4-Methyl-2-pyridin-4-yl-1,3-thiazole-5-carbonyl chloride | 892502-18-0

• 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-pyridin-4-yl-1,3-thiazole-5-carbonyl chloride
• CAS: 892502-18-0
• 化学式: C₁₀H₇ClN₂OS
• 分子量: 238.697
• InChiKey: RABMJRMSTJUPEX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-amino-5-[2,4-bis(benzyloxy)-5-isopropylphenyl]isoxazole-3-carboxylic acid ethylamide 、 4-Methyl-2-pyridin-4-yl-1,3-thiazole-5-carbonyl chloride 在 三氯化硼 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.17h， 生成 5-(2,4-dihydroxy-5-isopropylphenyl)-4-[(4-methyl-2-pyridin-4-ylthiazole-5-carbonyl)amino]isoxazole-3-carboxylic acid ethylamide
  参考文献：
  名称：

  Novel 3,4-Isoxazolediamides as Potent Inhibitors of Chaperone Heat Shock Protein 90

  摘要：

  A structural investigation on the isoxazole scaffold led to the discovery of 3,4-isoxazolediamide compounds endowed with potent Hsp90 inhibitory properties. We have found that compounds possessing a nitrogen atom directly attached to the C-4 heterocycle ring possess in vitro Hsp90 inhibitory properties at least comparable to those of the structurally related 4,S-diarylisoxazole derivatives. A group of compounds from this series of diamides combine potent binding affinity and cell growth inhibitory activity in both series of alkyl- and aryl- or heteroarylarnides, with IC50 in the low nanomolar range. The 3,4-isoxazolediamides were also very effective in causing dramatic depletion of the examined client proteins and, as expected for the Hsp90 inhibitors, always induced a very strong increase in the expression levels of the chaperone Hsp70. In vivo studies against human epidermoid carcinoma A431 showed an antitumor effect of morpholine derivative 73 comparable to that induced by the reference compound 10.

  DOI：

  10.1021/jm201155e
• 作为产物：
  描述：

  4-甲基-2-(4-吡啶基)噻唑-5-羧酸 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 4-Methyl-2-pyridin-4-yl-1,3-thiazole-5-carbonyl chloride
  参考文献：
  名称：

  作为 VEGFR-2/c-Met 双重抑制剂的 4-苯氧基-吡啶/嘧啶衍生物的设计、合成和生物学评价

  摘要：

  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

  DOI：

  10.1039/d2nj01561g

文献信息

• Novel 3,4-Isoxazolediamides as Potent Inhibitors of Chaperone Heat Shock Protein 90
  作者：Riccardo Baruchello、Daniele Simoni、Giuseppina Grisolia、Giuseppina Barbato、Paolo Marchetti、Riccardo Rondanin、Stefania Mangiola、Giuseppe Giannini、Tiziana Brunetti、Domenico Alloatti、Grazia Gallo、Andrea Ciacci、Loredana Vesci、Massimo Castorina、Ferdinando M. Milazzo、Maria L. Cervoni、Mario B. Guglielmi、Marcella Barbarino、Rosanna Foderà、Claudio Pisano、Walter Cabri

  DOI：10.1021/jm201155e

  日期：2011.12.22

  A structural investigation on the isoxazole scaffold led to the discovery of 3,4-isoxazolediamide compounds endowed with potent Hsp90 inhibitory properties. We have found that compounds possessing a nitrogen atom directly attached to the C-4 heterocycle ring possess in vitro Hsp90 inhibitory properties at least comparable to those of the structurally related 4,S-diarylisoxazole derivatives. A group of compounds from this series of diamides combine potent binding affinity and cell growth inhibitory activity in both series of alkyl- and aryl- or heteroarylarnides, with IC50 in the low nanomolar range. The 3,4-isoxazolediamides were also very effective in causing dramatic depletion of the examined client proteins and, as expected for the Hsp90 inhibitors, always induced a very strong increase in the expression levels of the chaperone Hsp70. In vivo studies against human epidermoid carcinoma A431 showed an antitumor effect of morpholine derivative 73 comparable to that induced by the reference compound 10.
• 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