ethyl 4-(p-chlorophenyl)-2-methyl-3-oxobutyrate | 221121-40-0

• 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-(p-chlorophenyl)-2-methyl-3-oxobutyrate
• 英文别名: Ethyl 4-(4-chlorophenyl)-2-methyl-3-oxobutanoate
• CAS: 221121-40-0
• 化学式: C₁₃H₁₅ClO₃
• 分子量: 254.713
• InChiKey: RWTGICGJUNHQHX-UHFFFAOYSA-N

物化性质

• 沸点：
  330.2±22.0 °C(Predicted)
• 密度：
  1.169±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  ethyl 4-(p-chlorophenyl)-2-methyl-3-oxobutyrate 在 sodium ethanolate 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 生成 2-sec-Butylsulfanyl-6-(4-chloro-benzyl)-5-methyl-3H-pyrimidin-4-one
  参考文献：
  名称：

  5-Alkyl-2-(alkylthio)-6-(2,6-dihalophenylmethyl)-3,4-dihydropyrimidin-4(3H)-ones:  Novel Potent and Selective Dihydro-alkoxy-benzyl-oxopyrimidine Derivatives

  摘要：

  Molecular modeling analysis of compounds belonging to the recently published series of dihydroalkoxy-benzyl-oxopyrimidines (DABOs), such as S-DABOs and DATNOs, gave support to the design of new 2,6-disubstituted benzyl-DABO derivatives as highly potent and specific inhibitors of the HIV-1 reverse transcriptase (RT). To follow up on the novel DABO derivatives, we decided to investigate the effect of electron-withdrawing substituents in the benzyl unit of the S-DABO skeleton versus their anti-HIV-1 activity. Such chemical modifications impacted the inhibitory activity, especially when two halogen units were introduced at positions 2 and 6 in the phenyl portion of the benzyl group bound to C-6 of the pyrimidine ring. Various 5-alkyl-2-(alkyl(or cycloalkyl)thio)-6-(2,B-dichloro(or 2, 6-difluoro)phenylmethyl)-3,4-dihydropyrimidin-4(3H)-ones were then synthesized and tested as anti-HIV-1 agents in both cell-based and enzyme (recombinant reverse transcriptase, rRT) assays. Among the various mono- and disubstituted phenyl derivatives, the most potent were those containing a 6-(2,6-difluorophenylmethyl) substituent (F-DABOs), which showed EC50's ranging between 40 and 90 nM and selectivity indexes up to greater than or equal to 5000. An excellent correlation was found between EC50 and IC50 values which confirmed that these compounds act as inhibitors of the HIV-1 RT. The structure-activity relationships of the newly synthesized pyrimidinones are presented herein.

  DOI：

  10.1021/jm980260f
• 作为产物：
  描述：

  2-溴丙酸乙酯 、 对氯苯乙腈 在 锌 作用下， 以 四氢呋喃 为溶剂， 生成 ethyl 4-(p-chlorophenyl)-2-methyl-3-oxobutyrate
  参考文献：
  名称：

  作为潜在抗菌剂的新型 2-(取代氨基)烷基硫代嘧啶-4(3H)-ones 的合成

  摘要：

  5-烷基-6-(取代苄基)-2-硫尿嘧啶3a，c与(2-氯乙基)二乙胺盐酸盐反应，得到相应的2-(2-二乙氨基)乙基硫嘧啶-4(3H)-酮4a，b。3a-c 与 N-(2-氯乙基)吡咯烷盐酸盐和/或 N-(2-氯乙基)哌啶盐酸盐反应得到相应的 2-[2-(吡咯烷-1-基)乙基]-硫嘧啶-4(3H )-ones 5a–c 和 2-[2-(piperidin-1-yl)ethyl]thiopyrimidin-4(3H)-ones 6a,b，分别。在相同反应条件下用 N-(2-氯乙基)吗啉盐酸盐处理 3a-d 形成相应的 2-[2-(吗啉-4-基)乙基]硫嘧啶 6c-f。另一方面，3a、b与N-(2-溴乙基)邻苯二甲酰亚胺和/或N-(3-溴丙基)邻苯二甲酰亚胺反应以提供相应的2-[2-(N-邻苯二甲酰亚胺)乙基]-嘧啶7a，b 和 2-[3-(N-邻苯二甲酰亚胺)-丙基]嘧啶 7c,d 分别。针对革兰氏阳性菌（金黄色葡萄球菌

  DOI：

  10.3390/molecules19010279

文献信息

• Synthesis of Novel Uracil Non-Nucleosides Analogues of 3,4-Dihydro-2-Alkylthio-6-benzyl-4-oxopyrimidines and 6-benzyl-1-ethoxymethyl-5-isopropyluracil
  作者：Nasser R. El-Brollosy、Mohamed A. Al-Omar、Omar A. Al-Deeb、Ali A. El-Emam、Claus Nielsen

  DOI：10.3184/030823407x210893

  日期：2007.5

  A series of new uracil non-nucleosides analogues of S-DABO's was synthesised by reaction of 5-alkyl-6-(p-chlorobenzyl)-2-thiouracils with chloroethyl dialkylamine hydrochloride, N-(2-chloroethyl)-pyrrolidine hydrochloride, N-(2-chloroethyl)-piperidine hydrochloride or appropriate haloethers. Novel emivirine analogues were synthesised by silylation of 5-alkyl-6-(p-chlorobenzyl)uracils and treatment with

  通过5-烷基-6-(对-氯苄基)-2-硫尿嘧啶与氯乙基二烷基胺盐酸盐、N-(2-氯乙基)-吡咯烷盐酸盐、N反应合成了一系列新的S-DABO的尿嘧啶非核苷类似物-(2-氯乙基)-哌啶盐酸盐或适当的卤醚。通过 5-烷基-6-(对-氯苄基) 尿嘧啶的甲硅烷基化和溴甲基甲基醚、氯甲基乙基醚或苄基氯甲基醚处理合成了新型 emivirine 类似物。化合物 6-(p-chlorobenzyl)-5-ethyl-1-ethyloxymethyluracil (9e) 和 1-benzyloxymethyl-6-(4-chlorobenzyl)-5-ethyluracil (9f) 显示出对野生型 HIV-1 毒株 III B 的活性在 MT-4 细胞中。
• [EN] QUINOLIN-2-ONE COMPOUNDS<br/>[FR] COMPOSÉS DE QUINOLIN-2-ONE
  申请人：ARGENTA ORAL THERAPEUTICS LTD

  公开号：WO2010040989A1

  公开（公告）日：2010-04-15

  A compound of structural formula [1]: in which: A represents a direct bond, an optionally substituted alkylene or alkenylene group, or a group of formula Z-(optionally substituted)alkylene; B represents a direct bond, an optionally substituted alkylene or alkenylene group, or a group of formula Z-(optionally substituted)alkylene or (optionally substituted)alkylene-Z; Z represents an oxygen atom, an NH or N-alkyl group, a group of formula S(O)n, in which n = 0 to 2, or a group of formula -O-SO2-; X represents a carboxylic acid, tetrazole, 3-hydroxyisoxazole, hydroxamic acid, phosphinate, phosphonate, phosphonamide, sulfonic acid or a group of formula C(=O)NHSO2W or SO2NHC(=O)W; W represents an optionally substituted aryl or heteroaryl group or an optionally substituted alkyl group; Y represents an optionally substituted aryl or heteroaryl group, or an optionally substituted aryl-fused-heterocycloalkyl, heteroaryl-fused-cycloalkyl, heteroaryl-fused-heterocycloalkyl, aryl-fused-cycloalkyl or cycloalkyl group; Ra, Rb and Rc independently represent hydrogen, acyl, alkoxy, alkylsulphinyl, alkylsulphonyl, alkylthio, -NH2, aminoalkyl, hydroxyalkyl, arylalkyl, cyano, dialkylamino, halo, haloalkoxy, haloalkyl, alkyl, alkenyl, -OH, -CHO, -NO2, aryl (optionally substituted with alkoxy, haloalkoxy, halogen, alkyl or haloalkyl), heteroaryl (optionally substituted with alkoxy, haloalkoxy, halogen, alkyl or haloalkyl), heterocycloalkyl, aminoacyl, aminosulphonyl, acylamino, sulphonylamino, heteroarylalkyl, cyclic amine, aryloxy, heteroaryloxy, arylalkyloxy or heteroarylalkyloxy;

  结构式[1]的化合物：其中：A代表直链键，可选择取代的烷基或烯基基团，或者公式Z-(可选择取代)烷基；B代表直链键，可选择取代的烷基或烯基基团，或者公式Z-(可选择取代)烷基或(可选择取代)烷基-Z；Z代表氧原子，NH或N-烷基基团，公式S(O)n中的基团，其中n = 0至2，或者公式-O-SO2-的基团；X代表羧酸，四唑，3-羟基异噁唑，羟肟酸，膦酸酯，膦酸酰，膦酰胺，磺酸或者公式C(=O)NHSO2W或SO2NHC(=O)W的基团；W代表可选择取代的芳基或杂环芳基，或者可选择取代的烷基基团；Y代表可选择取代的芳基或杂环芳基，或者可选择取代的芳基-融合-杂环烷基，杂环芳基-融合-环烷基，杂环芳基-融合-杂环烷基，芳基-融合-环烷基或环烷基基团；Ra、Rb和Rc独立地代表氢、酰基、烷氧基、烷基磺酰基、烷基磺基、烷基硫基、-NH2、氨基烷基、羟基烷基、芳基烷基、氰基、二烷基氨基、卤素、卤代烷氧基、卤代烷基、烷基、烯基、-OH、-CHO、-NO2、芳基（可选择取代烷氧基、卤代烷氧基、卤素、烷基或卤代烷基）、杂环芳基（可选择取代烷氧基、卤代烷氧基、卤素、烷基或卤代烷基）、杂环烷基、氨基酰、氨基磺酰、酰胺基、磺酰胺基、杂环芳基烷基、环胺基、芳氧基、杂环氧基、芳基烷氧基或杂环芳基烷氧基；
• Synthesis of Novel 2-(Substituted amino)alkylthiopyrimidin-4(3H)-ones as Potential Antimicrobial Agents
  作者：Mohamed Attia、Ali El-Emam、Abdulghafoor Al-Turkistani、Amany Kansoh、Nasser El-Brollosy

  DOI：10.3390/molecules19010279

  日期：——

  5-Alkyl-6-(substituted benzyl)-2-thiouracils 3a,c were reacted with (2-chloroethyl) diethylamine hydrochloride to afford the corresponding 2-(2-diethylamino)ethylthiopyrimidin-4(3H)-ones 4a,b. Reaction of 3a–c with N-(2-chloroethyl)pyrrolidine hydrochloride and/or N-(2-chloroethyl)piperidine hydrochloride gave the corresponding 2-[2-(pyrrolidin-1-yl)ethyl]-thiopyrimidin-4(3H)-ones 5a–c and 2-[2-(piperi

  5-烷基-6-(取代苄基)-2-硫尿嘧啶3a，c与(2-氯乙基)二乙胺盐酸盐反应，得到相应的2-(2-二乙氨基)乙基硫嘧啶-4(3H)-酮4a，b。3a-c 与 N-(2-氯乙基)吡咯烷盐酸盐和/或 N-(2-氯乙基)哌啶盐酸盐反应得到相应的 2-[2-(吡咯烷-1-基)乙基]-硫嘧啶-4(3H )-ones 5a–c 和 2-[2-(piperidin-1-yl)ethyl]thiopyrimidin-4(3H)-ones 6a,b，分别。在相同反应条件下用 N-(2-氯乙基)吗啉盐酸盐处理 3a-d 形成相应的 2-[2-(吗啉-4-基)乙基]硫嘧啶 6c-f。另一方面，3a、b与N-(2-溴乙基)邻苯二甲酰亚胺和/或N-(3-溴丙基)邻苯二甲酰亚胺反应以提供相应的2-[2-(N-邻苯二甲酰亚胺)乙基]-嘧啶7a，b 和 2-[3-(N-邻苯二甲酰亚胺)-丙基]嘧啶 7c,d 分别。针对革兰氏阳性菌（金黄色葡萄球菌
• 5-Alkyl-2-(alkylthio)-6-(2,6-dihalophenylmethyl)-3,4-dihydropyrimidin-4(3<i>H</i>)-ones:  Novel Potent and Selective Dihydro-alkoxy-benzyl-oxopyrimidine Derivatives
  作者：Antonello Mai、Marino Artico、Gianluca Sbardella、Silvio Massa、Ettore Novellino、Giovanni Greco、Anna Giulia Loi、Enzo Tramontano、Maria Elena Marongiu、Paolo La Colla

  DOI：10.1021/jm980260f

  日期：1999.2.1

  Molecular modeling analysis of compounds belonging to the recently published series of dihydroalkoxy-benzyl-oxopyrimidines (DABOs), such as S-DABOs and DATNOs, gave support to the design of new 2,6-disubstituted benzyl-DABO derivatives as highly potent and specific inhibitors of the HIV-1 reverse transcriptase (RT). To follow up on the novel DABO derivatives, we decided to investigate the effect of electron-withdrawing substituents in the benzyl unit of the S-DABO skeleton versus their anti-HIV-1 activity. Such chemical modifications impacted the inhibitory activity, especially when two halogen units were introduced at positions 2 and 6 in the phenyl portion of the benzyl group bound to C-6 of the pyrimidine ring. Various 5-alkyl-2-(alkyl(or cycloalkyl)thio)-6-(2,B-dichloro(or 2, 6-difluoro)phenylmethyl)-3,4-dihydropyrimidin-4(3H)-ones were then synthesized and tested as anti-HIV-1 agents in both cell-based and enzyme (recombinant reverse transcriptase, rRT) assays. Among the various mono- and disubstituted phenyl derivatives, the most potent were those containing a 6-(2,6-difluorophenylmethyl) substituent (F-DABOs), which showed EC50's ranging between 40 and 90 nM and selectivity indexes up to greater than or equal to 5000. An excellent correlation was found between EC50 and IC50 values which confirmed that these compounds act as inhibitors of the HIV-1 RT. The structure-activity relationships of the newly synthesized pyrimidinones are presented herein.