N²-(4-ethoxyphenyl)benzo[d]oxazole-2,5-diamine | 1361414-87-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶唑类
• 英文名称: N²-(4-ethoxyphenyl)benzo[d]oxazole-2,5-diamine
• 英文别名: 2-N-(4-ethoxyphenyl)-1,3-benzoxazole-2,5-diamine
• CAS: 1361414-87-0
• 化学式: C₁₅H₁₅N₃O₂
• 分子量: 269.303
• InChiKey: NDDYSUWOYSZECO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  73.3
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  N²-(4-ethoxyphenyl)benzo[d]oxazole-2,5-diamine 、 乙基磺酰氯 在 三乙胺 作用下， 生成 N-[2-(4-ethoxyanilino)-1,3-benzoxazol-5-yl]ethanesulfonamide
  参考文献：
  名称：

  Hit to lead SAR study on benzoxazole derivatives for an NPY Y5 antagonist

  摘要：

  We report a hit to lead study on a novel benzoxazole NPY Y5 antagonist. Starting from HTS hit 1, structure-activity relationships were developed. Compound 12 showed reduction of food intake and a tendency to suppress body weight gain over the 21-day experimental period. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.027
• 作为产物：
  描述：

  2-巯基-5-硝基苯并噁唑 在 氯化亚砜 、 palladium on activated charcoal 、 氢气 作用下， 生成 N²-(4-ethoxyphenyl)benzo[d]oxazole-2,5-diamine
  参考文献：
  名称：

  Hit to lead SAR study on benzoxazole derivatives for an NPY Y5 antagonist

  摘要：

  We report a hit to lead study on a novel benzoxazole NPY Y5 antagonist. Starting from HTS hit 1, structure-activity relationships were developed. Compound 12 showed reduction of food intake and a tendency to suppress body weight gain over the 21-day experimental period. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.01.027

文献信息

• Novel Small Molecule Inhibitors Targeting the IL-6/STAT3 Pathway or IL-1β
  作者：Jihye Yoo、Darong Kim、Jiyoung Park、Young-Kook Kim、Hea-Young Park Choo、Hyun Ae Woo

  DOI：10.3390/molecules27092696

  日期：——

  Development of small molecules that inhibit inflammatory cytokines is a desirable strategy for the treatment of inflammatory diseases such as rheumatoid arthritis (RA). Following up a previous study, we synthesized 10 novel compounds with a 2,5-diaminobenzoxazole moiety and evaluated their biological activities. Among them, compound 3e showed potent inhibitory activity on Interleukin 6 (IL-6)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling inhibition (71.5%), and 3a showed excellent inhibitory activity on Interleukin 1 (IL-1β) (92.1%). To test in vivo anti-inflammatory activity, compounds 3a and 3e were administered by intraperitoneal (IP) injection after subcutaneous (SC) injection of zymosan A into the right footpad of mice. Inflammation on the footpad was reduced after administration of compounds 3a and 3e. Especially, compound 3a showed a significant ameliorative effect on zymosan-induced inflammation. From the in vivo and in vitro test results, we confirmed that our synthesized compounds are effective on the RA animal model through inhibition of the IL-6/STAT3 signaling pathway. Since drugs developed with small molecule inhibitors have several advantages over biological drugs, further study on these compounds is needed for the development of potent SMI drugs on RA.

  开发能够抑制炎性细胞因子的小分子化合物是治疗类风湿性关节炎等炎性疾病的理想策略。在之前的研究基础上，我们合成了10个新的化合物，其中含有2,5-二氨基苯并咪唑基团，并评估了它们的生物活性。其中，化合物3e在白细胞介素6（IL-6）/信号转导和转录激活子3（STAT3）信号抑制方面表现出强烈的抑制活性（71.5％），而3a在白细胞介素1（IL-1β）方面表现出优异的抑制活性（92.1％）。为了测试体内的抗炎活性，将化合物3a和3e通过腹腔注射给小鼠，然后在小鼠的右脚趾下皮下注射半乳糖神经酰胺A。化合物3a和3e的给药后，足底的炎症得到了减轻。特别是，化合物3a对半乳糖神经酰胺A诱导的炎症具有显著的改善作用。通过体内和体外实验结果，我们确认我们合成的化合物通过抑制IL-6 / STAT3信号通路对类风湿性关节炎动物模型具有有效性。由于使用小分子抑制剂开发的药物具有多种优势，因此需要进一步研究这些化合物，以开发出对类风湿性关节炎具有强效作用的小分子抑制剂药物。
• Hit to lead SAR study on benzoxazole derivatives for an NPY Y5 antagonist
  作者：Naoki Omori、Naoki Kouyama、Akira Yukimasa、Kana Watanabe、Yasunori Yokota、Hideki Tanioka、Hirohide Nambu、Hideo Yukioka、Norihito Sato、Yukari Tanaka、Kazutaka Sekiguchi、Takayuki Okuno

  DOI：10.1016/j.bmcl.2012.01.027

  日期：2012.3

  We report a hit to lead study on a novel benzoxazole NPY Y5 antagonist. Starting from HTS hit 1, structure-activity relationships were developed. Compound 12 showed reduction of food intake and a tendency to suppress body weight gain over the 21-day experimental period. (C) 2012 Elsevier Ltd. All rights reserved.