5-(bromomethyl)-2-(4-chlorophenyl)-4-methylthiazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(bromomethyl)-2-(4-chlorophenyl)-4-methylthiazole
• 英文别名: 5-(Bromomethyl)-2-(4-chlorophenyl)-4-methyl-1,3-thiazole；5-(bromomethyl)-2-(4-chlorophenyl)-4-methyl-1,3-thiazole
• 化学式: C₁₁H₉BrClNS
• 分子量: 302.622
• InChiKey: STEJHGKWPHMFPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  41.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(bromomethyl)-2-(4-chlorophenyl)-4-methylthiazole 在 potassium phtalimide 、 一水合肼 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-(4-chlorophenyl)-4-methylthiazol-5-yl methylamine
  参考文献：
  名称：

  Design and optimization of hybrid of 2,4-diaminopyrimidine and arylthiazole scaffold as anticancer cell proliferation and migration agents

  摘要：

  Therapeutics of metastatic or triple-negative breast cancer are still challenging in clinical. Herein we demonstrated the design and optimization of a series of hybrid of 2,4-diaminopyrimidine and arylthiazole derivatives for their anti-proliferative properties against two breast cancer cell lines (MCF-7 as human breast cancer and MDA-MB-231 as triple-negative breast cancer). More importantly, some of those compounds with potent antiproliferative activities also indicated excellent inhibitory activities against MDA-MB-231 cell migration. These results suggested that the new series of hybridation of arylthiazoles and aminopyrimidines could be identified and developed as novel highly potential anticancer agents against the triple-negative breast cancer as well as metastatic one in the future. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.027
• 作为产物：
  描述：

  4-氯硫代苯甲酰胺 在 吡啶 、 lithium aluminium tetrahydride 、 三溴化磷 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 生成 5-(bromomethyl)-2-(4-chlorophenyl)-4-methylthiazole
  参考文献：
  名称：

  Design and optimization of hybrid of 2,4-diaminopyrimidine and arylthiazole scaffold as anticancer cell proliferation and migration agents

  摘要：

  Therapeutics of metastatic or triple-negative breast cancer are still challenging in clinical. Herein we demonstrated the design and optimization of a series of hybrid of 2,4-diaminopyrimidine and arylthiazole derivatives for their anti-proliferative properties against two breast cancer cell lines (MCF-7 as human breast cancer and MDA-MB-231 as triple-negative breast cancer). More importantly, some of those compounds with potent antiproliferative activities also indicated excellent inhibitory activities against MDA-MB-231 cell migration. These results suggested that the new series of hybridation of arylthiazoles and aminopyrimidines could be identified and developed as novel highly potential anticancer agents against the triple-negative breast cancer as well as metastatic one in the future. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.04.027

文献信息

• Discovery of Pyrrolidine-Containing GPR40 Agonists: Stereochemistry Effects a Change in Binding Mode
  作者：Elizabeth A. Jurica、Ximao Wu、Kristin N. Williams、Andres S. Hernandez、David S. Nirschl、Richard A. Rampulla、Arvind Mathur、Min Zhou、Gary Cao、Chunshan Xie、Biji Jacob、Hong Cai、Tao Wang、Brian J. Murphy、Heng Liu、Carrie Xu、Lori K. Kunselman、Michael B. Hicks、Qin Sun、Dora M. Schnur、Doree F. Sitkoff、Elizabeth A. Dierks、Atsu Apedo、Douglas B. Moore、Kimberly A. Foster、Mary Ellen Cvijic、Reshma Panemangalore、Neil A. Flynn、Brad D. Maxwell、Yang Hong、Yuan Tian、Jason J. Wilkes、Bradley A. Zinker、Jean M. Whaley、Joel C. Barrish、Jeffrey A. Robl、William R. Ewing、Bruce A. Ellsworth

  DOI：10.1021/acs.jmedchem.6b01559

  日期：2017.2.23

  A novel series of pyrrolidine-containing GPR40 agonists is described as a potential treatment for type 2 diabetes. The initial pyrrolidine hit was modified by moving the position of the carboxylic acid, a key pharmacophore for GPR40. Addition of a 4-cis-CF3 to the pyrrolidine improves the human GPR40 binding K-i and agonist efficacy. After further optimization, the discovery of a minor enantiomeric impurity with agonist activity led to the finding that enantiomers (R,R)-68 and (S,S)-68 have differential effects on the radioligand used for the binding assay, with (R,R)-68 potentiating the radioligand and (S,S)-68 displacing the radioligand. Compound (R,R)-68 activates both G(q)-coupled intracellular Ca2+ flux and G(s)-coupled cAMP accumulation. This signaling bias results in a dual mechanism of action for compound (R,R)-68, demonstrating glucose-dependent insulin and GLP-1 secretion in vitro. In vivo, compound (R,R)-68 significantly lowers plasma glucose levels in mice during an oral glucose challenge, encouraging further development of the series.
• Design and optimization of hybrid of 2,4-diaminopyrimidine and arylthiazole scaffold as anticancer cell proliferation and migration agents
  作者：Wenbo Zhou、Anling Huang、Yong Zhang、Qingxiang Lin、Weikai Guo、Zihua You、Zhengfang Yi、Mingyao Liu、Yihua Chen

  DOI：10.1016/j.ejmech.2015.04.027

  日期：2015.5

  Therapeutics of metastatic or triple-negative breast cancer are still challenging in clinical. Herein we demonstrated the design and optimization of a series of hybrid of 2,4-diaminopyrimidine and arylthiazole derivatives for their anti-proliferative properties against two breast cancer cell lines (MCF-7 as human breast cancer and MDA-MB-231 as triple-negative breast cancer). More importantly, some of those compounds with potent antiproliferative activities also indicated excellent inhibitory activities against MDA-MB-231 cell migration. These results suggested that the new series of hybridation of arylthiazoles and aminopyrimidines could be identified and developed as novel highly potential anticancer agents against the triple-negative breast cancer as well as metastatic one in the future. (C) 2015 Elsevier Masson SAS. All rights reserved.