ethyl 4-(4-chlorophenyl)-3-methyl-2,4-dioxobutanoate lithium salt | 1012314-40-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: ethyl 4-(4-chlorophenyl)-3-methyl-2,4-dioxobutanoate lithium salt
• 英文别名: ethyl 4-(4-chlorophenyl)-3-methyl-4-oxydo-2-oxobuten-3-oate lithium salt；lithium salt of ethyl 4-(4-chlorophenyl)-3-methyl-2-oxo-4-oxydobut-3-enoate；lithium salt of ethyl 4-(4-chlorophenyl)-3-methyl-4-oxydo-2-oxobuten-3-oate；Lithium salt of ethyl 4-(4-chlorophenyl)-3-methyl-4-oxido-2-oxobut-3-enoate；4-(4-chloro-phenyl)-3-methyl-2,4-dioxo-butyric acid ethyl ester lithium salt；ethyl 4-(4-chlorophenyl)-3-methyl-2,4-dioxobutanoate lithium enolate；Lithium;1-(4-chlorophenyl)-4-ethoxy-2-methyl-3,4-dioxobut-1-en-1-olate
• CAS: 1012314-40-7
• 化学式: C₁₃H₁₂ClO₄*Li
• 分子量: 274.63
• InChiKey: LILRCRSPASZOTG-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  -1.43
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  66.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-(4-chlorophenyl)-3-methyl-2,4-dioxobutanoate lithium salt 在 硫酸 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 18.0h， 生成 利莫那班
  参考文献：
  名称：

  Discovery of Rimonabant and its potential analogues as anti-TB drug candidates

  摘要：

  Rimonabant and its analogues have been synthesized in moderate to good yields using a simple synthetic route. All the newly synthesized compounds were subjected to in vitro screening against M. tuberculosis and M. smegmatis. The most potent analogue JMG-14 exhibits MIC value of 3.13 compared to 3.25 and 50 A mu g/ml for ethambutol and pyrazinamide, respectively. The molecular docking reveals that pyrazole ring, number and position of halogen atoms play a crucial role in deciding interactions with MTCYP-121. These findings open up a new avenue in the search of potent anti-TB drugs with rimonabant and its novel analogue JMG-14 as lead molecules.

  DOI：

  10.1007/s00044-015-1346-4
• 作为产物：
  描述：

  草酸二乙酯 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 16.75h， 生成 ethyl 4-(4-chlorophenyl)-3-methyl-2,4-dioxobutanoate lithium salt
  参考文献：
  名称：

  (1,5-DIPHENYL-1H-PYRAZOL-3-YL)OXADIAZOLE DERIVATIVES, PREPARATION METHOD THEREOF AND USE OF SAME IN THERAPEUTICS

  摘要：

  该发明涉及具有以下化学式（I）的化合物：其中R1、R2、R3和R4如本文所定义。该发明还涉及制备所述化合物的方法以及在治疗中的应用。

  公开号：

  US20080039510A1

文献信息

• Imidazol-4-one and Imidazole-4-thione Compounds
  申请人：Shia Kak-Shan

  公开号：US20100113546A1

  公开（公告）日：2010-05-06

  Imidazol-4-one or imidazole-4-thione compounds of formula (I): wherein X, R 1 , R 2 , R 3 , R 4 , R 5 , and R 6 are defined herein. Also disclosed is a method for treating a cannabinoid receptor-mediated disorder with these compounds.

  咪唑-4-酮或咪唑-4-硫酮化合物的化学式（I）：其中X，R1，R2，R3，R4，R5和R6在此定义。还揭示了使用这些化合物治疗大麻素受体介导的疾病的方法。
• [EN] 5-PHENYL-ISOXAZOLE-3-CARBOXAMIDE DERIVATIVES AS TRPV1 MODULATORS<br/>[FR] DÉRIVÉS D'ISOXAZOLE-3-CARBOXAMIDE
  申请人：ORGANON NV

  公开号：WO2009016241A1

  公开（公告）日：2009-02-05

  The present invention relates to isoxazole-3-carboxamide derivative having the general Formula (I), or a pharmaceutically acceptable salt thereof, to pharmaceutical compositions comprising the same, as well as to the use of said isoxazole-3-carboxamide derivatives for the treatment of TRPV1 mediated disorders, such as acute and chronic pain disorders, acute and chronic neuropathic pain, acute and chronic inflammatory pain, respiratory diseases, and lower urinary tract disorders.

  本发明涉及具有通式（I）的异噁唑-3-羧酰胺衍生物，或其药学上可接受的盐，包括含有相同成分的药物组合物，以及所述异噁唑-3-羧酰胺衍生物用于治疗TRPV1介导的疾病，如急性和慢性疼痛疾病、急性和慢性神经病性疼痛、急性和慢性炎症性疼痛、呼吸道疾病和下尿路疾病。
• An Efficient One-pot Synthesis of Aryl-substituted 1-(Thiazol-2-yl)-1<i>H</i>-pyrazole-3-carboxylates via a Hantzsch Synthesis-Knorr Reaction Sequence
  作者：Chunhui Gu、Jiaojiao Zhai、Jianan Jiang、Hongwei Liu、Lei Wang、Dunru Zhu、Yafei Ji

  DOI：10.1002/cjoc.201300878

  日期：2014.2

  carbothioamide afforded 4‐aryl‐2‐(2‐(propan‐2‐ylidene)hydrazinyl)thiazoles via a Hantzsch‐thiazole synthesis, which reacted with 4‐aryl‐2,4‐diketoesters via a sequential Knorr‐pyrazole reaction to deliver a variety of aryl‐substituted ethyl 1‐(thiazol‐2‐yl)‐1H‐pyrazole‐3‐carboxylates in a one‐pot fashion with moderate to high yields. The key intermediates 4‐aryl‐2,4‐diketoesters, existing as its enolic lithium

  通过Hantzsch-噻唑合成反应处理α-溴代烷基芳基酮和2-（丙烷-2-亚烷基）肼碳硫代酰胺得到4-芳基-2-（2-（丙烷-2-亚烷基）肼基）噻唑通过顺序的克诺尔-吡唑反应以单锅方式以适度的温和性输送各种芳基取代的1-（噻唑-2-基）-1H-吡唑-3-羧酸酯的4-芳基-2,4-二酮酸酯高产。现有的关键中间体4-芳基-2,4-二酮酸酯是烯醇式锂盐，是通过烷基苯酮和草酸二乙酯的高产率叔丁基醇介导的克莱森缩合反应原位合成的。这类优雅的分子在两个不同的杂环核上均包含芳基，并且两个代表性分子的构型是通过单晶X射线晶体学确定的。
• The pentafluorosulfanyl group in cannabinoid receptor ligands: synthesis and comparison with trifluoromethyl and tert-butyl analogues
  作者：Stefano Altomonte、Gemma L. Baillie、Ruth A. Ross、Jennifer Riley、Matteo Zanda

  DOI：10.1039/c4ra01212g

  日期：——

  Functional β-arrestin recruitment assays were used to determine equilibrium dissociation constants (Kb) and showed that all of the tested SF5 and CF3 compounds are CB1 neutral antagonists. These results confirm the possibility of successfully using an aromatic SF5 group as a stable, synthetically accessible and effective bioisosteric analogue of the electron-withdrawing CF3 group, and possibly also

  有效地合成了一系列在吡唑环的3位带有间位和对位取代的五氟硫烷基（SF 5）苯胺基团的大麻素配体，并将其与确切的三氟甲基和叔丁基类似物进行了比较。通常，SF 5取代的配体显示出比CF 3对应物更高的亲脂性（即log  P值），并且比叔丁基显示出更低的亲脂性。就药理活性而言，SF 5吡唑通常显示出略高或相当的CB 1受体亲和力（K i），始终在纳摩尔范围内，相对于CF 3和叔丁基类似物对CB 2的选择性。功能性β-arrestin募集测定用于确定平衡解离常数（K b），结果表明所有测试的SF 5和CF 3化合物均为CB 1中性拮抗剂。这些结果证实了成功地将芳香族SF 5基团用作吸电子CF 3基团以及可能还有庞大的脂肪族基团的稳定，合成易得和有效的生物等排类似物的可能性，以用于药物发现和开发应用。
• 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.