(S)-2-amino-1-(3-chloro-4-methoxyphenyl)ethanol | 767281-62-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (S)-2-amino-1-(3-chloro-4-methoxyphenyl)ethanol
• 英文别名: (1S)-2-amino-1-(3-chloro-4-methoxyphenyl)ethanol
• CAS: 767281-62-9
• 化学式: C₉H₁₂ClNO₂
• 分子量: 201.653
• InChiKey: FNZGVRAIYSDTRZ-MRVPVSSYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  55.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-1-(3-chloro-4-methoxyphenyl)ethanol 、 6-(1-(3-fluoropropyl)piperidin-4-yl)-2-(4-iodo-2-methoxypyridin-3-yl)-4-methyl-1H-benzo[d]imidazole 在 盐酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 乙腈 为溶剂， 反应 14.0h， 生成 (S)-4-(2-(3-chloro-4-methoxyphenyl)-2-hydroxyethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one
  参考文献：
  名称：

  Discovery and Evaluation of 4-(2-(4-chloro-1H-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1H-benzo[d]imidazol-2-yl)pyridin-2(1H)-one (BMS-695735), an Orally Efficacious Inhibitor of Insulin-like Growth Factor-1 Receptor Kinase with Broad Spectrum in Vivo Antitumor Activity

  摘要：

  We previously reported that 1 (BMS-536924), a benzimidazole inhibitor of the insulin-like growth factor-1 receptor, had demonstrated in vivo antitumor activity. This lead compound was found to have potent CYP3A4 inhibition, CYP3A4 induction mediated by PXR transactivation, poor aqueous solubility, and high plasma protein binding. Herein we disclose the evolution of this chemotype to address these issues. This effort led to 10 (BMS-695735), which exhibits improved ADME properties, a low risk for drug-drug interactions, and in vivo efficacy in multiple xenograft models.

  DOI：

  10.1021/jm800832q

文献信息

• THIAZOLYL COMPOUNDS USEFUL AS KINASE INHIBITORS
  申请人：Marinier Anne

  公开号：US20100048581A1

  公开（公告）日：2010-02-25

  The invention provides compounds of formula I [INSERT CHEMICAL STRUCTURE HERE] (I) and pharmaceutically acceptable salts thereof. The formula I thiazolyl compounds inhibit tyrosine kinase activity thereby making them useful as anticancer agents and for the treatment of Alzheimer's Disease.

  这项发明提供了化合物I的公式[插入化学结构在这里]（I）及其药学上可接受的盐。公式I的噻唑基化合物抑制酪氨酸激酶活性，因此可用作抗癌剂以及治疗阿尔茨海默病。
• US8148400B2
  申请人：——

  公开号：US8148400B2

  公开（公告）日：2012-04-03
• Discovery and Evaluation of 4-(2-(4-chloro-1<i>H</i>-pyrazol-1-yl)ethylamino)-3-(6-(1-(3-fluoropropyl)piperidin-4-yl)-4-methyl-1<i>H</i>-benzo[<i>d</i>]imidazol-2-yl)pyridin-2(1<i>H</i>)-one (BMS-695735), an Orally Efficacious Inhibitor of Insulin-like Growth Factor-1 Receptor Kinase with Broad Spectrum in Vivo Antitumor Activity
  作者：Upender Velaparthi、Mark Wittman、Peiying Liu、Joan M. Carboni、Francis Y. Lee、Ricardo Attar、Praveen Balimane、Wendy Clarke、Michael W. Sinz、Warren Hurlburt、Karishma Patel、Lorell Discenza、Sean Kim、Marco Gottardis、Ann Greer、Aixin Li、Mark Saulnier、Zheng Yang、Kurt Zimmermann、George Trainor、Dolatrai Vyas

  DOI：10.1021/jm800832q

  日期：2008.10.9

  We previously reported that 1 (BMS-536924), a benzimidazole inhibitor of the insulin-like growth factor-1 receptor, had demonstrated in vivo antitumor activity. This lead compound was found to have potent CYP3A4 inhibition, CYP3A4 induction mediated by PXR transactivation, poor aqueous solubility, and high plasma protein binding. Herein we disclose the evolution of this chemotype to address these issues. This effort led to 10 (BMS-695735), which exhibits improved ADME properties, a low risk for drug-drug interactions, and in vivo efficacy in multiple xenograft models.