4-(4-chlorophenyl)-2-[(2,4-dichlorophenyl)-hydrazono]-3-methyl-4-oxobutyric acid ethyl ester | 170937-37-8

• 英文名称: 4-(4-chlorophenyl)-2-[(2,4-dichlorophenyl)-hydrazono]-3-methyl-4-oxobutyric acid ethyl ester
• 英文别名: ethyl 4-(4-chlorophenyl)-2-(2-(2,4-dichlorophenyl)hydrazono)-3-methyl-4-oxobutanoate；ethyl 3-(4-chlorobenzoyl)-2-[(2,4-dichlorophenyl)-hydrazono]-butyrate；Ethyl 4-(4-chlorophenyl)-2-[(2,4-dichlorophenyl)hydrazinylidene]-3-methyl-4-oxobutanoate
• CAS: 170937-37-8
• 化学式: C₁₉H₁₇Cl₃N₂O₃
• 分子量: 427.715
• InChiKey: ZABCQXIFTGVHQM-UHFFFAOYSA-N

物化性质

• 沸点：
  536.3±60.0 °C(Predicted)
• 密度：
  1.34±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  27
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  67.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-(4-chlorophenyl)-2-[(2,4-dichlorophenyl)-hydrazono]-3-methyl-4-oxobutyric acid ethyl ester 在 溶剂黄146 作用下， 反应 24.0h， 以95.7%的产率得到5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-羧酸乙酯
  参考文献：
  名称：

  Design, synthesis and biological evaluation of CB1 cannabinoid receptor ligands derived from the 1,5-diarylpyrazole scaffold

  摘要：

  The CB1 receptor belongs to the G-protein-coupled receptor superfamily. CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. In this study, we report the synthesis and in vitro binding affinity assay of some 1,5-diarylpyrazole scaffold compounds. The binding results showed that some of the target compounds had an excellent potency toward the CB1 receptor with IC(50) values lying at the nanomole level.

  DOI：

  10.3109/14756366.2010.491794
• 作为产物：
  描述：

  5-(4-chlorophenyl)-4-methyl-2,3-furandione 在 三乙胺 作用下， 以 乙醇 为溶剂， 反应 25.0h， 生成 4-(4-chlorophenyl)-2-[(2,4-dichlorophenyl)-hydrazono]-3-methyl-4-oxobutyric acid ethyl ester
  参考文献：
  名称：

  Design, synthesis and biological evaluation of CB1 cannabinoid receptor ligands derived from the 1,5-diarylpyrazole scaffold

  摘要：

  The CB1 receptor belongs to the G-protein-coupled receptor superfamily. CB1 antagonism has been considered as a new therapeutic target for the treatment of obesity. In this study, we report the synthesis and in vitro binding affinity assay of some 1,5-diarylpyrazole scaffold compounds. The binding results showed that some of the target compounds had an excellent potency toward the CB1 receptor with IC(50) values lying at the nanomole level.

  DOI：

  10.3109/14756366.2010.491794

文献信息

• ‘One-pot’ synthesis of 4-substituted 1,5-diaryl-1H-pyrazole-3-carboxylates via lithium tert-butoxide-mediated sterically hindered Claisen condensation and Knorr reaction
  作者：Jian-An Jiang、Wei-Bin Huang、Jiao-Jiao Zhai、Hong-Wei Liu、Qi Cai、Liu-Xin Xu、Wei Wang、Ya-Fei Ji

  DOI：10.1016/j.tet.2012.11.012

  日期：2013.1

  A concise ‘one-pot’ synthesis of a variety of 4-substituted 1,5-diaryl-1H-pyrazole-3-carboxylates has been developed in moderate to good yields with excellent regioselectivity. Less cost lithium tert-butoxide has been identified as a base for sterically hindered Claisen condensation to efficiently generate the labile 3-substituted 4-aryl-2,4-diketoesters. Furthermore, extensive studies lead to a ‘one-pot’

  已经开发了一种简单的“一锅法”合成的各种4-取代的1,5-二芳基-1 H-吡唑-3-羧酸酯，具有中等到良好的产率，具有出色的区域选择性。成本较低的叔丁醇锂已被确定为空间受阻克莱森（Claisen）缩合反应的碱，可有效生成不稳定的3-取代的4-芳基-2,4-二酮酸酯。此外，广泛的研究通过克莱森缩合反应和克诺尔反应相结合而合成“有价值的4-取代的1,5-二芳基-1 H-吡唑-3-羧酸酯”的“一锅法”工艺。
• CANNABINOID RECEPTOR ANTAGONISTS/INVERSE AGONISTS USEFUL FOR TREATING OBESITY
  申请人：McElroy John Francis

  公开号：US20070213302A1

  公开（公告）日：2007-09-13

  The present invention provides novel pyrazoles that are useful as cannabinoid receptor antagonists and pharmaceutical compositions thereof and methods of using the same for treating obesity, diabetes, and/or cardiometabolic disorders.

  本发明提供了一种新型吡唑，可作为大麻素受体拮抗剂，并提供了其药物组合物和治疗肥胖、糖尿病和/或心脏代谢紊乱的方法。
• Synthesis of 3-Substituted Pyrazole Derivatives by Mixed Anhydride Method and Study of Their Antibacterial Activities
  作者：Sushanta Kumar Mishra、Poulomi Majumdar、Rajani Kanta Behera、Ajaya Kumar Behera

  DOI：10.1080/00397911.2013.765483

  日期：2014.1.2

  Abstract A convenient synthesis of 3-substituted pyrazole derivatives by a mixed anhydride method using i-butylchloroformate and N-methylmorpholine at −20 °C in tetrahydrofuran and study of in vitro antibacterial activities of the prepared compounds against Staphylococcus epidermidis, Bacillus subtilis, Pseudomonas aeruginosa, and Proteus valguris by agar-diffusion method were carried out. The results

  摘要 氯甲酸异丁酯和N-甲基吗啉在-20 °C、四氢呋喃中混合酸酐法简便合成3-取代吡唑衍生物，并研究所制备化合物对表皮葡萄球菌、枯草芽孢杆菌、铜绿假单胞菌的体外抗菌活性, 和变形杆菌通过琼脂扩散法进行。结果表明，产品 4a、4b 和 4c 在较高浓度下对所有测试细菌表现出中度至微弱的抑制作用，但 4d 对表皮葡萄球菌 (22 mm) 的抑制效果最佳，而对铜绿假单胞菌 (16 mm) 的抑制作用最差，在最大浓度 (2.5 mg/ml)，活性随着浓度的降低而降低。[本文提供补充材料。去出版商'
• Synthesis and structure–activity relationship of novel diarylpyrazole imide analogues as CB1 cannabinoid receptor ligands
  作者：Kwang-Seop Song、Min Ju Kim、Hee Jeong Seo、Sung-Han Lee、Myung Eun Jung、Soo-Un Kim、Jeongmin Kim、Jinhwa Lee

  DOI：10.1016/j.bmc.2009.03.006

  日期：2009.4

  A myriad of research groups have been engaged in searching for novel CB1 receptor antagonists, since SR141716A (rimonabant), a CB1 receptor antagonist, was discovered for an obesity treatment. In this research, extended series, based on the 1,5-diarylpyrazole template of rimonabant, was synthesized and tested for CB1 receptor binding affinity. In the present study, N-piperidinylcarboxamide group of rimonabant was replaced with the corresponding sulfonamide, imide, N-methylimide and methylenediamide, respectively. The SAR studies to optimize the CB1 binding affinity led to the potent imide derivatives. The in vivo efficacy test of a derivative (16f) gave a promising result for this novel scaffold. In order to explore physicochemical properties (hydrophobic, steric and electronic) of the representative imide derivatives responsible for their CB1 receptor binding affinity, quantitative structure activity relationship (QSAR) studies were performed. Hansch QSAR models, which were moderate in the explanation for SAR, were generated with hydrophobic, steric and electronic properties of substituents. Especially, the Taft Es-based parabolic model was obtained with the best correlation result (r(2) = 0.846). (C) 2009 Elsevier Ltd. All rights reserved.
• WO2008/102367
  申请人：——

  公开号：——

  公开（公告）日：——