N-benzoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-2-pyrazoline

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-benzoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-2-pyrazoline
• 英文别名: N-benzoyl-5-(4’-chlorophenyl)-3-phenyl-2-pyrazoline；(5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)(phenyl)methanone；1-benzoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-1H-pyrazole；[3-(4-chlorophenyl)-5-phenyl-3,4-dihydropyrazol-2-yl]-phenylmethanone
• 化学式: C₂₂H₁₇ClN₂O
• 分子量: 360.843
• InChiKey: YREKUTRUZDJUJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  32.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-氯查耳酮 、 苯甲酰肼 在 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 6.0h， 以80.13%的产率得到N-benzoyl-5-(4-chlorophenyl)-3-phenyl-4,5-dihydro-2-pyrazoline
  参考文献：
  名称：

  N-formylpyrazolines and N-benzoylpyrazolines as novel inhibitors of mammalian cathepsin B and cathepsin H

  摘要：

  Cathepsins, intracellular proteases, are known to be involved in a number of physiological processes ranging from degradation of extracellular proteins, prohormone processing, progressions of atherosclerosis, etc. High levels of cathepsins have been indicated in various pathological conditions like arthritis, cancer and other tissue degenerative disorders. One of the reasons attributed to these high levels is decrease in inhibitor concentration. Therefore, the work on the identification of small molecular weight compounds as inhibitors of cysteine proteases is of great therapeutic significance. Exploring this work in the same direction, we here present the synthesis of substituted N-formylpyrazolines and N-benzoylpyrazolines and study these as inhibitors to cysteine proteases. After a preliminary screening of the compounds as inhibitors to cysteine proteases in general, studies were carried out to study their inhibitory effects on cathepsin B and cathepsin H. SAR studies show that N-formylpyrazolines were better inhibitors than N-benzoylpyrazolines. The most potent inhibitors among the two series were nitro substituted compounds 1i and 2i with K-i values of similar to 1.1 x 10 (9) M and 19.5 x 10 (8) M for cathepsin B and K-i values of similar to 5.19 x 10 (8) M and 9.8 x 10 (7) M for cathepsin H, respectively. Docking experiments showing interaction between N-formylpyrazolines and N-benzoylpyrazolines with enzyme active sites structures also provided useful insights. (C) 2014 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2014.07.012

文献信息

• Identification of Compounds with Anti-West Nile Virus Activity
  作者：John R. Goodell、Francesc Puig-Basagoiti、Brett M. Forshey、Pei-Yong Shi、David M. Ferguson

  DOI：10.1021/jm051229y

  日期：2006.3.1

  The lack of antiviral compounds targeting flaviviruses represents a significant problem in the development of strategies for treating West Nile Virus (WNV), Dengue, and Yellow Fever infections. Using WNV high-throughput screening techniques developed in Our laboratories, we report the identification of several small molecule anti-WNV compounds belonging to four different structural classes including pyrazolines, xanthanes, acridines, and quinolines. The initial set of "hits" was further refined using cell viability-cytotoxicity assays to two 1,3,5-triaryl pyrazoline compounds: 1-(4-chlorophenylacetyl)-5-(4-nitrophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole and 1-benzoyl-5-(4-chlorophenyl)-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazole. On the basis of their activity and favorable therapeutic indexes, these compounds were identified as viable leads and subjected to additional evaluation using an authentic viral titer reduction assay employing an epidemic strain of WNV. The compounds were further evaluated in a transient replicon reporting system to gain insight into the mechanism of action by identifying the step at which inhibition takes place during viral replication. The results indicate the pyrazolines inhibit RNA synthesis, pointing to viral RNA polymerase, RNA helicase, or other viral replication enzymes as potential targets. Progress was also made in understanding the structural requirements for activity by synthesizing a focused chemical library of substituted pyrazolines. Preliminary SAR data are presented that show the aryl-rings are required for activity against WNV. More importantly, the results indicate WNV activity is tolerant to aryl-substitutions paving the way for the design and development of much larger combinatorial libraries with varied physicochemical properties.
• [EN] ANTI-VIRAL COMPOUINDS<br/>[FR] COMPOSES ANTIVIRAUX
  申请人：UNIV MINNESOTA

  公开号：WO2007038425A2

  公开（公告）日：2007-04-05

  [EN] The invention provides anti-viral compounds of formula (I) wherein R₁-R₃ and A have any of the values defined herein. The invention also provides pharmaceutical compositions comprising such compounds as well as methods for treating viral infections by administering such compounds to an animal.
  [FR] L'invention concerne des composés antiviraux de formule (I), dans laquelle R₁ à R₃ et A sont tels que définis dans la description. L'invention concerne également des compositions pharmaceutiques comprenant ces composés, ainsi que des méthodes de traitement d'infections virales par administration desdits composés à un animal.
• N-formylpyrazolines and N-benzoylpyrazolines as novel inhibitors of mammalian cathepsin B and cathepsin H
  作者：N. Raghav、S. Garg

  DOI：10.1016/j.bioorg.2014.07.012

  日期：2014.12

  Cathepsins, intracellular proteases, are known to be involved in a number of physiological processes ranging from degradation of extracellular proteins, prohormone processing, progressions of atherosclerosis, etc. High levels of cathepsins have been indicated in various pathological conditions like arthritis, cancer and other tissue degenerative disorders. One of the reasons attributed to these high levels is decrease in inhibitor concentration. Therefore, the work on the identification of small molecular weight compounds as inhibitors of cysteine proteases is of great therapeutic significance. Exploring this work in the same direction, we here present the synthesis of substituted N-formylpyrazolines and N-benzoylpyrazolines and study these as inhibitors to cysteine proteases. After a preliminary screening of the compounds as inhibitors to cysteine proteases in general, studies were carried out to study their inhibitory effects on cathepsin B and cathepsin H. SAR studies show that N-formylpyrazolines were better inhibitors than N-benzoylpyrazolines. The most potent inhibitors among the two series were nitro substituted compounds 1i and 2i with K-i values of similar to 1.1 x 10 (9) M and 19.5 x 10 (8) M for cathepsin B and K-i values of similar to 5.19 x 10 (8) M and 9.8 x 10 (7) M for cathepsin H, respectively. Docking experiments showing interaction between N-formylpyrazolines and N-benzoylpyrazolines with enzyme active sites structures also provided useful insights. (C) 2014 Elsevier Inc. All rights reserved.