N1-5-[4-([(5-methyl-3-isoxazolyl)amino]carbonylamino)phenyl]-1,3-thiazol-2-yl-4-(2-morpholinoethoxy)benzamide | 1395051-45-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N1-5-[4-([(5-methyl-3-isoxazolyl)amino]carbonylamino)phenyl]-1,3-thiazol-2-yl-4-(2-morpholinoethoxy)benzamide
• 英文别名: N-[5-[4-[(5-methyl-1,2-oxazol-3-yl)carbamoylamino]phenyl]-1,3-thiazol-2-yl]-4-(2-morpholin-4-ylethoxy)benzamide
• CAS: 1395051-45-2
• 化学式: C₂₇H₂₈N₆O₅S
• 分子量: 548.623
• InChiKey: BRQRIWCNAPETPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  39
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  159
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-[2-(morpholin-4-yl)ethoxy]benzoyl chloride 、 5-(4-aminophenyl)-1,3-thiazol-2-amine 在 吡啶 作用下， 反应 4.0h， 生成 N1-5-[4-([(5-methyl-3-isoxazolyl)amino]carbonylamino)phenyl]-1,3-thiazol-2-yl-4-(2-morpholinoethoxy)benzamide
  参考文献：
  名称：

  Identification of a potent 5-phenyl-thiazol-2-ylamine-based inhibitor of FLT3 with activity against drug resistance-conferring point mutations

  摘要：

  Numerous FLT3 inhibitors have been explored as a viable therapy for the treatment of acute myeloid leukemia (AML). However, clinical data have been underwhelming due to incomplete inhibition of FLT3 or the emergence of resistant mutations treated with these older agents. We previously developed a series of 3-phenyl-1H-5-pyrazolylamine derivatives as highly potent and selective FLT3 inhibitors with good in vivo efficacy using an intravenous (IV) route. However, the poor bioavailability of these pyrazole compounds limits the development of these promising antileukemic compounds for clinical use. Herein, we describe a novel class of 5-phenyl-thiazol-2-ylamine compounds that are multi-targeted FLT3 inhibitors. From this class of compounds, compound 7h was very potent against AML cell lines and exhibited excellent oral efficacy in AML xenograft models. In addition, further studies demonstrated that compound 7h exhibited potent in vitro and in vivo activities against clinically relevant AC220 (3)-resistant kinase domain mutants of FLT3-ITD. (C) 2015 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.05.008

文献信息

• PYRAZOLE COMPOUNDS AND THIAZOLE COMPOUNDS AS PROTEIN KINASES INHIBITORS
  申请人：Jiaang Weir-Torn

  公开号：US20120225880A1

  公开（公告）日：2012-09-06

  A compound of formula (I): wherein A, B, D, X, Y, R 1 , R 2 , R 3 , m, p, and q are defined herein. Also disclosed is a method for inhibiting FMS-like tyrosine kinase 3, aurora kinase, or vascular endothelial growth factor receptor.

  其中A、B、D、X、Y、R1、R2、R3、m、p和q的化合物的化学式（I）： 还公开了一种抑制FMS样酪氨酸激酶3、极光激酶或血管内皮生长因子受体的方法。
• US9255072B2
  申请人：——

  公开号：US9255072B2

  公开（公告）日：2016-02-09
• Identification of a potent 5-phenyl-thiazol-2-ylamine-based inhibitor of FLT3 with activity against drug resistance-conferring point mutations
  作者：Chiung-Tong Chen、John T.-A. Hsu、Wen-Hsing Lin、Cheng-Tai Lu、Shih-Chieh Yen、Tsu Hsu、Yu-Ling Huang、Jen-Shin Song、Chun-Hwa Chen、Ling-Hui Chou、Kuei-Jung Yen、Ching-Ping Chen、Po-Chu Kuo、Chen-Lung Huang、H. Eugene Liu、Yu-Sheng Chao、Teng-Kuang Yeh、Weir-Torn Jiaang

  DOI：10.1016/j.ejmech.2015.05.008

  日期：2015.7

  Numerous FLT3 inhibitors have been explored as a viable therapy for the treatment of acute myeloid leukemia (AML). However, clinical data have been underwhelming due to incomplete inhibition of FLT3 or the emergence of resistant mutations treated with these older agents. We previously developed a series of 3-phenyl-1H-5-pyrazolylamine derivatives as highly potent and selective FLT3 inhibitors with good in vivo efficacy using an intravenous (IV) route. However, the poor bioavailability of these pyrazole compounds limits the development of these promising antileukemic compounds for clinical use. Herein, we describe a novel class of 5-phenyl-thiazol-2-ylamine compounds that are multi-targeted FLT3 inhibitors. From this class of compounds, compound 7h was very potent against AML cell lines and exhibited excellent oral efficacy in AML xenograft models. In addition, further studies demonstrated that compound 7h exhibited potent in vitro and in vivo activities against clinically relevant AC220 (3)-resistant kinase domain mutants of FLT3-ITD. (C) 2015 Published by Elsevier Masson SAS.