ethyl 4-(2-chloro-6-fluorophenyl)-3-oxobutanoate | 502506-68-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: ethyl 4-(2-chloro-6-fluorophenyl)-3-oxobutanoate
• 英文别名: Ethyl (2-chloro-6-fluorophenyl)acetoacetate
• CAS: 502506-68-5
• 化学式: C₁₂H₁₂ClFO₃
• 分子量: 258.677
• InChiKey: SDKWCBFFYZMDAW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 4-(2-chloro-6-fluorophenyl)-3-oxobutanoate 在 sodium 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 6-[(2-chloro-6-fluorophenyl)methyl]-2-isopropylthiopyrimidin-4(3H)-one
  参考文献：
  名称：

  Exploring the Role of 2-Chloro-6-fluoro Substitution in 2-Alkylthio-6-benzyl-5-alkylpyrimidin-4(3H)-ones: Effects in HIV-1-Infected Cells and in HIV-1 Reverse Transcriptase Enzymes

  摘要：

  A comparison of the effects of the 6-(2-chloro-6-fluorobenzyl)-2-(alkylthio)pyrimidin-4(3H)-ones (2-Cl-6-F-S-DABOs) 7-12 and the related 6-(2,6-difluorobenzyl) counterparts 13-15 in HIV-1 infected cells and in the HIV-1 reverse transcriptase (RT) assays is here described. The new 2-Cl-6-F-S-DABOs showed up to picomolar activity against wt HIV-1. Against clinically relevant HIV-1 mutants and in enzyme assays, the simultaneous C5(methyl)/C6(methyl/ethyl) substitution in the 2-Cl-6-F- and 2,6-F2-benzyl series furnished compounds with the highest, wide-spectrum inhibitory activity against HIV-1. Three representative 2-Cl-6-F-S-DABOs carrying two (9c, 10c) or one (10a) stereogenic centers were resolved into their individual stereoisomers and showed a significant diastereo- and enantioselectivity in HIV-1 inhibition, the highest antiviral activity well correlating with the R absolute configuration to the stereogenic center of the C6-benzylic position in both cellular and enzymatic tests. Application of previously reported COMBINEr protocol on 9c and 10c confirmed the influence of the stereogenic centers on their binding modes in the HIV-1 RT.

  DOI：

  10.1021/jm500284x
• 作为产物：
  描述：

  2-氯-6-氟苯乙酸 在 三乙胺 、 magnesium chloride 作用下， 以 乙腈 为溶剂， 反应 2.5h， 生成 ethyl 4-(2-chloro-6-fluorophenyl)-3-oxobutanoate
  参考文献：
  名称：

  Exploring the Role of 2-Chloro-6-fluoro Substitution in 2-Alkylthio-6-benzyl-5-alkylpyrimidin-4(3H)-ones: Effects in HIV-1-Infected Cells and in HIV-1 Reverse Transcriptase Enzymes

  摘要：

  A comparison of the effects of the 6-(2-chloro-6-fluorobenzyl)-2-(alkylthio)pyrimidin-4(3H)-ones (2-Cl-6-F-S-DABOs) 7-12 and the related 6-(2,6-difluorobenzyl) counterparts 13-15 in HIV-1 infected cells and in the HIV-1 reverse transcriptase (RT) assays is here described. The new 2-Cl-6-F-S-DABOs showed up to picomolar activity against wt HIV-1. Against clinically relevant HIV-1 mutants and in enzyme assays, the simultaneous C5(methyl)/C6(methyl/ethyl) substitution in the 2-Cl-6-F- and 2,6-F2-benzyl series furnished compounds with the highest, wide-spectrum inhibitory activity against HIV-1. Three representative 2-Cl-6-F-S-DABOs carrying two (9c, 10c) or one (10a) stereogenic centers were resolved into their individual stereoisomers and showed a significant diastereo- and enantioselectivity in HIV-1 inhibition, the highest antiviral activity well correlating with the R absolute configuration to the stereogenic center of the C6-benzylic position in both cellular and enzymatic tests. Application of previously reported COMBINEr protocol on 9c and 10c confirmed the influence of the stereogenic centers on their binding modes in the HIV-1 RT.

  DOI：

  10.1021/jm500284x

文献信息

• [DE] VERWENDUNG VON INDOL-3-CARBONSÄUREESTERN ZUR HEMMUNG DER MIKROSOMALEN PROSTAGLANDIN E2 SYNTHASE<br/>[EN] USE OF INDOLE-3-CARBOXYLIC ESTERS FOR INHIBITING MICROSOMAL PROSTAGLANDIN E2 SYNTHASE<br/>[FR] UTILISATION D'ESTERS DE L'ACIDE INDOL-3-CARBOXYLIQUE POUR L'INHIBITION DE LA PROSTAGLANDINE E2 SYNTHASE MICROSOMALE
  申请人：UNIV TUEBINGEN

  公开号：WO2009146696A1

  公开（公告）日：2009-12-10

  Die vorliegende Erfindung betrifft die Verwendung von lndol-3-carbonsäureestern und seiner Derivate zur Hemmung der induzierbaren mikrosomalen Prostaglandin E2 Synthase-1 und/oder zur Hemmung der 5-Lipoxygenase. Insbesondere betrifft die Erfindung die Verwendung von Derivaten des 3-Carboxy-aryl[g]indols, vor allem von 2-Aryl- und 2-Arylalkyl-Aryl[g]indol-3-carbonsäureestern sowie deren strukturellen Abkömmlingen zur Hemmung der induzierbaren mikrosomalen Prostaglandin E2 Synthase-1 und / oder zur Hemmung der 5-Lipoxygenase. Ferner betrifft die Erfindung die Verwendung von lndol-3-carbonsäureestern zur Herstellung eines Arzneimittels zur Behandlung von PGE2- und / oder 5-LO-vermittelter Erkrankungen und krankhafter Zustände, insbesondere von entzündlichen chronischen Entzündungen wie rheumatoide Arthritis, Osteoarthritis, Erkrankungen des kardiovaskulären Systems, Asthma, allergische Rhinitis, Multiple Sklerose, entzündliche Hauterkrankungen, Osteoporose und Krebs, Schmerz und Fieber, bei denen PGE2 und / oder 5-LO Produkte eine Rolle spielen.

  本发明涉及使用indol-3-羧酸酯及其衍生物来抑制可诱导的微粒体前列腺素E2合成酶-1和/或抑制5-脂氧合酶。具体涉及使用3-羧基芳基[g]吲哚的衍生物，特别是2-芳基和2-芳基烷基芳基[g]吲哚-3-羧酸酯及其结构衍生物来抑制可诱导的微粒体前列腺素E2合成酶-1和/或抑制5-脂氧合酶。此外，本发明涉及使用indol-3-羧酸酯来制备药物，用于治疗PGE2和/或5-LO介导的疾病和病态，特别是慢性炎症性疾病，如类风湿性关节炎，骨关节炎，心血管系统疾病，哮喘，过敏性鼻炎，多发性硬化症，炎性皮肤病，骨质疏松症和癌症，以及疼痛和发热，在其中PGE2和/或5-LO产物发挥作用。
• Imidazo[1,2-a]pyrimidine and fungicidal compositions containing thereof
  申请人：——

  公开号：US20040235865A1

  公开（公告）日：2004-11-25

  The imidazo[1,2-a]pyrimidines given by the following formula [I]: 1 wherein R 1 and R 2 represent a C1-C6 alkyl group optionally substituted by one or more selected from the group consisting of C1-C4 alkoxy group, C2-C8 dialkylamino group, C1-C4 alkylthio group, C2-C5 alkoxycarbonyl group, cyano group and halogen atoms; or R 1 and R 2 represent a 3-8 membered heterocyclic group together with the nitrogen atom bonded with R 1 and R 2 ; R 3 represents a halogen atom or C1-C4 alkyl group; and Ar represents a phenyl group optionally substituted by a halogen atom or atoms; and the like] have excellent activity for controlling plant diseases.

  以下式子所示的咪唑[1,2-a]嘧啶化合物 [I]:1具有出色的植物病害控制活性，其中：R1和R2代表C1-C6烷基，可选地被来自C1-C4烷氧基、C2-C8二烷基氨基、C1-C4烷硫基、C2-C5烷氧羰基、氰基和卤素原子的一个或多个选择性取代；或者R1和R2与与其相结合的氮原子共同构成3-8成员的杂环基团；R3代表卤素原子或C1-C4烷基；Ar代表苯基，可选地被一个或多个卤素原子取代；等等。
• 5-Alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3<i>H</i>)-ones, a Series of Anti-HIV-1 Agents of the Dihydro-alkoxy-benzyl-oxopyrimidine Family with Peculiar Structure−Activity Relationship Profile
  作者：Maxim B. Nawrozkij、Dante Rotili、Domenico Tarantino、Giorgia Botta、Alexandre S. Eremiychuk、Ira Musmuca、Rino Ragno、Alberta Samuele、Samantha Zanoli、Mercedes Armand-Ugón、Imma Clotet-Codina、Ivan A. Novakov、Boris S. Orlinson、Giovanni Maga、José A. Esté、Marino Artico、Antonello Mai

  DOI：10.1021/jm800340w

  日期：2008.8.1

  A series of dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) bearing a 2-aryl-2-oxoethylsulfanyl chain at pyrimidine C2, an alkyl group at C5, and a 2,6-dichloro-, 2-chloro-6-fluoro-, and 2,6-difluoro-benzyl substitution at C6 (oxophenethyl-S-DABOs, 6-8) is here described. The new compounds showed low micromolar to low nanomolar (in one case subnanomolar) inhibitory activity against wt HIV-1. Against clinically relevant HIV-1 mutants (K103N, Y181C, and Y188L) as well as in enzyme (wt and K103N, Y181I, and L1001 mutated RTs) assays, compounds carrying an ethylliso-propyl group at C5 and a 2,6-dichloro-/2-chloro-6-fluoro-benzyl moiety at C6 were the most potent derivatives, also characterized by low fold resistance ratio. Interestingly, the structure-activity relationship (SAR) data drawn from this DABO series are more related to HEPT than to DABO derivatives. These findings were at least in part rationalized by the description of a fair superimposition between the 6-8 and TNK-651 (a HEPT analogue) binding modes in both WT and Y181C RTs.
• Exploring the Role of 2-Chloro-6-fluoro Substitution in 2-Alkylthio-6-benzyl-5-alkylpyrimidin-4(3<i>H</i>)-ones: Effects in HIV-1-Infected Cells and in HIV-1 Reverse Transcriptase Enzymes
  作者：Dante Rotili、Domenico Tarantino、Maxim B. Nawrozkij、Alexandre S. Babushkin、Giorgia Botta、Biagina Marrocco、Roberto Cirilli、Sergio Menta、Roger Badia、Emmanuele Crespan、Flavio Ballante、Rino Ragno、José A. Esté、Giovanni Maga、Antonello Mai

  DOI：10.1021/jm500284x

  日期：2014.6.26

  A comparison of the effects of the 6-(2-chloro-6-fluorobenzyl)-2-(alkylthio)pyrimidin-4(3H)-ones (2-Cl-6-F-S-DABOs) 7-12 and the related 6-(2,6-difluorobenzyl) counterparts 13-15 in HIV-1 infected cells and in the HIV-1 reverse transcriptase (RT) assays is here described. The new 2-Cl-6-F-S-DABOs showed up to picomolar activity against wt HIV-1. Against clinically relevant HIV-1 mutants and in enzyme assays, the simultaneous C5(methyl)/C6(methyl/ethyl) substitution in the 2-Cl-6-F- and 2,6-F2-benzyl series furnished compounds with the highest, wide-spectrum inhibitory activity against HIV-1. Three representative 2-Cl-6-F-S-DABOs carrying two (9c, 10c) or one (10a) stereogenic centers were resolved into their individual stereoisomers and showed a significant diastereo- and enantioselectivity in HIV-1 inhibition, the highest antiviral activity well correlating with the R absolute configuration to the stereogenic center of the C6-benzylic position in both cellular and enzymatic tests. Application of previously reported COMBINEr protocol on 9c and 10c confirmed the influence of the stereogenic centers on their binding modes in the HIV-1 RT.