(S)-4-(2-(3-chlorophenyl)-2-hydroxyethylamino)-3-(6-(4-(3-fluoropropyl)piperazin-1-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one | 733734-15-1

• 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-(6-(4-(3-fluoropropyl)piperazin-1-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one
• 英文别名: 4-[[(2S)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]-3-[6-[4-(3-fluoropropyl)piperazin-1-yl]-4-methyl-1H-benzimidazol-2-yl]-1H-pyridin-2-one
• CAS: 733734-15-1
• 化学式: C₂₈H₃₂ClFN₆O₂
• 分子量: 539.052
• InChiKey: VUVAXIBXIAPBBM-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  38
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  96.5
• 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 、 1-溴-3-氟丙烷 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 生成 (S)-4-(2-(3-chlorophenyl)-2-hydroxyethylamino)-3-(6-(4-(3-fluoropropyl)piperazin-1-yl)-4-methyl-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

• Novel tyrosine kinase inhibitors
  申请人：——

  公开号：US20040044203A1

  公开（公告）日：2004-03-04

  The present invention provides compounds of formula I 1 and pharmaceutically acceptable salts thereof. The formula I compounds inhibit tyrosine kinase enzymes thereby making them useful as anti-cancer agents. The formula I compounds are also useful for the treatment of other diseases which can be treated by inhibiting tyrosine kinase enzymes.

  本发明提供了公式I1的化合物及其药用盐。公式I化合物抑制酪氨酸激酶酶，因此可用作抗癌剂。公式I化合物还可用于治疗其他可以通过抑制酪氨酸激酶酶来治疗的疾病。
• NOVEL TYROSINE KINASES INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1545543A2

  公开（公告）日：2005-06-29
• US7081454B2
  申请人：——

  公开号：US7081454B2

  公开（公告）日：2006-07-25
• US7223757B2
  申请人：——

  公开号：US7223757B2

  公开（公告）日：2007-05-29
• [EN] NOVEL TYROSINE KINASES INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE TYROSINE KINASES
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2004031401A2

  公开（公告）日：2004-04-15

  The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof. The formula (I) compounds inhibit tyrosine kinase enzymes thereby making them useful as anti-cancer agents.