3-bromomethyl-1-(4-methanesulfonylphenyl)-5-phenyl-1H-pyrazole | 781663-73-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-bromomethyl-1-(4-methanesulfonylphenyl)-5-phenyl-1H-pyrazole
• 英文别名: 3-(Bromomethyl)-1-(4-methylsulfonylphenyl)-5-phenylpyrazole
• CAS: 781663-73-8
• 化学式: C₁₇H₁₅BrN₂O₂S
• 分子量: 391.288
• InChiKey: NYNKMWROQGNRNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  23
• 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：
  60.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,4,5-三甲氧基苯酚 、 3-bromomethyl-1-(4-methanesulfonylphenyl)-5-phenyl-1H-pyrazole 在 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以67%的产率得到1-(4-Methylsulfonylphenyl)-5-phenyl-3-[(3,4,5-trimethoxyphenoxy)methyl]pyrazole
  参考文献：
  名称：

  New COX-2/5-LOX Inhibitors:  Apoptosis-Inducing Agents Potentially Useful in Prostate Cancer Chemotherapy

  摘要：

  The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and in vitro pharmacological properties of diarylpyrazole derivatives that have in their structure key pharmacophoric elements to obtain optimal interaction with subsites of active pockets in both enzyme systems. Using a molecular modeling approach, a set of SAR data is proposed, highlighting the importance of the sulfonyl group of one of the aryl moieties in terms of proliferation inhibition and/or apoptosis induction.

  DOI：

  10.1021/jm0407761
• 作为产物：
  描述：

  ethyl 4-hydroxy-2-oxo-4-phenylbut-3-enoate 在 锂硼氢 、 三苯基膦 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 90.5h， 生成 3-bromomethyl-1-(4-methanesulfonylphenyl)-5-phenyl-1H-pyrazole
  参考文献：
  名称：

  New COX-2/5-LOX Inhibitors:  Apoptosis-Inducing Agents Potentially Useful in Prostate Cancer Chemotherapy

  摘要：

  The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and in vitro pharmacological properties of diarylpyrazole derivatives that have in their structure key pharmacophoric elements to obtain optimal interaction with subsites of active pockets in both enzyme systems. Using a molecular modeling approach, a set of SAR data is proposed, highlighting the importance of the sulfonyl group of one of the aryl moieties in terms of proliferation inhibition and/or apoptosis induction.

  DOI：

  10.1021/jm0407761

文献信息

• BORON COMPOUNDS AS INHIBITORS OF LIPOXYGENASE AND THE LIPOXYGENASE PATHWAY, AND PREPARATION AND USE THEREOF
  申请人：UNIVERSITÄT LEIPZIG

  公开号：US20190055268A1

  公开（公告）日：2019-02-21

  The invention relates to chemical compound of the general structure [A-R 3 —X—R 4 ] where A=[R 1 -R 2 ] or [R 1 ] R 1 =aryl, heteroaryl R 2 =alkyl, aryl, heteroaryl, carbonyl, thiocarbonyl, alkyl ester, alkyl thioester R 3 =O, S, NH X=closo- or nido-boron cluster R 4 = where Z=OH, SH, NH 2 where R 5 is selected from H, alkyl, aryl, heteroaryl, alkyl ether, alkyl thioether, alkylamine and R 6 is selected from alkyl, aryl, heteroaryl, alkyl ether, alkyl thioether, alkylamine and where R 3 and R 4 are in meta or para positions to one another, to a process for preparation thereof and to the use thereof, especially in medicine, for example in the inhibition of lipoxygenase.

  该发明涉及一般结构为[A-R3—X—R4]的化合物，其中A=[R1-R2]或[R1]，R1=芳基，杂环芳基，R2=烷基，芳基，杂环芳基，酰基，硫代酰基，烷基酯，烷基硫酯，R3=O，S，NH，X=closo-或nido-硼簇，R4=其中Z=OH，SH，NH2，R5为H，烷基，芳基，杂环芳基，烷基醚，烷基硫醚，烷基胺，R6为烷基，芳基，杂环芳基，烷基醚，烷基硫醚，烷基胺，且R3和R4相对于彼此处于间位或对位位置，涉及其制备方法及用途，特别是在医学领域，例如在抑制脂氧合酶方面的用途。
• Boron compounds as inhibitors of lipoxygenase and the lipoxygenase pathway, and preparation and use thereof
  申请人：UNIVERSITÄT LEIPZIG

  公开号：US10774097B2

  公开（公告）日：2020-09-15

  The invention relates to chemical compound of the general structure [A-R3—X—R4] where A=[R1-R2] or [R1] R1=aryl, heteroaryl R2=alkyl, aryl, heteroaryl, carbonyl, thiocarbonyl, alkyl ester, alkyl thioester R3=O, S, NH X=closo- or nido-boron cluster R4= where Z=OH, SH, NH2 where R5 is selected from H, alkyl, aryl, heteroaryl, alkyl ether, alkyl thioether, alkylamine and R6 is selected from alkyl, aryl, heteroaryl, alkyl ether, alkyl thioether, alkylamine and where R3 and R4 are in meta or para positions to one another, to a process for preparation thereof and to the use thereof, especially in medicine, for example in the inhibition of lipoxygenase.

  本发明涉及一般结构的化合物 [A-R3-X-R4］ 其中 A=[R1-R2]或[R1］ R1=芳基、杂芳基 R2=烷基、芳基、杂芳基、羰基、硫代羰基、烷基酯、烷基硫酯 R3=O、S、NH X=稠合硼或腈基硼簇 R4= 其中 Z=OH, SH, NH2 其中 R5 选自 H、烷基、芳基、杂芳基、烷基醚、烷基硫醚、烷基胺 R6选自烷基、芳基、杂芳基、烷基醚、烷基硫醚、烷基胺 其中 R3 和 R4 互为元位或对位、 其制备方法及其用途，尤其是在医药方面，例如抑制脂氧合酶。
• BORHALTIGE VERBINDUNGEN ALS INHIBITOREN DER LIPOXYGENASE UND DES LIPOXYGENASEWEGES, DEREN HERSTELLUNG UND VERWENDUNG
  申请人：Universität Leipzig

  公开号：EP3365347B1

  公开（公告）日：2021-05-05
• New COX-2/5-LOX Inhibitors:  Apoptosis-Inducing Agents Potentially Useful in Prostate Cancer Chemotherapy
  作者：Nicole Pommery、Thierry Taverne、Aurélie Telliez、Laurence Goossens、Caroline Charlier、Jean Pommery、Jean-François Goossens、Raymond Houssin、François Durant、Jean-Pierre Hénichart

  DOI：10.1021/jm0407761

  日期：2004.12.1

  The arachidonic acid metabolizing enzymes cyclooxygenase-2 (COX-2) and lipoxygenases (LOXs) have been found to be implicated in a variety of cancers, including prostate cancer. To develop new therapeutic treatments, it therefore seemed interesting to design dual COX-2/5-LOX inhibitors. We report here the synthesis and in vitro pharmacological properties of diarylpyrazole derivatives that have in their structure key pharmacophoric elements to obtain optimal interaction with subsites of active pockets in both enzyme systems. Using a molecular modeling approach, a set of SAR data is proposed, highlighting the importance of the sulfonyl group of one of the aryl moieties in terms of proliferation inhibition and/or apoptosis induction.