ethyl 2-(4-chloro-3-nitrophenyl)-4-methylthiazole-5-carboxylate | 144060-69-5

• 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: ethyl 2-(4-chloro-3-nitrophenyl)-4-methylthiazole-5-carboxylate
• 英文别名: ethyl 2-(4-chloro-3-nitrophenyl)-4-methyl-5-thiazolecarboxylate；ethyl 2-(4-chloro-3-nitrophenyl)-4-methyl-1,3-thiazole-5-carboxylate
• CAS: 144060-69-5
• 化学式: C₁₃H₁₁ClN₂O₄S
• 分子量: 326.76
• InChiKey: QLRKACSNVXVLNL-UHFFFAOYSA-N

物化性质

• 沸点：
  462.3±55.0 °C(predicted)
• 密度：
  1.409±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  113
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-(4-chloro-3-nitrophenyl)-4-methylthiazole-5-carboxylate 在 2-(4-N,N-diethylamino)-3-nitrophenyl 作用下， 以 二乙胺 为溶剂， 以hydrolyzed to give 2-(4-N,N-diethylamino)-3-nitrophenyl)-4-methyl-5-thiazolecarboxylic acid (yield: 56%)的产率得到4-甲基噻唑-5-甲酸
  参考文献：
  名称：

  2-arylthiazole derivatives and pharmaceutical composition thereof

  摘要：

  本发明提供了用于治疗痛风或高尿酸血症的药物组合物，其含有一种新的分类化合物2-芳基噻唑衍生物作为活性成分。本发明中的2-芳基噻唑衍生物由以下式子（I）表示： 其中，Ar是未取代或取代的吡啶基，噻吩基，呋喃基，萘基或苯基；X是氢原子，烷基或可保护的羧基；Y是氢原子，烷基，或可保护的羟基或羰基。此外，本发明还提供了包括在2-芳基噻唑衍生物中的新化合物及其药学上可接受的盐。

  公开号：

  US05614520A1
• 作为产物：
  描述：

  4-氯-3-硝基苯甲腈 在 劳森试剂 、 双氧水 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 ethyl 2-(4-chloro-3-nitrophenyl)-4-methylthiazole-5-carboxylate
  参考文献：
  名称：

  Synthesis and Evaluation of Sulfonylnitrophenylthiazoles (SNPTs) as Thyroid Hormone Receptor–Coactivator Interaction Inhibitors

  摘要：

  We previously identified a series of methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its coactivators. MSNBs inhibit coactivator binding through irreversible modification of cysteine 298 of the thyroid hormone receptor (TR). Although MSNBs have better pharmacological features than our first generation inhibitors (beta-aminoketones), they contain a potentially unstable ester linkage. Here we report the bioisosteric replacement of the ester linkage with a thiazole moiety, yielding sulfonylnitrophenylthiazoles (SNPTs). An array of SNPTs representing optimal side chains from the MSNB series was constructed using parallel chemistry and evaluated to test their antagonism of the TR-coactivator interaction. Selected active compounds were evaluated in secondary confirmatory assays including regulation of thyroid response element driven transcription in reporter constructs and native genes. In addition the selected SNPTs were shown to be selective for TR relative to other nuclear hormone receptors (NRs).

  DOI：

  10.1021/jm201546m

文献信息

• 2-ARYLTHIAZOLE DERIVATIVE AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME
  申请人：TEIJIN LIMITED

  公开号：EP0513379B1

  公开（公告）日：1996-09-11
• US5614520A
  申请人：——

  公开号：US5614520A

  公开（公告）日：1997-03-25
• 2-arylthiazole derivatives and pharmaceutical composition thereof
  申请人：Teijin Limited

  公开号：US05614520A1

  公开（公告）日：1997-03-25

  Pharmaceutical compositions for treating gout or hyperuricemia and containing a new categorized compound, i.e. 2-arylthiazole derivatives, as an active ingredient, are provided. The 2-arylthiazole derivatives in the present invention are represented by the following formula (I): ##STR1## wherein Ar is an unsubstituted or substituted pyridyl, thienyl, furyl, naphthyl or phenyl group; X is a hydrogen atom, alkyl group or carboxyl group which may be protected, and Y is a hydrogen atom, alkyl group, or a hydroxyl or carbonyl group which may be protected. Furthermore, novel compounds included in the 2-arylthiazole derivatives and pharmaceutically acceptable salts thereof are provided.

  提供用于治疗痛风或高尿酸血症的药物组合物，含有一种新分类化合物，即2-芳基噻唑衍生物，作为活性成分。本发明中的2-芳基噻唑衍生物由以下式（I）表示：其中Ar是未取代或取代的吡啶基、噻吩基、呋喃基、萘基或苯基；X是氢原子、烷基或可保护的羧基，Y是氢原子、烷基或可保护的羟基或羰基。此外，提供了包括在2-芳基噻唑衍生物中的新化合物及其药用盐。
• Synthesis and Evaluation of Sulfonylnitrophenylthiazoles (SNPTs) as Thyroid Hormone Receptor–Coactivator Interaction Inhibitors
  作者：Jong Yeon Hwang、Ramy R. Attia、Fangyi Zhu、Lei Yang、Andrew Lemoff、Cynthia Jeffries、Michele C. Connelly、R. Kiplin Guy

  DOI：10.1021/jm201546m

  日期：2012.3.8

  We previously identified a series of methylsulfonylnitrobenzoates (MSNBs) that block the interaction of the thyroid hormone receptor with its coactivators. MSNBs inhibit coactivator binding through irreversible modification of cysteine 298 of the thyroid hormone receptor (TR). Although MSNBs have better pharmacological features than our first generation inhibitors (beta-aminoketones), they contain a potentially unstable ester linkage. Here we report the bioisosteric replacement of the ester linkage with a thiazole moiety, yielding sulfonylnitrophenylthiazoles (SNPTs). An array of SNPTs representing optimal side chains from the MSNB series was constructed using parallel chemistry and evaluated to test their antagonism of the TR-coactivator interaction. Selected active compounds were evaluated in secondary confirmatory assays including regulation of thyroid response element driven transcription in reporter constructs and native genes. In addition the selected SNPTs were shown to be selective for TR relative to other nuclear hormone receptors (NRs).