(4-amino-2-morpholin-4-yl-1,3-thiazol-5-yl)(3,4,5-trimethoxyphenyl)methanone | 1347690-14-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-amino-2-morpholin-4-yl-1,3-thiazol-5-yl)(3,4,5-trimethoxyphenyl)methanone
• 英文别名: (4-Amino-2-morpholin-4-yl-1,3-thiazol-5-yl)-(3,4,5-trimethoxyphenyl)methanone
• CAS: 1347690-14-5
• 化学式: C₁₇H₂₁N₃O₅S
• 分子量: 379.437
• InChiKey: YSJDWCYKTGJXBP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  124
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  吗啉 、 2-溴-1-(3,4,5-三甲氧基苯基)乙酮 、 N-氰亚胺基-S,S-二硫代碳酸二甲酯 在 sodiumsulfide nonahydrate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 以68%的产率得到(4-amino-2-morpholin-4-yl-1,3-thiazol-5-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  One-pot synthesis and biological evaluation of 2-pyrrolidinyl-4-amino-5-(3′,4′,5′-trimethoxybenzoyl)thiazole: A unique, highly active antimicrotubule agent

  摘要：

  A wide variety of small molecules with diverse molecular scaffolds inhibit microtubule formation. In this article we report a one-pot procedure for the preparation of a novel 2-(N-pyrrolidinyl)-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazole in which the size of the substituent at the C-2 position of the thiazole ring plays an essential role in compound activity. The most active agent (31) inhibited at sub-micromolar concentrations the growth of tumor cell lines. It also inhibited tubulin polymerization with an activity quantitatively similar to that of CA-4, and treatment of HeLa cells resulted in their arrest at the G2-M phase of the cell cycle. Furthermore, 3f was effective against multidrug resistant cancer cells and inhibited the growth of the HT-29 xenograft in a nude mouse model. This indicated that 31 is a promising new antimitotic agent with encouraging preclinical potential. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.10.013

文献信息

• One-pot synthesis and biological evaluation of 2-pyrrolidinyl-4-amino-5-(3′,4′,5′-trimethoxybenzoyl)thiazole: A unique, highly active antimicrotubule agent
  作者：Romeo Romagnoli、Pier Giovanni Baraldi、Carlota Lopez Cara、Maria Kimatrai Salvador、Roberta Bortolozzi、Giuseppe Basso、Giampietro Viola、Jan Balzarini、Andrea Brancale、Xian-Hua Fu、Jun Li、Su-Zhan Zhang、Ernest Hamel

  DOI：10.1016/j.ejmech.2011.10.013

  日期：2011.12

  A wide variety of small molecules with diverse molecular scaffolds inhibit microtubule formation. In this article we report a one-pot procedure for the preparation of a novel 2-(N-pyrrolidinyl)-4-amino-5-(3',4',5'-trimethoxybenzoyl)thiazole in which the size of the substituent at the C-2 position of the thiazole ring plays an essential role in compound activity. The most active agent (31) inhibited at sub-micromolar concentrations the growth of tumor cell lines. It also inhibited tubulin polymerization with an activity quantitatively similar to that of CA-4, and treatment of HeLa cells resulted in their arrest at the G2-M phase of the cell cycle. Furthermore, 3f was effective against multidrug resistant cancer cells and inhibited the growth of the HT-29 xenograft in a nude mouse model. This indicated that 31 is a promising new antimitotic agent with encouraging preclinical potential. (C) 2011 Elsevier Masson SAS. All rights reserved.