1-(4-nitrophenyl)-4-(trifluoromethyl)-1H-pyrazole | 1393125-56-8

• 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-(4-nitrophenyl)-4-(trifluoromethyl)-1H-pyrazole
• 英文别名: 1-(4-nitrophenyl)-4-(trifluoromethyl)pyrazole
• CAS: 1393125-56-8
• 化学式: C₁₀H₆F₃N₃O₂
• 分子量: 257.172
• InChiKey: UYTHUHCQEWRQLK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  63.6
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(4-nitrophenyl)-4-(trifluoromethyl)-1H-pyrazole 在 癸硼烷 、 palladium 10% on activated carbon 、 水 、 甲酸铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 为溶剂， 生成 ethyl 3-(4-(1-(4-(4-(trifluoromethyl)-1H-pyrazol-1-yl)phenylamino)butyl)benzamido)propanoate
  参考文献：
  名称：

  The design and synthesis of a potent glucagon receptor antagonist with favorable physicochemical and pharmacokinetic properties as a candidate for the treatment of type 2 diabetes mellitus

  摘要：

  A novel and potent small molecule glucagon receptor antagonist for the treatment of diabetes mellitus is reported. This candidate, (S)-3-[4-(1-{3,5-dimethyl-4-[4-(trifluoromethyl)-1H-pyrazol-1-yl]phenoxy}butyl)benzamido]propanoic acid, has lower molecular weight and lipophilicity than historical glucagon receptor antagonists, resulting in excellent selectivity in broad-panel screening, lower cytotoxicity, and excellent overall in vivo safety in early pre-clinical testing. Additionally, it displays low in vivo clearance and excellent oral bioavailability in both rats and dogs. In a rat glucagon challenge model, it was shown to reduce the glucagon-elicited glucose excursion in a dose-dependent manner and at a concentration consistent with its rat in vitro potency. Its properties make it an excellent candidate for further investigation. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.014
• 作为产物：
  描述：

  对氟硝基苯 、 4-(三氟甲基)-1H-吡唑 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 以70%的产率得到1-(4-nitrophenyl)-4-(trifluoromethyl)-1H-pyrazole
  参考文献：
  名称：

  The design and synthesis of a potent glucagon receptor antagonist with favorable physicochemical and pharmacokinetic properties as a candidate for the treatment of type 2 diabetes mellitus

  摘要：

  A novel and potent small molecule glucagon receptor antagonist for the treatment of diabetes mellitus is reported. This candidate, (S)-3-[4-(1-{3,5-dimethyl-4-[4-(trifluoromethyl)-1H-pyrazol-1-yl]phenoxy}butyl)benzamido]propanoic acid, has lower molecular weight and lipophilicity than historical glucagon receptor antagonists, resulting in excellent selectivity in broad-panel screening, lower cytotoxicity, and excellent overall in vivo safety in early pre-clinical testing. Additionally, it displays low in vivo clearance and excellent oral bioavailability in both rats and dogs. In a rat glucagon challenge model, it was shown to reduce the glucagon-elicited glucose excursion in a dose-dependent manner and at a concentration consistent with its rat in vitro potency. Its properties make it an excellent candidate for further investigation. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.014

文献信息

• GLUCAGON RECEPTOR MODULATORS
  申请人：Aspnes Gary Erik

  公开号：US20120202834A1

  公开（公告）日：2012-08-09

  The present invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof wherein R 1 , R 2 , R 3 , A 1 , A 2 , A 3 , A 4 , L, B 1 , B 2 , B 3 and B 4 are as defined herein. The compounds of Formula I have been found to act as glucagon antagonists or inverse agonists. Consequently, the compounds of Formula I and the pharmaceutical compositions thereof are useful for the treatment of diseases, disorders, or conditions mediated by glucagon.

  本发明提供了一种式（I）的化合物或其药学上可接受的盐，其中R1、R2、R3、A1、A2、A3、A4、L、B1、B2、B3和B4如本文所定义。已发现式I的化合物可作为葡萄糖胰高血糖素拮抗剂或逆向激动剂。因此，式I的化合物及其药物组成物对于治疗由葡萄糖胰高血糖素介导的疾病、紊乱或症状是有用的。
• Glucagon receptor modulators
  申请人：Pfizer Inc.

  公开号：US08859591B2

  公开（公告）日：2014-10-14

  The present invention provides a compound of Formula (I) or a pharmaceutically acceptable salt thereof wherein R1, R2, R3, A1, A2, A3, A4, L, B1, B2, B3 and B4 are as defined herein. The compounds of Formula I have been found to act as glucagon antagonists or inverse agonists. Consequently, the compounds of Formula I and the pharmaceutical compositions thereof are useful for the treatment of diseases, disorders, or conditions mediated by glucagon.

  本发明提供了公式（I）的化合物或其药学上可接受的盐，其中R1、R2、R3、A1、A2、A3、A4、L、B1、B2、B3和B4的定义如本文所述。发现公式I的化合物可作为胰高血糖素拮抗剂或反向激动剂。因此，公式I的化合物及其药物组合物对于治疗由胰高血糖素介导的疾病、疾病或病况是有用的。
• Compounds and their use for reducing uric acid levels
  申请人：Acquist LLC

  公开号：US10752613B2

  公开（公告）日：2020-08-25

  Bifunctional compounds that increase uric acid excretion and reduce uric acid production, and monofunctional compounds that either increase uric acid excretion or reduce uric acid production. Methods of using these compounds for reducing uric acid levels in blood or serum, for treating disorders of uric acid metabolism, and for maintaining normal uric acid levels in blood or serum are also provided. Pharmaceutical compositions comprising the bifunctional and monofunctional compounds are also provided.

  提供了可增加尿酸排泄和减少尿酸生成的双官能化合物，以及可增加尿酸排泄或减少尿酸生成的单官能化合物。还提供了使用这些化合物降低血液或血清中尿酸水平、治疗尿酸代谢紊乱以及维持血液或血清中正常尿酸水平的方法。还提供了包含双官能和单官能化合物的药物组合物。
• [EN] AMIDE DERIVATIVES, PREPARATION PROCESS THEREOF AND USE THEREOF IN MEDICINE<br/>[FR] DÉRIVÉS D'AMIDE, LEUR PROCÉDÉ DE PRÉPARATION ET LEUR UTILISATION EN MÉDECINE<br/>[ZH] 酰胺类衍生物、其制备方法及其在医药上的用途
  申请人：ZHEJIANG HISUN PHARM CO LTD

  公开号：WO2017215586A1

  公开（公告）日：2017-12-21

  提供酰胺类衍生物、其制备方法及其在医药上的应用。具体而言，提供一种通式（I）所示的酰胺类衍生物或其可药用的盐、其制备方法，以及它们作为治疗剂，特别是作为胰高血糖受体拮抗剂的用途。
• GLUCAGON RECEPTOR MODULATOR
  申请人：Pfizer Inc.

  公开号：EP2673260B1

  公开（公告）日：2016-08-17