(S)-tert-butyl 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 | 741244-97-3

• 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)-tert-butyl 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: tert-butyl 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: 741244-97-3
• 化学式: C₃₀H₃₅ClN₆O₄
• 分子量: 579.099
• InChiKey: WDPFLACZLYWILA-XMMPIXPASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  41
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  123
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 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 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-4-(2-(3-chlorophenyl)-2-hydroxyethylamino)-3-(4-methyl-6-(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
• 作为产物：
  描述：

  4-[2-(4-iodo-2-oxo-1,2-dihydro-pyridin-3-yl)-7-methyl-3H-benzoimidazol-5-yl]-piperazine-1-carboxylic acid tert-butyl ester 、 (S)-2-氨基-1-(3-氯苯基)-乙醇 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 以70%的产率得到(S)-tert-butyl 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

• 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。
• [EN] NOVEL TYROSINE KINASE INHIBITORS<br/>[FR] NOUVEAUX INHIBITEURS DE LA TYROSINE KINASE
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2002079192A1

  公开（公告）日：2002-10-10

  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. 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I[ ]式化合物及其药学上可接受的盐。I式化合物抑制酪氨酸激酶酶，因此可用作抗癌剂。I式化合物也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。
• EP1381598A4
  申请人：——

  公开号：EP1381598A4

  公开（公告）日：2008-03-19
• NOVEL TYROSINE KINASE INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1381598A1

  公开（公告）日：2004-01-21
• NOVEL TYROSINE KINASES INHIBITORS
  申请人：Bristol-Myers Squibb Company

  公开号：EP1545543A2

  公开（公告）日：2005-06-29