5-(4-fluoro-phenyl)-1,3-dimethyl-1H-pyrazole

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(4-fluoro-phenyl)-1,3-dimethyl-1H-pyrazole
• 英文别名: 5-(4-fluorophenyl)-1,3-dimethyl-1H-pyrazole；5-(4-fluorophenyl)-1,3-dimethylpyrazole
• 化学式: C₁₁H₁₁FN₂
• mdl: MFCD09033411
• 分子量: 190.22
• InChiKey: VLDKNBJBPFACAF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.181
• 拓扑面积：
  17.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(4-fluoro-phenyl)-1,3-dimethyl-1H-pyrazole 在 potassium phosphate 、 N-溴代丁二酰亚胺(NBS) 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 乙二醇二甲醚 、 乙腈 为溶剂， 反应 15.17h， 生成 5-Chloro-6-[5-(4-fluorophenyl)-1,3-dimethyl-1H-pyrazol-4-yl]-2H-1,4-benzoxazin-3(4H)-one
  参考文献：
  名称：

  PYRAZOLE COMPOUNDS

  摘要：

  本发明涉及其中每个符号如规范中定义的。该化合物具有优越的矿物皮质激素受体拮抗作用，并可用作通过矿物皮质激素受体激活介导的疾病或病况的预防或治疗剂。

  公开号：

  US20100094000A1
• 作为产物：
  描述：

  1,3-二甲基吡唑-5-酮 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 1,1'-双(二苯基膦)二茂铁 、 potassium phosphate 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 16.0h， 生成 5-(4-fluoro-phenyl)-1,3-dimethyl-1H-pyrazole
  参考文献：
  名称：

  Palladium-Catalyzed Coupling of Pyrazole Triflates with Arylboronic Acids

  摘要：

  A general protocol for the palladium-mediated Suzuki coupling reaction of pyrazole triflates and aryl boronic acids has been developed. The use of additional dppf ligand was determined to increase product yields allowing for the use of a broad range of reaction substrates.

  DOI：

  10.1021/jo0477897

文献信息

• Discovery of 6-[5-(4-fluorophenyl)-3-methyl-pyrazol-4-yl]-benzoxazin-3-one derivatives as novel selective nonsteroidal mineralocorticoid receptor antagonists
  作者：Tomoaki Hasui、Norio Ohyabu、Taiichi Ohra、Koji Fuji、Takahiro Sugimoto、Jun Fujimoto、Kouhei Asano、Masato Oosawa、Sachiko Shiotani、Nobuhiro Nishigaki、Keiji Kusumoto、Hideki Matsui、Atsushi Mizukami、Noriyuki Habuka、Satoshi Sogabe、Satoshi Endo、Midori Ono、Christopher S. Siedem、Tony P. Tang、Cassandra Gauthier、Lisa A. De Meese、Steven A. Boyd、Shoji Fukumoto

  DOI：10.1016/j.bmc.2014.07.038

  日期：2014.10

  In the course of our study on selective nonsteroidal mineralocorticoid receptor (MR) antagonists, a series of novel benzoxazine derivatives possessing an azole ring as the core scaffold was designed for the purpose of attenuating the partial agonistic activity of the previously reported dihydropyrrol-2-one derivatives. Screening of alternative azole rings identified 1,3-dimethyl pyrazole 6a as a lead compound with reduced partial agonistic activity. Subsequent replacement of the 1-methyl group of the pyrazole ring with larger lipophilic side chains or polar side chains targeting Arg817 and Gln776 increased MR binding activity while maintaining the agonistic response at the lower level. Among these compounds, 6-[1-(2,2-difluoro-3-hydroxypropyl)-5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]-2H-1,4-benzoxazin-3(4H)-one (37a) showed highly potent in vitro activity, high selectivity versus other steroid hormone receptors, and good pharmacokinetic profiles. Oral administration of 37a in deoxycorticosterone acetate-salt hypertensive rats showed a significant blood pressure-lowering effect with no signs of antiandrogenic effects. (C) 2014 Elsevier Ltd. All rights reserved.
• PYRAZOLE COMPOUNDS
  申请人：FUKUMOTO Shoji

  公开号：US20100094000A1

  公开（公告）日：2010-04-15

  The present invention relates to wherein each symbol is as defined in the specification. The compound has a superior mineralocorticoid receptor antagonistic action and is useful as an agent for the prophylaxis or treatment of a disease or condition mediated by the mineralocorticoid receptor activation.

  本发明涉及其中每个符号如规范中定义的。该化合物具有优越的矿物皮质激素受体拮抗作用，并可用作通过矿物皮质激素受体激活介导的疾病或病况的预防或治疗剂。
• Palladium-Catalyzed Coupling of Pyrazole Triflates with Arylboronic Acids
  作者：Curt A. Dvorak、Dale A. Rudolph、Sandy Ma、Nicholas I. Carruthers

  DOI：10.1021/jo0477897

  日期：2005.5.1

  A general protocol for the palladium-mediated Suzuki coupling reaction of pyrazole triflates and aryl boronic acids has been developed. The use of additional dppf ligand was determined to increase product yields allowing for the use of a broad range of reaction substrates.