ethyl 5-(1-ethoxycarbonyl-3-trifluoromethyl-1H-pyrazol-5-yl)thiophene-2-carboxylate | 223500-06-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 5-(1-ethoxycarbonyl-3-trifluoromethyl-1H-pyrazol-5-yl)thiophene-2-carboxylate
• 英文别名: ethyl 5-(5-ethoxycarbonylthiophen-2-yl)-3-(trifluoromethyl)pyrazole-1-carboxylate
• CAS: 223500-06-9
• 化学式: C₁₄H₁₃F₃N₂O₄S
• 分子量: 362.329
• InChiKey: RCUBWEZOOMCFCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  98.7
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 5-(1-ethoxycarbonyl-3-trifluoromethyl-1H-pyrazol-5-yl)thiophene-2-carboxylate 在 sodium hydroxide 、 水 、 碳酸氢钠 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 5-(1-ethyl-3-(trifluoromethyl)-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
• 作为产物：
  描述：

  2-噻吩甲酰三氟丙酮 在 正丁基锂 、 一水合肼 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 为溶剂， 反应 15.0h， 生成 ethyl 5-(1-ethoxycarbonyl-3-trifluoromethyl-1H-pyrazol-5-yl)thiophene-2-carboxylate
  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。
• Pyrazole derivative
  申请人：——

  公开号：US20010011090A1

  公开（公告）日：2001-08-02

  Drugs, in particular, pyrazole derivatives represented by the following general formula (I) which have a calcium release-dependent calcium channel inhibitory effect and medicinal compositions, in particular, calcium release-dependent calcium channel inhibitors containing the above compounds as the active ingredient, 1 (in the formula, each symbol has the following meaning: B: phenylene, a nitrogen-containing, divalent, saturated ring group, or a monocyclic, divalent heteroaromatic ring group which may be substituted with Alk, X: —NR 1 —CR 2 R 3 —, —CR 2 R 3 —NR 1 —, —NR 1 SO 2 —, —SO 2 —NR 1 — or —CR 4 ═CR 5 —, and A: benzene ring which may have one or more substituents; mono-, di- or tricyclic fused heteroaryl which may have one or more substituents; cycloalkyl which may have one or more substituents; a nitrogen-containing, saturated ring group which may have one or more substituents; lower alkenyl which may have one or more substituents; lower alkynyl which may have one or more substituents; or Alk which may have one or more substituents).

  药物，特别是由以下一般公式（I）代表的吡唑衍生物，具有依赖钙释放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依赖钙释放的钙通道抑制剂，1（在公式中，每个符号具有以下含义：B：苯基，含氮，二价，饱和环基，或带有Alk取代基的单环，二价杂芳环基；X：—NR1—CR2R3—，—CR2R3—NR1—，—NR1SO2—，—SO2—NR1—或—CR4═CR5—，和A：苯环，可能具有一个或多个取代基；单环、双环或三环融合的杂芳基，可能具有一个或多个取代基；可能具有一个或多个取代基的环烷基；可能具有一个或多个取代基的含氮饱和环基；可能具有一个或多个取代基的低烯基；可能具有一个或多个取代基的低炔基；或可能具有一个或多个取代基的Alk）。
• PYRAZOLE DERIVATIVES
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP1024138A1

  公开（公告）日：2000-08-02

  Drugs, in particular, pyrazole derivatives represented by the following general formula (I) which have a calcium release-dependent calcium channel inhibitory effect and medicinal compositions, in particular, calcium release-dependent calcium channel inhibitors containing the above compounds as the active ingredient, (in the formula, each symbol has the following meaning: D: pyrazolyl which may have 1 to 3 substituents selected from the group consisting of -Alk, -lower alkenyl, -lower alkynyl, -halogeno-lower alkyl, -Alk-cycloalkyl, -Alk-O-Alk, -cycloalkyl, -O-Alk, -COOH, -COO-Alk and -Hal, n: 0 or 1, B: phenylene, a nitrogen-containing, divalent, saturated ring group, or a monocyclic, divalent heteroaromatic ring group which may be substituted with Alk, X: -NR1-CR2R3-, -CR2R3-NR1-, -NR1-SO2-, -SO2-NR1- or -CR4=CR5-, and A: benzene ring which may have one or more substituents; mono-, di- or tricyclic fused heteroaryl which may have one or more substituents; cycloalkyl which may have one or more substituents; a nitrogen-containing, saturated ring group which may have one or more substituents; lower alkenyl which may have one or more substituents; lower alkynyl which may have one or more substituents; or Alk which may have one or more substituents).

  具有钙释放依赖性钙通道抑制作用的药物，特别是由以下通式(I)代表的吡唑衍生物，以及药物组合物，特别是含有上述化合物作为活性成分的钙释放依赖性钙通道抑制剂、 (式中各符号含义如下： D：吡唑基，可具有 1 至 3 个取代基，这些取代基选自由-Alk、-低级烯基、-低级炔基、-卤代低级烷基、-Alk-环烷基、-Alk-O-Alk、-环烷基、-O-Alk、-COOH、-COO-Alk 和-Hal 组成的组、 n:0或1、 B：亚苯基、含氮二价饱和环基或可被 Alk 取代的单环二价杂芳香环基、 X：-NR1-CR2R3-、-CR2R3-NR1-、-NR1-SO2-、-SO2-NR1-或-CR4=CR5-，以及 A：可具有一个或多个取代基的苯环；可具有一个或多个取代基的单环、二环或三环融合杂芳基；可具有一个或多个取代基的环烷基；可具有一个或多个取代基的含氮饱和环基；可具有一个或多个取代基的低级烯基；可具有一个或多个取代基的低级炔基；或可具有一个或多个取代基的烷基）。
• US6348480B1
  申请人：——

  公开号：US6348480B1

  公开（公告）日：2002-02-19
• US6958339B2
  申请人：——

  公开号：US6958339B2

  公开（公告）日：2005-10-25