4-methyl-2-(4-fluorophenyl)thiazole-5-carbonyl chloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 4-methyl-2-(4-fluorophenyl)thiazole-5-carbonyl chloride
• 英文别名: 2-(4-Fluorophenyl)-4-methyl-1,3-thiazole-5-carbonyl chloride；2-(4-fluorophenyl)-4-methyl-1,3-thiazole-5-carbonyl chloride
• 化学式: C₁₁H₇ClFNOS
• 分子量: 255.7
• InChiKey: BVRRJQQAJXTOTC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  58.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-methyl-2-(4-fluorophenyl)thiazole-5-carbonyl chloride 在 sodium hydroxide 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 2-methyl-2-[4-{[(4-methyl-2-[4-fluorophenyl]-thiazol-5-ylcarbonyl)amino]methyl}phenoxy]propionic acid
  参考文献：
  名称：

  Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents

  摘要：

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.

  DOI：

  10.1021/jm058056x
• 作为产物：
  描述：

  ethyl 2-(4-fluorophenyl)-4-methylthiazole-5-carboxylate 在 sodium hydroxide 、 氯化亚砜 作用下， 以 乙醇 、 水 为溶剂， 反应 4.5h， 生成 4-methyl-2-(4-fluorophenyl)thiazole-5-carbonyl chloride
  参考文献：
  名称：

  Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents

  摘要：

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.

  DOI：

  10.1021/jm058056x

文献信息

• 噻唑-5-甲酰胺化合物、及其制法和药物组合物 与用途
  申请人：中国医学科学院药物研究所

  公开号：CN102532123B

  公开（公告）日：2016-03-09

  本发明涉及通式I的新的2-苯基噻唑-5-甲酰胺化合物、其前体、立体异构体和生理上可接受的盐、含有所述化合物的药物组合物以及在医药方面的应用。
• Design, synthesis and biological evaluation of 4-phenoxy-pyridine/pyrimidine derivatives as dual VEGFR-2/c-Met inhibitors
  作者：Feiyi Yang、Qian Zhang、Qiuyan Guo、Qingshan Pan、Chunping Wen、Xinya Lv、Wufu Zhu、Pengwu Zheng

  DOI：10.1039/d2nj01561g

  日期：——

  A class of 4-phenoxy-pyridine/pyrimidine derivatives (23a–23p and 24a–24h) were designed, synthesized and evaluated as potent dual VEGFR-2/c-Met inhibitors. The in vitro anti-cancer cell proliferative activity of the compounds indicated that compound 23k was regarded as a promising derivative. Compared to the lead compounds Foretinib and Sorafenib, 23k showed excellent inhibitory activity against the

  设计、合成和评估了一类 4-苯氧基-吡啶/嘧啶衍生物（23a-23p和24a-24h ）作为有效的双重 VEGFR-2/c-Met 抑制剂。化合物的体外抗癌细胞增殖活性表明化合物23k被认为是一种有前途的衍生物。与先导化合物 Foretinib 和 Sorafenib 相比，23k对 A549、MCF-7、HepG2 和 Ovcar-3 细胞系表现出优异的抑制活性，IC 50值为 2.16 ± 0.19 μM、9.13 ± 0.65 μM、20.15 ± 2.64 和 9.65 ±分别为 0.51 μM。此外，23k对人类正常细胞（LO2 细胞）表现出低毒性，IC 50值高于 100 μM。在激酶测定中，最有希望的化合物23k显示出优异的激酶抑制活性和对 VEGFR-2 和 c-Met 的选择性，IC 50值分别为 1.05 和 1.43 μM。进一步的活性​​研究表明，23k不仅诱导 A549
• Substituted 2-[(4-Aminomethyl)phenoxy]-2-methylpropionic Acid PPARα Agonists. 1. Discovery of a Novel Series of Potent HDLc Raising Agents
  作者：Michael L. Sierra、Véronique Beneton、Anne-Bénédict Boullay、Thierry Boyer、Andrew G. Brewster、Frédéric Donche、Marie-Claire Forest、Marie-Hélène Fouchet、Françoise J. Gellibert、Didier A. Grillot、Millard H. Lambert、Alain Laroze、Christelle Le Grumelec、Jean Michel Linget、Valerie G. Montana、Van-Loc Nguyen、Edwige Nicodème、Vipul Patel、Annie Penfornis、Olivier Pineau、Danig Pohin、Florent Potvain、Géraldine Poulain、Cécile Bertho Ruault、Michael Saunders、Jérôme Toum、H. Eric Xu、Robert X. Xu、Pascal M. Pianetti

  DOI：10.1021/jm058056x

  日期：2007.2.1

  The peroxisome proliferator activated receptors PPAR alpha, PPAR gamma, and PPAR delta are ligand-activated transcription factors that play a key role in lipid homeostasis. The fibrates raise circulating levels of high-density lipoprotein cholesterol and lower levels of triglycerides in part through their activity as PPAR alpha agonists; however, the low potency and restricted selectivity of the fibrates may limit their efficacy, and it would be desirable to develop more potent and selective PPAR alpha agonists. Modification of the selective PPAR delta agonist 1 (GW501516) so as to incorporate the 2-aryl-2-methylpropionic acid group of the fibrates led to a marked shift in potency and selectivity toward PPAR alpha agonism. Optimization of the series gave 25a, which shows EC50 = 4 nM on PPAR alpha and at least 500-fold selectivity versus PPAR delta and PPAR gamma. Compound 25a (GW590735) has been progressed to clinical trials for the treatment of diseases of lipid imbalance.