3-(4-chlorophenyl)-1-([4-(1,1-dimethylethyl)phenyl]methyl)-1H-pyrazole-5-carboxylic acid | 1018479-57-6

• 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-(4-chlorophenyl)-1-([4-(1,1-dimethylethyl)phenyl]methyl)-1H-pyrazole-5-carboxylic acid
• 英文别名: 1-(4-tert-Butylbenzyl)-3-(4-chlorophenyl)-1H-pyrazole-5-carboxylic acid；2-[(4-tert-butylphenyl)methyl]-5-(4-chlorophenyl)pyrazole-3-carboxylic acid
• CAS: 1018479-57-6
• 化学式: C₂₁H₂₁ClN₂O₂
• 分子量: 368.863
• InChiKey: HPNGWYKVIZDDST-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-chlorophenyl)-1-([4-(1,1-dimethylethyl)phenyl]methyl)-1H-pyrazole-5-carboxylic acid 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 [1-(4-tert-butylbenzyl)-3-(4-chlorophenyl)-1H-pyrazol-5-yl][4-(2-fluorophenyl)piperazin-1-yl]methanone
  参考文献：
  名称：

  新型(1-芳甲基-3-芳基-1H-吡唑-5-基)(4-芳基哌嗪-1-基)甲酮衍生物的合成及抗真菌活性

  摘要：

  合成了一系列新型(1-芳基甲基-3-芳基-1H-吡唑-5-基)(4-芳基哌嗪-1-基)甲酮衍生物。构效关系的初步研究表明，4-氯苯基、4-叔丁基苯基、4-氟苯基和3-甲氧基苯基对抗真菌活性具有良好的影响。

  DOI：

  10.3184/174751913x13734652599909
• 作为产物：
  描述：

  对叔丁基氯苄 在 水 、 potassium carbonate 、 potassium hydroxide 作用下， 以 乙腈 为溶剂， 生成 3-(4-chlorophenyl)-1-([4-(1,1-dimethylethyl)phenyl]methyl)-1H-pyrazole-5-carboxylic acid
  参考文献：
  名称：

  Synthesis of pyrazole peptidomimetics and their inhibition against A549 lung cancer cells

  摘要：

  A series of novel pyrazole peptidomimetics was synthesized from 3-aryl-1-arylmethyl-1H-pyrazole-5-carboxylic acid and amino acid ester. Structures of the compounds were characterized by means of IR, H-1 NMR and mass spectroscopy. Compounds 5e and 5k suppress effectively the growth of A549 lung cancer cells. Preliminary research on the mechanism of action showed that the inhibition might perform through combination of apoptosis, autophagy and cell cycle arrest. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.09.032

文献信息

• Synthesis and Discovery of Novel Pyrazole Carboxamide Derivatives as Potential Osteogenesis Inducers
  作者：Hong-Shui Lv、Qian-Qian Han、Xiao-Ling Ding、Ji-Liang Zhou、Pi-Shan Yang、Jun-Ying Miao、Bao-Xiang Zhao

  DOI：10.1002/ardp.201200180

  日期：2012.11

  A series of novel N‐aryl‐3‐aryl‐1‐arylmethyl‐1H‐pyrazole‐5‐carboxamide derivatives 4a–l was synthesized by the reaction of 3‐aryl‐1‐arylmethyl‐1H‐pyrazole‐5‐carbonyl chloride with substituted aniline in good to excellent yields. Structures of the compounds were determined by IR, 1H NMR, and HR‐MS spectroscopy. The molecular structure was confirmed by the X‐ray crystal analysis of one compound (4j)

  3-芳基-1-芳基甲基-1H-吡唑-5-羰基氯与5-甲酰氯反应合成了一系列新型N-芳基-3-芳基-1-芳基甲基-1H-吡唑-5-甲酰胺衍生物4a-l。取代苯胺的产率很好。化合物的结构通过IR、1H NMR和HR-MS光谱确定。分子结构通过一种易于结晶的化合物 (4j) 的 X 射线晶体分析得到证实。这些化合物用于诱导小鼠成骨细胞前体 MC3T3-E1 成为成骨细胞，并通过碱性磷酸酶 (ALP) 活性和骨唾液蛋白 (BSP) 的基因表达来评估诱导作用。结果表明，与阴性对照组相比，化合物4a-d、4g、4h和4k能提高ALP活性，化合物4h是诱导成骨最有效的一种。
• Synthesis of novel pyrazole carboxamide derivatives and discovery of modulators for apoptosis or autophagy in A549 lung cancer cells
  作者：Xiao-Ling Ding、Hai-Yan Zhang、Lei Qi、Bao-Xiang Zhao、Song Lian、Hong-Shui Lv、Jun-Ying Miao

  DOI：10.1016/j.bmcl.2009.07.131

  日期：2009.9

  A series of novel 3-aryl-1-arylmethyl-1H-pyrazole-5-carboxamide derivatives 3a–l, were synthesized by the reaction of 3-aryl-1-arylmethyl-1H-pyrazole-5-carbonyl chloride with substituted amine in excellent yields. The compounds 3e–h could suppress A549 lung cancer cell growth. More interestingly, compounds 3e and 3f might inhibit the A549 cell growth by inducing apoptosis; whereas compounds 3g and

  一系列新的3-芳基-1-芳甲基-1 ħ吡唑-5-甲酰胺衍生物3A -升，由3-芳基-1-芳甲基-1反应，合成ħ吡唑-5-碳酰氯与取代胺，收率极高。化合物3e – h可以抑制A549肺癌细胞的生长。更有趣的是，化合物3e和3f可能通过诱导细胞凋亡来抑制A549细胞的生长。而带有氟基的化合物3g和3h可能通过诱导自噬而抑制A549细胞的生长。
• Synthesis, Structure Characterization, and X-ray Crystallography of Novel 1-Benzyl-3-phenyl-1<i>H</i>-pyrazole-5-carboxylate Derivatives with a Carbohydrate Moiety
  作者：Song Lian、Jin-Ting Liu、Liang-Wen Zheng、Wei-Yong Liu、Bao-Xiang Zhao

  DOI：10.1080/07328303.2011.583371

  日期：2011.1.1

  A series of novel (2S,3R,4S,5R)-3,4,5-triacetoxy-tetrahydro-2H-pyran-2-yl 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylate derivatives (3) were synthesized by the reaction of 2,3,4-tri-O-acetyl-α-D-xylopyranosyl bromide (2) and 1-benzyl-3-phenyl-1H-pyrazole-5-carboxylic acid (1) in the presence of sodium bicarbonate and tetrabutylammonium bromide in dichloromethane at reflux temperature. The structures

  一系列新颖的（2 S，3 R，4 S，5 R）-3,4,5-三乙酰氧基-四氢-2 H-吡喃-2-基1-苄基-3-苯基-1 H-吡唑-5 -羧酸酯衍生物（3）是通过2,3,4-三-O-乙酰基-α-D-吡喃吡喃糖基溴化物（2）与1-苄基-3-苯基-1H-吡唑-5-羧酸的反应合成的在碳酸氢钠和溴化四丁铵存在下，在二氯甲烷中，在回流温度下，酸（1）。新化合物的结构由IR和1确定根据3d和3g的X射线晶体结构，初步确定了H NMR光谱和HR质谱（HRMS）以及木糖环中新生成的手性碳（C-1）的构型。
• Synthesis and biological validation of novel pyrazole derivatives with anticancer activity guided by 3D-QSAR analysis
  作者：Ines Vujasinović、Andrea Paravić-Radičević、Kata Mlinarić-Majerski、Karmen Brajša、Branimir Bertoša

  DOI：10.1016/j.bmc.2012.01.032

  日期：2012.3

  Using literature data on anticancer activity of pyrazole derivatives, 3D-QSAR models were developed and 3D-QSAR analysis was performed. The 3D-QSAR analysis enabled identification of molecular properties that have the highest impact on antitumor activity against lung cancer cells. The results of 3D-QSAR analysis were taken into account while new compounds were designed. Obtained 3D-QSAR models were used for prediction of activity of new compounds. In this way, design of new compounds was guided by 3D-QSAR analysis which was performed on literature data. Ten new pyrazole derivatives were synthesised and their antitumor activities against A549 and NCIH23 lung cancer cells were validated. In order to obtain full profile of anticancer activity, cells viability (MTS) assays were combined with cell proliferation (BrdU) assays which measure actively dividing cells in treated sample. Experimental measurements showed good agreement between predicted and measured activities for majority of compounds. Also, anticancer activities of new pyrazole derivatives pointed to the chemical groups that can be useful in designing antitumor molecules. Substitution of hydrazine linker with rigid, 1,2,4-oxadiazole moiety resulted in compound 10, which has low (if any) cytotoxic activity and high potential cytostatic activity. Therefore, compound 10 presents a good starting point for design of new, more potent and safer anticancer therapeutics. (C) 2012 Elsevier Ltd. All rights reserved.