5-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxylic acid | 656226-60-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: 5-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxylic acid
• 英文别名: 5-(2-methylpyrazol-3-yl)thiophene-2-carboxylic acid
• CAS: 656226-60-7
• 化学式: C₉H₈N₂O₂S
• 分子量: 208.241
• InChiKey: AYJZFZLMYCKKMS-UHFFFAOYSA-N

物化性质

• 沸点：
  423.3±35.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  83.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxylic acid 在 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 、 肼 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 34.0h， 生成 (S)-N-(2-amino-1-{[2-(trifluoromethyl)phenyl]methyl}ethyl)-5-(1-methyl-1H-pyrazol-5-yl)-2-thiophenecarboxamide
  参考文献：
  名称：

  WO2008/98104

  摘要：

  公开号：
• 作为产物：
  描述：

  ethyl 5-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxylate 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 19.0h， 以64%的产率得到5-(1-methyl-1H-pyrazol-5-yl)thiophene-2-carboxylic acid
  参考文献：
  名称：

  Novel potent and selective calcium-release-activated calcium (CRAC) channel inhibitors. Part 2: Synthesis and inhibitory activity of aryl-3-trifluoromethylpyrazoles

  摘要：

  To identify potent and selective calcium-release-activated calcium (CRAG) channel inhibitors, we examined the structure-activity relationships of the pyrazole and thiophene moieties in compound 4. Compound 25b was found to exhibit highly potent and selective inhibitory activity for CRAC channels and further modifications of the pyrazole and benzoyl moieties of compound 25b produced compound 29. These compounds were potent inhibitors of IL-2 production in vitro and also acted as inhibitors in pharmacological models of diseases resulting from T-lymphocyte activation, after oral administration. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.03.039

文献信息

• Pharmaceutical compound comprising a pyrazole derivative and methods of using the same for the treatment of calcium release-activated calcium channel associated diseases
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US06348480B1

  公开（公告）日：2002-02-19

  The present invention is directed to drugs, in particular, pyrazole derivatives represented by the following general formula (I) which have a calcium release-activated calcium channel inhibitory effect and medicinal compositions, in particular, calcium release-activated calcium channel inhibitors containing the above compounds as the active ingredient, wherein each substituent is defined in the specification. The present invention also relates to a pharmaceutical composition containiing an effective amount of the compound of formula (I) and a pharmaceutically effective carrier. The present invention further relates to methods of treatment of diseases associated with calcium release-activated calcium channels, diseases associated with IL-2 production, and methods of treatment of allergic, inflammatory or auto-immune diseases.

  本发明涉及药物，特别是由以下一般式（I）表示的吡唑衍生物，其具有钙释放激活的钙通道抑制作用和药用组合物，特别是含有上述化合物作为活性成分的钙释放激活的钙通道抑制剂，其中每个取代基在规范中定义。本发明还涉及含有一定量的式（I）化合物和药效载体的药用组合物。本发明还涉及与钙释放激活的钙通道相关的疾病、与IL-2产生相关的疾病以及过敏、炎症或自身免疫疾病的治疗方法。
• [EN] SUBSTITUTED THIENYL-HYDROXAMIC ACIDS AS HISTONE DEACETYLASE INHIBITORS<br/>[FR] ACIDES SUBSTITUES THIENYLHYDROXAMIQUES UTILISES EN TANT QU'INHIBITEURS D'HISTONE DESACETYLASE
  申请人：ARGENTA DISCOVERY LTD

  公开号：WO2004013130A1

  公开（公告）日：2004-02-12

  A compound of formula (I): which can be used in the treatment of diseases associated with histone deacetylase enzymatic activity.

  化合物的化学式（I）：可用于治疗与组蛋白去乙酰化酶活性相关的疾病。
• Discovery of pyrazole-thiophene derivatives as highly Potent, orally active Akt inhibitors
  作者：Wenhu Zhan、Jinxin Che、Lei Xu、Yizhe Wu、Xiaobei Hu、Yubo Zhou、Gang Cheng、Yongzhou Hu、Xiaowu Dong、Jia Li

  DOI：10.1016/j.ejmech.2019.07.017

  日期：2019.10

  A series of pyrazole-thiophene derivatives exhibiting good Akt inhibitory activities were obtained on the basis of conformational restriction strategy, leading to the discovery of compound 1d and 1o which showed excellent in vitro antitumor effect against a variety of hematologic cancer cells and their potential of inducing apoptosis, blocking the cell cycles at S phase and significantly inhibiting

  在构象限制策略的基础上，获得了一系列表现出良好的Akt抑制活性的吡唑-噻吩衍生物，从而发现了化合物1d和1o对多种血液癌细胞具有优异的体外抗肿瘤作用及其诱导潜力。凋亡，阻断S期的细胞周期，并显着抑制癌细胞Akt激酶下游生物标记的磷酸化。其中，化合物1o在MM1S异种移植模型中也表现出良好的PK特性，并抑制了约40％的肿瘤生长。化合物1o可能是进一步开发的潜在候选者。
• Inhibitors of AKT Activity
  申请人：Novartis AG

  公开号：US20160287561A1

  公开（公告）日：2016-10-06

  Invented are novel heterocyclic carboxamide compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.

  本发明涉及一种新型杂环羧酰胺化合物，其作为蛋白激酶B活性的抑制剂以及在癌症和关节炎治疗中的应用。
• INHIBITORS OF Akt ACTIVITY
  申请人：Seefeld Mark A.

  公开号：US20100041726A1

  公开（公告）日：2010-02-18

  Invented are novel heterocyclic carboxamide compounds, the use of such compounds as inhibitors of protein kinase B activity and in the treatment of cancer and arthritis.

  本发明提供了一种新型杂环羧酰胺化合物，该化合物可用作蛋白激酶B活性的抑制剂，并可用于治疗癌症和关节炎。