(S)-ethyl 4-(2-(4-(2-(3-chlorophenyl)-2-hydroxyethylamino)-2-oxo-1,2-dihydropyridin-3-yl)-4-methyl-1H-benzo[d]imidazol-6-yl)piperazine-1-carboxylate | 1232541-57-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: (S)-ethyl 4-(2-(4-(2-(3-chlorophenyl)-2-hydroxyethylamino)-2-oxo-1,2-dihydropyridin-3-yl)-4-methyl-1H-benzo[d]imidazol-6-yl)piperazine-1-carboxylate
• 英文别名: ethyl 4-[2-[4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-2-oxo-1H-pyridin-3-yl]-7-methyl-3H-benzimidazol-5-yl]piperazine-1-carboxylate
• CAS: 1232541-57-9
• 化学式: C₂₈H₃₁ClN₆O₄
• 分子量: 551.045
• InChiKey: LUCVGGOCKASWHT-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  123
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (S)-4-(2-(3-chlorophenyl)-2-hydroxyethylamino)-3-(4-methyl-6-(piperazin-1-yl)-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one 、 氯甲酸乙酯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-ethyl 4-(2-(4-(2-(3-chlorophenyl)-2-hydroxyethylamino)-2-oxo-1,2-dihydropyridin-3-yl)-4-methyl-1H-benzo[d]imidazol-6-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors: SAR of a series of 3-[6-(4-substituted-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one

  摘要：

  A series of 3-[6-(4-substitued-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one were synthesized to modulate CYP3A4 inhibition and improve aqueous solubility of our prototypical compound BMS-536924 (1), while maintaining potent IGF-1R inhibitory activity. Structure-activity and structure-solubility studies led to the identification of BMS-577098 (27), which demonstrates oral in vivo efficacy in animal models. The improvement was achieved by replacing morpholine with more polar bio-isoster piperazine and modulating the basicity of distal nitrogen with appropriate substitutions. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.057

文献信息

• Insulin-like growth factor-1 receptor (IGF-1R) kinase inhibitors: SAR of a series of 3-[6-(4-substituted-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one
  作者：Upender Velaparthi、Mark G. Saulnier、Mark D. Wittman、Peiying Liu、David B. Frennesson、Kurt Zimmermann、Joan M. Carboni、Marco Gottardis、Aixin Li、Ann Greer、Wendy Clarke、Zheng Yang、Krista Menard、Francis Y. Lee、George Trainor、Dolatrai Vyas

  DOI：10.1016/j.bmcl.2010.03.057

  日期：2010.5

  A series of 3-[6-(4-substitued-piperazin-1-yl)-4-methyl-1H-benzimidazol-2-yl]-1H-pyridine-2-one were synthesized to modulate CYP3A4 inhibition and improve aqueous solubility of our prototypical compound BMS-536924 (1), while maintaining potent IGF-1R inhibitory activity. Structure-activity and structure-solubility studies led to the identification of BMS-577098 (27), which demonstrates oral in vivo efficacy in animal models. The improvement was achieved by replacing morpholine with more polar bio-isoster piperazine and modulating the basicity of distal nitrogen with appropriate substitutions. (C) 2010 Elsevier Ltd. All rights reserved.