3-(5-amino-3-t-butyl-pyrazol-1-yl)benzoic acid | 725685-93-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(5-amino-3-t-butyl-pyrazol-1-yl)benzoic acid
• 英文别名: 3-(3-tert-butyl-5-amino-1H-pyrazol-1-yl)benzoic acid；3-(5-amino-3-tert-butylpyrazol-1-yl)benzoic acid
• CAS: 725685-93-8
• 化学式: C₁₄H₁₇N₃O₂
• 分子量: 259.308
• InChiKey: LIUJJVCUIDFKSW-UHFFFAOYSA-N

物化性质

• 沸点：
  471.0±40.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  81.1
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  3-肼基苯甲酸 、 特戊酰氰 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 生成 3-(5-amino-3-t-butyl-pyrazol-1-yl)benzoic acid
  参考文献：
  名称：

  Biochemical and biophysical characterization of unique switch pocket inhibitors of p38α

  摘要：

  Herein we describe the identification and characterization of a class of molecules that are believed to extend into a region of p38 known as the 'switch pocket'. Although these molecules lack a canonical hinge binding motif, they show K(i) values as low as 100 nM against p38. We show that molecules that interact with this region of the protein demonstrate different binding kinetics than a canonical ATP mimetic, as well as a wide range of kinome profiles. Thus, the switch pocket presents new opportunities for kinome selectivity which could result in unique biochemical responses and offer new opportunities in the field of kinase drug discovery. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.04.097

文献信息

• Anti-inflammatory medicaments
  申请人：Flynn L. Daniel

  公开号：US20050288286A1

  公开（公告）日：2005-12-29

  Novel compounds and methods of using those compounds for the treatment of inflammatory conditions are provided. In a preferred embodiment, modulation of the activation state of p38 kinase protein comprises the step of contacting the kinase protein with the novel compounds.

  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激酶蛋白的活化状态包括将该激酶蛋白与新化合物接触的步骤。
• 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。
• 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。
• KINASE INHIBITORS USEFUL FOR THE TREATMENT OF MYLEOPROLIFIC DISEASES AND OTHER PROLIFERATIVE DISEASES
  申请人：Flynn Daniel L.

  公开号：US20080269267A1

  公开（公告）日：2008-10-30

  Compounds of the present invention find utility in the treatment of mammalian cancers and especially human cancers including but not limited to malignant melanomas, solid tumors, glioblastomas, ovarian cancer, pancreatic cancer, prostate cancer, lung cancers, breast cancers, kidney cancers, hepatic cancers, cervical carcinomas, metastasis of primary tumor sites, myeloproliferative diseases, chronic myelogenous leukemia, leukemias, papillary thyroid carcinoma, non-small cell lung cancer, mesothelioma, hypereosinophilic syndrome, gastrointestinal stromal tumors, colonic cancers, ocular diseases characterized by hyperproliferation leading to blindness including various retinopathies, diabetic retinopathy, rheumatoid arthritis, asthma, chronic obstructive pulmonary disease, mastocytosis, mast cell leukemia, a disease caused by c-Abl kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, a disease caused by c-Kit kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, a disease caused by c-Met kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof, or a disease caused by a Raf kinase, oncogenic forms thereof, aberrant fusion proteins thereof and polymorphs thereof.

  本发明的化合物可用于治疗哺乳动物癌症，特别是人类癌症，包括但不限于恶性黑色素瘤、实体肿瘤、胶质母细胞瘤、卵巢癌、胰腺癌、前列腺癌、肺癌、乳腺癌、肾癌、肝癌、宫颈癌、原发肿瘤部位的转移、骨髓增生性疾病、慢性髓细胞白血病、白血病、乳头状甲状腺癌、非小细胞肺癌、间皮瘤、高嗜酸性综合征、胃肠道间质瘤、结肠癌、眼部疾病，其特征是过度增殖导致失明，包括各种视网膜病变、糖尿病性视网膜病变、类风湿性关节炎、哮喘、慢性阻塞性肺疾病、肥大细胞增多症、肥大细胞白血病、由c-Abl激酶引起的疾病、其致癌形式、异常融合蛋白和多态体，由c-Kit激酶引起的疾病、其致癌形式、异常融合蛋白和多态体，由c-Met激酶引起的疾病、其致癌形式、异常融合蛋白和多态体，或由Raf激酶引起的疾病、其致癌形式、异常融合蛋白和多态体。
• 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。