1-[3-氰基-4-(2,2-二甲基丙氧基)苯基]-1H-吡唑-4-羧酸 | 206884-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-[3-氰基-4-(2,2-二甲基丙氧基)苯基]-1H-吡唑-4-羧酸
• 英文名称: [14C]-Piraxostat
• 英文别名: 1-[3-cyano-4-(2,2-dimethylpropoxy)phenyl]-1H-pyrazole-4-carboxylic acid；1-(3'-cyano-4'-neopentyloxyphenyl)-pyrazol-4-carboxylic acid；1-(3-cyano-4-neopentyloxyphenyl)pyrazole-4-carboxylic acid；Y-700；1-(3-cyano-4-(2,2-dimethylpropoxy)phenyl)-1H-pyrazole-4-carboxylic acid；Niraxostat；1-[3-cyano-4-(2,2-dimethylpropoxy)phenyl]pyrazole-4-carboxylic acid
• CAS: 206884-98-2
• 化学式: C₁₆H₁₇N₃O₃
• 分子量: 299.329
• InChiKey: AETHRPHBGJAIBT-UHFFFAOYSA-N

物化性质

• 沸点：
  500.5±45.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  88.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  ethyl 1-(3'-cyano-4'-neopentyloxyphenyl)-pyrazol-4-carboxylate 在 水 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 以55%的产率得到1-[3-氰基-4-(2,2-二甲基丙氧基)苯基]-1H-吡唑-4-羧酸
  参考文献：
  名称：

  强力黄嘌呤氧化还原酶抑制剂1-苯基-吡唑-4-羧酸衍生物的合成及生物评价

  摘要：

  合成了多种多样的1-苯基-吡唑-4-羧酸衍生物库，并对其在体外和体内对黄嘌呤氧化还原酶（XOR）的抑制能力进行了评估，并进行了结构-活性关系（SAR）分析。大约一半的目标化合物在纳摩尔水平上表现出对XOR的抑制能力。与非布索坦相比，化合物16c，16d和16f成为最有效的黄嘌呤氧化还原酶抑制剂，IC 50值分别为5.7、5.7和4.2 nM（IC 50为5.4 nM）。稳态动力学测量表明16c是一种混合型抑制剂。进行了与XOR结合的16c的计算机分子对接研究，以深入了解其与该系列的结合模式和SAR。选择了由草酸钾-次黄嘌呤诱导的小鼠高尿酸血症模型，以进一步证实16c和16f的降尿酸作用，结果表明16c表现出与非布索坦相似的降尿酸功效。

  DOI：

  10.1016/j.ejmech.2017.08.047

文献信息

• 1-phenylpyrazole compounds and medicinal application thereof
  申请人：Yoshitomi Pharmaceutical Industries, ltd.

  公开号：US06015829A1

  公开（公告）日：2000-01-18

  1-Phenylpyrazole compounds of the formula (1): ##STR1## which is exemplified by 5-amino-1-(3-cyano-4-isobutoxyphenyl)pyrazole-4-carboxylic acid, an optical isomer thereof and a pharmaceutically acceptable salt thereof. These compounds have a xanthine oxidase inhibitory activity and are useful as therapeutic agents for diseases such as hyperuricacidemia and gout.

  公式（1）的1-苯基吡唑化合物：##STR1##例如5-氨基-1-(3-氰基-4-异丁氧基苯基)吡唑-4-羧酸及其光学异构体和药学上可接受的盐。这些化合物具有黄嘌呤氧化酶抑制活性，并且可用作治疗高尿酸血症和痛风等疾病的治疗剂。
• AGENT FOR TREATING OR PREVENTING DIGESTIVE ULCER
  申请人：Kawakami Masakatsu

  公开号：US20090036428A1

  公开（公告）日：2009-02-05

  An object of the present invention is to provide an agent for treating or preventing digestive ulcer that is effective even to ulcer of small intestine and others, for which gastric acid secretion inhibitors such as proton pump inhibitors are ineffective, and is superior to allopurinol in the efficaciousness and the safety. The pharmaceutical composition of the present invention comprising a non-purine xanthine oxidase inhibitor as the active ingredient is useful as an agent for treating or preventing ulcer that forms in digestive tracts by the attack of gastric acid, pepsin, stress, Helicobacter pylori bacteria, NSAID, etc. In particular, it is useful as an ulcer remedy heretofore unknown in the art as it is effective even for ulcer in small intestine for which gastric/duodenal ulcer remedies that inhibit gastric acid secretion such as proton pump inhibitors are ineffective.

  本发明的目的是提供一种治疗或预防消化性溃疡的药剂，即使是质子泵抑制剂对小肠溃疡等无效的溃疡也能有效治疗或预防，并且在功效和安全性方面优于丙戊酸和乙酰水杨酸等药物。本发明的药物组合物包括非嘌呤黄嘌呤氧化酶抑制剂作为活性成分，可用作治疗或预防由胃酸、胃蛋白酶、压力、幽门螺杆菌、NSAID等侵蚀消化道形成的溃疡的药剂。特别是，它是一种迄今为止在技术上未知的溃疡治疗方法，因为它即使对于质子泵抑制剂等抑制胃酸分泌的胃/十二指肠溃疡治疗方法也非常有效，对于小肠溃疡也非常有效。
• Xanthine Oxidase Inhibitor
  申请人：Yoshida Shinichi

  公开号：US20070265283A1

  公开（公告）日：2007-11-15

  The invention relates to compounds of the following formula (I) or their salts: in which R 1 represents OR 4 or others, in which R 4 is an alkyl group having 1-8 carbon atoms which may have a substituent or the like; R 2 is halogen, nitro, cyano, carboxyl, or the like; R 3 is hydrogen, halogen, hydroxyl, amino, carboxyl, or the like; X is NR 11 , oxygen, or sulfur, in which R 11 is hydrogen, or an alkyl group having 1-8 carbon atom which may have a substituent; and each of Y and Z is CR 12 or nitrogen, in which R 12 has the same meaning as R 3 above, and a xanthine oxidase inhibitor containing the compound as an active ingredient.

  本发明涉及以下公式（I）的化合物或其盐： 其中，R1代表OR4或其他，其中R4是1-8个碳原子的烷基基团，可以具有取代基或类似物；R2是卤素，硝基，氰基，羧基或类似物；R3是氢，卤素，羟基，氨基，羧基或类似物；X是NR11，氧或硫，其中R11是氢或1-8个碳原子的烷基基团，可以具有取代基；每个Y和Z都是CR12或氮，其中R12具有与上述R3相同的含义；以及一种以该化合物为活性成分的黄嘌呤氧化酶抑制剂。
• Condensed Pyrimidine Deriviative and Xanthine Oxidase Inhibitor
  申请人：Yoshida Shinichi

  公开号：US20070293512A1

  公开（公告）日：2007-12-20

  The invention relates to compounds of the following formula (I) or their salts: in which R 1 is a group of phenyl, naphthyl, pyridyl or the like which may have a substituent such as an alkyl group having 1-8 carbon atoms, an alkoxy group having 1-8 carbon atoms, an alkoxycarbonyl group having 2-8 carbon atoms, carboxyl, halogen, hydroxyl, nitro, or cyano; R 2 is cyano, nitro, or the like; R 3 is hydroxyl or the like; X is oxygen, sulfur, or the like; and Y is oxygen or sulfur, and a xanthine oxidase inhibitor containing the compound.

  本发明涉及以下式（I）或其盐的化合物： 其中，R1是苯基、萘基、吡啶基或类似基团，该基团可以具有取代基，例如具有1-8个碳原子的烷基基团、具有1-8个碳原子的烷氧基团、具有2-8个碳原子的烷氧羰基团、羧基、卤素、羟基、硝基或氰基；R2是氰基、硝基或类似基团；R3是羟基或类似基团；X是氧、硫或类似物；Y是氧或硫。本发明还涉及含有该化合物的黄嘌呤氧化酶抑制剂。
• 1-PHENYLPYRAZOLE COMPOUNDS AND MEDICINAL APPLICATION THEREOF
  申请人：YOSHITOMI PHARMACEUTICAL INDUSTRIES, LTD.

  公开号：EP0936217A1

  公开（公告）日：1999-08-18

  1-Phenylpyrazole compounds of the formula (1): which is exemplified by 5-amino-1-(3-cyano-4-isobutoxyphenyl)pyrazole-4-carboxylic acid, an optical isomer thereof and a pharmaceutically acceptable salt thereof. These compounds have a xanthine oxidase inhibitory activity and are useful as therapeutic agents for diseases such as hyperuricacidemia and gout.

  式 (1) 的 1-苯基吡唑化合物： 例如：5-氨基-1-(3-氰基-4-异丁氧基苯基)吡唑-4-羧酸、其光学异构体及其药学上可接受的盐。这些化合物具有黄嘌呤氧化酶抑制活性，可作为高尿酸血症和痛风等疾病的治疗药物。