1-{3-tert-butyl-1-(4-hydroxyphenyl)-1H-pyrazol-5-yl)-3-(4-chlorophenyl)urea | 725686-66-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-{3-tert-butyl-1-(4-hydroxyphenyl)-1H-pyrazol-5-yl)-3-(4-chlorophenyl)urea
• 英文别名: 1-(3-(Tert-butyl)-1-(4-hydroxyphenyl)-1H-pyrazol-5-yl)-3-(4-chlorophenyl)urea；1-[5-tert-butyl-2-(4-hydroxyphenyl)pyrazol-3-yl]-3-(4-chlorophenyl)urea
• CAS: 725686-66-8
• 化学式: C₂₀H₂₁ClN₄O₂
• 分子量: 384.865
• InChiKey: MRBWSSIJKYEYJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  79.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  1-(5-tert-butyl-2-(p-methoxy-phenyl)-2H-pyrazol-3-yl)-3-(4-chlorophenyl)urea 以62%的产率得到1-{3-tert-butyl-1-(4-hydroxyphenyl)-1H-pyrazol-5-yl)-3-(4-chlorophenyl)urea
  参考文献：
  名称：

  Anti-inflammatory medicaments

  摘要：

  提供了用于治疗炎症性疾病的新化合物和使用这些化合物的方法。在一个首选实施例中，调节p38激酶蛋白的激活状态包括将该激酶蛋白与新化合物接触的步骤。

  公开号：

  US07666895B2

文献信息

• MODULATION OF PROTEIN FUNCTIONALITIES
  申请人：Flynn Daniel L.

  公开号：US20080248548A1

  公开（公告）日：2008-10-09

  New methods for the rational identification of molecules capable of interacting with specific naturally occurring proteins are provided, in order to yield new pharmacologically important compounds and treatment modalities. Broadly, the method comprises the steps of identifying a switch control ligand forming a part of a particular protein of interest, and also identifying a complemental switch control pocket forming a part of the protein and which interacts with said switch control ligand. The ligand interacts in vivo with the pocket to regulate the conformation and biological activity of the protein such that the protein assumes a first conformation and a first biological activity upon the ligand-pocket interaction, and assumes a second, different conformation and biological activity in the absence of the ligand-pocket interaction. Next, respective samples of said protein in the first and second conformations are provided, and these are screened against one or more candidate molecules by contacting the molecules and the samples. Thereupon, small molecules which bind with the protein at the region of the pocket may be identified. Novel protein-modulator adducts and methods of altering protein activity are also provided.

  提供了一种新的方法，用于理性地识别能够与特定天然蛋白质相互作用的分子，以产生新的在药理学上重要的化合物和治疗方式。广义上，该方法包括以下步骤：识别构成感兴趣特定蛋白质一部分的开关控制配体，同时识别构成该蛋白质一部分并与该开关控制配体相互作用的互补开关控制口袋。该配体在体内与口袋相互作用，以调节蛋白质的构象和生物活性，使得蛋白质在配体-口袋相互作用时呈现第一构象和第一生物活性，并在缺乏配体-口袋相互作用时呈现第二不同构象和生物活性。接下来，提供了处于第一和第二构象的蛋白质的各自样本，并通过接触分子和样本对这些样本进行筛选。然后，可以识别与口袋区域的蛋白质结合的小分子。还提供了新颖的蛋白质调节剂加合物和改变蛋白质活性的方法。
• Modulation of protein functionalities
  申请人：——

  公开号：US20040171075A1

  公开（公告）日：2004-09-02

  New methods for the rational identification of molecules capable of interacting with specific naturally occurring proteins are provided, in order to yield new pharmacologically important compounds and treatment modalities. Broadly, the method comprises the steps of identifying a switch control ligand forming a part of a particular protein of interest, and also identifying a complemental switch control pocket forming a part of the protein and which interacts with said switch control ligand. The ligand interacts in vivo with the pocket to regulate the conformation and biological activity of the protein such that the protein assumes a first conformation and a first biological activity upon the ligand-pocket interaction, and assumes a second, different conformation and biological activity in the absence of the ligand-pocket interaction. Next, respective samples of said protein in the first and second conformations are provided, and these are screened against one or more candidate molecules by contacting the molecules and the samples. Thereupon, small molecules which bind with the protein at the region of the pocket may be identified. Novel protein-modulator adducts and methods of altering protein activity are also provided.

  提供了一种合理鉴定能够与特定自然存在的蛋白质相互作用的分子的新方法，以产生新的药理学重要化合物和治疗方法。广泛地说，该方法包括以下步骤：鉴定一个开关控制配体，其构成所需蛋白质的一部分，以及鉴定一个补充的开关控制口袋，其构成所需蛋白质的一部分，并与所述开关控制配体相互作用。配体在体内与口袋相互作用，以调节蛋白质的构象和生物活性，使蛋白质在配体-口袋相互作用时呈现第一构象和第一生物活性，并在缺乏配体-口袋相互作用时呈现第二种不同的构象和生物活性。接下来，提供所述蛋白质的第一和第二构象的各个样品，并通过接触分子和样品筛选一个或多个候选分子。然后，可以鉴定与口袋区域的蛋白质结合的小分子。还提供了新的蛋白质调节剂加合物和改变蛋白质活性的方法。
• Enzyme modulators and treatments
  申请人：Flynn L. Daniel

  公开号：US20070078121A1

  公开（公告）日：2007-04-05

  Novel compounds and methods of using those compounds for the treatment of inflammatory conditions, immunological disorders, hyperproliferative diseases, cancer, and diseases characterized by hyper-vascularization are provided. In a preferred embodiment, modulation of the activation state of kinases, including p38 kinase protein, abl kinase protein, bcr-abl kinase protein, braf kinase protein, VEGFR kinase protein, or PDGFR kinase protein, comprises the step of contacting said kinase protein with the novel compounds.

  提供了新型化合物及其使用方法，用于治疗炎症性疾病、免疫性疾病、过度增生性疾病、癌症以及以高血管化为特征的疾病。在一种优选实施方式中，调节激酶的激活状态，包括p38激酶蛋白、abl激酶蛋白、bcr-abl激酶蛋白、braf激酶蛋白、VEGFR激酶蛋白或PDGFR激酶蛋白，包括将该激酶蛋白与新型化合物接触的步骤。
• ENZYME MODULATORS AND TREATMENTS
  申请人：Flynn L. Daniel

  公开号：US20080113967A1

  公开（公告）日：2008-05-15

  Novel compounds and methods of using those compounds for the treatment of inflammatory conditions, hyperproliferative diseases, cancer, and diseases characterized by hyper-vascularization are provided. In a preferred embodiment, modulation of the activation state of p38 kinase protein, abl kinase protein, ber-abl kinase protein, braf kinase protein, VEGFR kinase protein, or PDGFR kinase protein comprises the step of contacting said kinase protein with the novel compounds.

  本发明提供了新的化合物及其使用方法，用于治疗炎症状况、过度增殖性疾病、癌症和以高血管化为特征的疾病。在优选实施例中，调节p38激酶蛋白、abl激酶蛋白、ber-abl激酶蛋白、braf激酶蛋白、VEGFR激酶蛋白或PDGFR激酶蛋白的激活状态，包括将该激酶蛋白与新的化合物接触的步骤。
• ANTI-INFLAMMATORY MEDICAMENTS
  申请人：Flynn Daniel L.

  公开号：US20090312349A1

  公开（公告）日：2009-12-17

  Novel compounds and methods of using those compounds for the treatment of inflammatory conditions, hyperproliferative diseases, cancer, and diseases characterized by hyper-vascularization are provided. In a preferred embodiment, modulation of the activation state of p38 kinase protein, abl kinase protein, bcr-abl kinase protein, braf kinase protein, VEGFR kinase protein, or PDGFR kinase protein comprises the step of contacting said kinase protein with the novel compounds.

  本发明提供了新型化合物及其使用方法，用于治疗炎症状况、过度增殖性疾病、癌症和以高血管化为特征的疾病。在一个优选实施例中，调节p38激酶蛋白、abl激酶蛋白、bcr-abl激酶蛋白、braf激酶蛋白、VEGFR激酶蛋白或PDGFR激酶蛋白的活化状态包括将该激酶蛋白与新型化合物接触的步骤。