poor permeability. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.038
• 作为产物：
  描述：

  4-[(6-Chloropyrimidin-4-yl)amino]benzoyl chloride 、 4-(2-fluoro-3-(trifluoromethyl)phenyl)thiazol-2-amine 在 吡啶 作用下， 生成 4-(6-Chloro-pyrimidin-4-ylamino)-N-[4-(2-fluoro-3-trifluoromethyl-phenyl)-thiazol-2-yl]-benzamide
  参考文献：
  名称：

  Pyrimidine benzamide-based thrombopoietin receptor agonists

  摘要：

  A series of pyrimidine benzamide-based thrombopoietin receptor agonists is described. The lead molecule contains a 2-amino-5-unsubstituted thiazole, a group that has been associated with idiosyncratic toxicity. The potential for metabolic oxidation at C-5 of the thiazole, the likely source of toxic metabolites, was removed by substitution at C-5 or by replacing the thiazole with a thiadiazole. Potency in the series was improved by modifying the substituents on the pyrimidine and/or on the thiazole or thiadiazole pendant aryl ring. In vivo examination revealed that compounds from the series are not highly bioavailable. This is attributed to low solubility and poor permeability. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.038

文献信息

• Thrombopoietin Receptor Agonists
  申请人：Reiter Lawrence A.

  公开号：US20080076771A1

  公开（公告）日：2008-03-27

  A compound of the formula (I) useful as promoters of thrombopoiesis and megakaryocytopoiesis, wherein A, B, D, E, W, X, Y, Z, R 1 and R 2 are defined as above.

  一种化合物，其化学式为（I），可用作促进血小板生成和巨核细胞生成的促进剂，其中A、B、D、E、W、X、Y、Z、R1和R2如上所定义。
• TROMBOPOIETIN RECEPTOR AGONISTS
  申请人：Pfizer Products Incorporated

  公开号：EP1794156A2

  公开（公告）日：2007-06-13
• [EN] TROMBOPOIETIN RECEPTOR AGONISTS<br/>[FR] AGONISTES DU RECEPTEUR DE THROMBOPOIETINE
  申请人：PFIZER PROD INC

  公开号：WO2006033005A2

  公开（公告）日：2006-03-30

  A compound of the formula (I) useful as promoters of thrombopoiesis and megakaryocytopoiesis, wherein A, B, D, E, W, X, Y, Z, R1 and R2 are defined as above.