(S)-4-(2-(3-chlorophenyl)-2-hydroxyethylamino)-3-(4-methyl-6-(4-(methylsulfonyl)piperazin-1-yl)-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one | 1232541-58-0

• 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)-4-(2-(3-chlorophenyl)-2-hydroxyethylamino)-3-(4-methyl-6-(4-(methylsulfonyl)piperazin-1-yl)-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one
• 英文别名: 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[4-methyl-6-(4-methylsulfonylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-pyridin-2-one
• CAS: 1232541-58-0
• 化学式: C₂₆H₂₉ClN₆O₄S
• 分子量: 557.073
• InChiKey: JNGUPQQSJDYXDB-JOCHJYFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  139
• 氢给体数：
  4
• 氢受体数：
  8

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 、 甲基磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-4-(2-(3-chlorophenyl)-2-hydroxyethylamino)-3-(4-methyl-6-(4-(methylsulfonyl)piperazin-1-yl)-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one
  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.