5-methylsulfonyl-2-[5-phenyl-3-difluoromethyl-1H-pyrazol-1-yl]pyridine | 343629-25-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-methylsulfonyl-2-[5-phenyl-3-difluoromethyl-1H-pyrazol-1-yl]pyridine
• 英文别名: 2-(3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine；2-(3-Difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonylpyridine；2-(3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl pyridine；2-[3-(difluoromethyl)-5-phenylpyrazol-1-yl]-5-methylsulfonylpyridine
• CAS: 343629-25-4
• 化学式: C₁₆H₁₃F₂N₃O₂S
• 分子量: 349.361
• InChiKey: LNEWNCVYPLKLFQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  73.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-methylsulfonyl-2-[5-phenyl-3-difluoromethyl-1H-pyrazol-1-yl]pyridine 在 N-氯代丁二酰亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 2-(4-Chloro-3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine
  参考文献：
  名称：

  Discovery of a potent, selective and orally active canine COX-2 inhibitor, 2-(3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine

  摘要：

  Structure-activity relationship (SAR) studies of 2-[3-di(and tri)fluoromethyl-5-arylpyrazol-1-yl]-5-methanesulfonylpyridine derivatives for canine COX enzymes are described. This led to the identification of 12a as a lead candidate for further progression. The in vitro and in vivo activity of 12a for the canine COX-2 enzyme as well as its in vivo efficacy and pharmacokinetic properties in dog are highlighted. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.10.004
• 作为产物：
  描述：

  4,4-二氟-1-苯基-1,3-丁二酮 在 硫酸 作用下， 以 水 、 异丙醇 为溶剂， 生成 5-methylsulfonyl-2-[5-phenyl-3-difluoromethyl-1H-pyrazol-1-yl]pyridine
  参考文献：
  名称：

  Process for preparing heterocyclo-alkysulfonyl pyrazole derivatives

  摘要：

  本发明涉及制备式1:1化合物的过程，以及在这些过程中有用的中间体，其中R1-R4的定义如本文所述。式1的化合物对于治疗或缓解炎症及其他炎症相关疾病有用。

  公开号：

  US20030100765A1

文献信息

• New hydroxy-pyrazoline intermediates, subtle regio-selectivity and relative reaction rate variations observed during acid catalyzed and neutral pyrazole cyclization
  作者：Timothy Norris、Roberto Colon-Cruz、David H. B. Ripin

  DOI：10.1039/b500413f

  日期：——

  capability of the R and Ar substituents. The reaction conditions that caused cyclization to pyrazoles varied from direct condensation of the hydrazine and 1,3-dicarbonyl compounds, to reactions requiring catalytic quantities of sulfuric acid to sulfuric acid in excess. Unexpected regio-selectivity was observed in the case of R = CF3 that depended upon the reaction conditions.

  芳肼4和1,3-二羰基化合物5通过via异构体对6和7失水而反应生成吡唑，这会产生两种可能的区域异构体。有时观察到3-羟基-3,4-二氢吡唑或羟基吡唑啉9和9是稳定的可分离中间体，可以在失去第二分子水生成吡唑10和11之前对其进行充分表征。类型8和9的中间体相对较少。我们研究了其中R = CH3，CHF2和CF3，Ar = Ph和5-甲磺酰基吡啶-2--2-基的反应系列（方案2），并观察了动力学行为和区域异构现象之间的性质差异，具体取决于电子的程度。 R和Ar取代基的吸收能力。导致环化成吡唑的反应条件从肼和1,3-二羰基化合物的直接缩合到需要催化量的硫酸到过量硫酸的反应之间变化。在R ＝ CF 3的情况下，观察到区域选择性超出预期，这取决于反应条件。
• In vitro and in vivo profile of 2-(3-di-fluoromethyl-5-phenylpyrazol-1-yl)-5-methanesulfonylpyridine, a potent, selective, and orally active canine COX-2 inhibitor
  作者：Jin Li、Michael P. Lynch、Kristin Lundy DeMello、Subas M. Sakya、Hengmiao Cheng、Robert J. Rafka、Brian S. Bronk、Burton H. Jaynes、Carolyn Kilroy、Donald W. Mann

  DOI：10.1016/j.bmc.2004.11.048

  日期：2005.3.1

  synthesis of a novel canine COX-2 selective inhibitor, 2-(3-difluoromethyl-5-phenylpyrazol-1-yl)-5-methanesulfonylpyridine, and its in vitro and in vivo profile are described. Pyrazole 8 demonstrated excellent potency and selectivity for canine COX-2 in both in vitro and ex vivo whole blood assays. This novel COX-2 inhibitor also showed a good pharmacokinetic profile (pk) following oral (po), intravenous

  描述了新型犬COX-2选择性抑制剂2-（3-二氟甲基-5-苯基吡唑-1-基）-5-甲磺酰吡啶的合成及其体外和体内特性。吡唑8在体外和离体全血测定中均表现出对犬COX-2的出色效价和选择性。这种新型的COX-2抑制剂在口服（po），静脉内（iv）和皮下（sc）给药后也显示出良好的药代动力学特征（pk），并且在犬滑膜炎模型中显示出出色的体内功效。
• Crystal forms of 2-(3-difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl pyridine
  申请人：——

  公开号：US20040266832A1

  公开（公告）日：2004-12-30

  The invention concerns crystalline forms of 2-(3-difluromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine, their preparation and use in pharmaceuticals.

  该发明涉及2-(3-二氟甲基-5-苯基吡唑-1-基)-5-甲烷磺酰基-吡啶的晶体形式，它们的制备以及在制药中的应用。
• Heterocyclo-alkylsulfonyl pyrazole derivatives as anti-inflammatory/analgesic agents
  申请人：Pfizer Inc.

  公开号：US20030236258A1

  公开（公告）日：2003-12-25

  The present invention relates to compounds of the formula 1 wherein R 2 , R 3 , R 6 and A are defined as in the specification, to pharmaceutical compositions containing them and to their medicinal use. The compounds of the invention are useful in the treatment or alleviation of inflammation and other inflammation associated disorders, such as osteoarthritis, rheumatoid arthritis, colon cancer and Alzheimer's disease, in mammals (preferably humans, dogs, cats and livestock).

  本发明涉及公式1的化合物，其中R2、R3、R6和A如规范中所定义，以及包含它们的药物组合物和它们的医药用途。本发明的化合物对于治疗或缓解哺乳动物（优选为人类、狗、猫和家畜）的炎症和其他与炎症相关的疾病，如骨关节炎、类风湿性关节炎、结肠癌和阿尔茨海默病非常有用。
• Process for preparing heterocyclo-alkylsulfonyl pyrazole derivatives
  申请人：Pfizer Inc

  公开号：US20040044042A1

  公开（公告）日：2004-03-04

  The invention relates to processes for preparing compounds of formula 1: 1 as well as intermediates useful in such processes, wherein R 1 -R 4 are as defined herein. The compounds of formula 1 are useful in the treatment or alleviation of inflammation and other inflammation associated disorders.

  本发明涉及制备式1:1化合物的过程，以及在这些过程中有用的中间体，其中R1-R4如本文所定义。式1的化合物在治疗或缓解炎症和其他与炎症相关的疾病方面有用。