1-(4-(4-甲基-1H-咪唑-1-基)苯基)乙酮 | 142161-53-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(4-(4-甲基-1H-咪唑-1-基)苯基)乙酮
• 英文名称: 4'-(4-methylimidazol-1-yl)acetophenone
• 英文别名: 1-(4-(4-methyl-1H-imidazol-1-yl)phenyl)ethanone；1-[4-(4-methylimidazol-1-yl)phenyl]ethanone
• CAS: 142161-53-3
• 化学式: C₁₂H₁₂N₂O
• 分子量: 200.24
• InChiKey: XVSAOSPGDUFLCH-UHFFFAOYSA-N

物化性质

• 沸点：
  375.3±25.0 °C(Predicted)
• 密度：
  1.11

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2933290090

反应信息

• 作为反应物：
  描述：

  1-(4-(4-甲基-1H-咪唑-1-基)苯基)乙酮 在 氢溴酸 、 溴 、 溶剂黄146 作用下， 以 乙醇 、 氯仿 、 乙酸乙酯 为溶剂， 反应 19.5h， 生成 4-[4-(4-methylimidazol-1-yl)phenyl]-N-(2-methyl-4,5,6,7-tetrahydroindazol-3-yl)-1,3-thiazol-2-amine
  参考文献：
  名称：

  Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators

  摘要：

  The evolution of gamma-secretase modulators (GSMs) through the introduction of novel heterocycles with the goal of aligning activity for reducing the levels of Aβ42 and properties consistent with a drug-like molecule are described. The insertion of a methoxypyridine motif within the tetracyclic scaffold provided compounds with improved activity for arresting Aβ42 production as well as improved properties, including solubility. In vivo pharmacokinetic analysis demonstrated that several compounds within the novel series were capable of crossing the BBB and accessing the therapeutic target. Treatment with methoxypyridine-derived compound 64 reduced Aβ42 levels in the plasma of J20 mice, in addition to reducing Aβ42 levels in the plasma and brain of Tg2576 mice.

  DOI：

  10.1016/j.bmc.2020.115734
• 作为产物：
  描述：

  4-甲基咪唑 、 4-氟苯乙酮 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 以20%的产率得到1-(4-(4-甲基-1H-咪唑-1-基)苯基)乙酮
  参考文献：
  名称：

  1,4-二氢吡啶类作为血小板活化因子的拮抗剂。1. 2-（4-杂环基）苯基衍生物的合成及其构效关系。

  摘要：

  利用多种4'-杂环取代的苯甲酰乙酸乙酯通过Hantzsch合成方法制备了一类对血小板活化因子（PAF）具有拮抗活性的2-（4-杂环基苯基）-1,4-二氢吡啶（2-38） ，芳基或杂芳基醛，以及取代的3-氨基巴豆酰胺或3-氨基巴豆酸酯。评估了结构活性关系，其中通过测定抑制PAF诱导的兔洗涤血小板聚集所需的化合物浓度（IC50）在体外测量PAF拮抗剂活性，并通过确定保护小鼠的口服剂量（ED50）在体内测量PAF拮抗剂活性致命注射PAF。发现二氢吡啶2位上的取代基对于体外和体内活性均很重要，而4位和5位的结构变化具有更大的灵活性。最有效的化合物是4-（2-氯苯基）-1,4-二氢-3-（乙氧羰基）-6-甲基-2- [4-（2-甲基咪唑并[4,5-c]吡啶-1-基）苯基] -5- [N-（2-吡啶基）氨基甲酰基]吡啶（17，UK-74,505），IC50 = 4.3 nM，ED50 = 0.26 mg

  DOI：

  10.1021/jm00095a005

文献信息

• Platelet activating factor antagonists
  申请人：Pfizer Inc.

  公开号：US04935430A1

  公开（公告）日：1990-06-19

  Platelet activating factor antagonists of formula (I): ##STR1## wherein R is phenyl or phenyl substituted by one or more substituents selected from nitro, halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, aryl (C.sub.1 -C.sub.4) alkoxy, fluoro (C.sub.1 -C.sub.4) alkoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulphonyl, hydroxy, trifluoromethyl and cyano, or is phenyl fused to a dioxole ring; R.sup.1 and R.sup.2 are each independently H or C.sub.1 -C.sub.6 alkyl, or R.sup.1 and R.sup.2 together complete a pyrrolidinyl, piperidino, morpholino, piperazinyl, N-(C.sub.1 -C.sub.4 alkyl) piperazinyl or N-(C.sub.2 -C.sub.4 alkanoyl)-piperazinyl group; or R.sup.2 is H or C.sub.1 -C.sub.4 alkyl and R.sup.1 is CN, C.sub.3 -C.sub.7 cycloalkyl, aryl, heteroaryl or a C.sub.1 -C.sub.4 alkyl group substituted by one or more substituents selected from C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.4 alkoxycarbonyl, aryl or heteroaryl; Z is selected from C.sub.1 -C.sub.6 alkoxy, aryl (C.sub.1 -C.sub.4) alkoxy, hydroxy, and --NR.sup.4 R.sup.5 wherein each of R.sup.4 and R.sup.5 is independently H or C.sub.1 -C.sub.6 alkyl, or R.sup.4 and R.sup.5 together complete a pyrrolidinyl, piperidino, morpholino, piperazinyl or N-(C.sub.1 -C.sub.4 alkyl) piperazinyl group; Y is 1,4 phenylene or pyridine-2,5-diyl, and X is a 5 or 6 membered aromatic heterocyclic group containing one or more nitrogen atoms in its ring; which ring may be fused to a benzene ring or to a further 5- or 6-membered aromatic heterocyclic ring containing one or more nitrogen atoms, at least one of said heterocyclic rings optionally also containing an oxygen or sulphur atom, and being optionally substituted with one or more substituents selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, CF.sub.3 and CN; and their pharmaceutically acceptable salts.

  公式（I）的血小板活化因子拮抗剂：其中R是苯基或苯基，其上取代基可从硝基，卤素，C.sub.1-C.sub.4烷基，C.sub.1-C.sub.4烷氧基，芳基（C.sub.1-C.sub.4）烷氧基，氟基（C.sub.1-C.sub.4）烷氧基，C.sub.1-C.sub.4烷基硫基，C.sub.1-C.sub.4烷基磺酰基，羟基，三氟甲基和氰基中选择一个或多个取代基；或者是与二噁唑环融合的苯基；R.sup.1和R.sup.2分别独立地为H或C.sub.1-C.sub.6烷基，或者R.sup.1和R.sup.2一起形成吡咯啉基，哌啶基，吗啉基，哌嗪基，N-(C.sub.1-C.sub.4烷基)哌嗪基或N-(C.sub.2-C.sub.4烷酰基)-哌嗪基；或者R.sup.2为H或C.sub.1-C.sub.4烷基，R.sup.1为CN，C.sub.3-C.sub.7环烷基，芳基，杂环芳基或一个C.sub.1-C.sub.4烷基，其上取代基可从C.sub.3-C.sub.7环烷基，C.sub.1-C.sub.4烷氧羰基，芳基或杂环芳基中选择一个或多个取代基；Z从C.sub.1-C.sub.6烷氧基，芳基（C.sub.1-C.sub.4）烷氧基，羟基和--NR.sup.4R.sup.5中选择，其中R.sup.4和R.sup.5中的每一个独立地为H或C.sub.1-C.sub.6烷基，或者R.sup.4和R.sup.5一起形成吡咯啉基，哌啶基，吗啉基，哌嗪基或N-(C.sub.1-C.sub.4烷基)哌嗪基；Y为1,4-苯基或吡啶-2,5-二基，X为含有一个或多个氮原子的5或6成员芳香杂环基团；该环可能与苯环融合，或与进一步含有一个或多个氮原子的5-或6成员芳香杂环环融合，至少其中一个杂环环可选地还含有一个氧原子或硫原子，并可选地取代一个或多个取代基，所述取代基可从C.sub.1-C.sub.4烷基，C.sub.1-C.sub.4烷氧基，卤素，CF.sub.3和CN中选择；以及其药学上可接受的盐。
• Alkyl 2-benzylidene-4-(2-alkylimidazopyrid-1-yl) benzoylacetate esters
  申请人：Pfizer Inc

  公开号：US05149814A1

  公开（公告）日：1992-09-22

  Intermediates useful in the synthesis of dihydropyridine platelet activating factor antagonists of the formula ##STR1## where R is phenyl or substituted phenyl; R.sup.3 is lower alkyl; Y is 1,4-phenylene and X is 2-alkylimidazopyridyl.

  用于合成二氢吡啶血小板活化因子拮抗剂的中间体，其化学式为##STR1##其中R是苯或取代苯; R.sup.3是较低的烷基; Y是1,4-苯撑基，X是2-烷基咪唑吡啶基。
• 1,4-dihydro-2-(4-[benzimidazol-l-yl]phenyl)-pyridines as platelet
  申请人：Pfizer Inc.

  公开号：US05063237A1

  公开（公告）日：1991-11-05

  Platelet activating factor antagonists of formula (I): ##STR1## wherein R is phenyl or phenyl substituted by one or more substituents selected from nitro, halo, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, aryl(C.sub.1 -C.sub.4)alkoxy, fluoro(C.sub.1 -C.sub.4)alkoxy, C.sub.1 -C.sub.4 alkylthio, C.sub.1 -C.sub.4 alkylsulphonyl, hydroxy, trifluoromethyl and cyano, or is phenyl fused to a dioxole ring; R.sup.1 and R.sup.2 are each independently H or C.sub.1 -C.sub.6 alkyl, or R.sup.1 and R.sup.2 together complete a pyrrolidinyl, piperidino, morpholino, piperazinyl, N-(C.sub.1 -C.sub.4 alkyl)piperazinyl or N-(C.sub.2 -C.sub.4 alkanoyl)-piperazinyl group; R.sup.2 is H or C.sub.1 -C.sub.4 alkyl and R.sup.1 is CN, C.sub.3 -C.sub.7 cycloalkyl, aryl, heteroaryl or a C.sub.1 -C.sub.4 alkyl group substituted by one or more substituents selected from C.sub.3 -C.sub.7 cycloalkyl, C.sub.1 -C.sub.4 alkoxycarbonyl, aryl or heteroaryl; Z is selected from C.sub.1 -C.sub.6 alkoxy, aryl(C.sub.1 -C.sub.4)alkoxy, hydroxy, and --NR.sup.4 R.sup.5 wherein each of R.sup.4 and R.sup.5 is independently H or C.sub.1 -C.sub.6 alkyl, or R.sup.4 and R.sup.5 together complete a pyrrolidinyl, piperidino, morpholino, piperazinyl or N-(C.sub.1 -C.sub.4 alkyl)piperazinyl group; Y is 1,4 phenylene or pyridine-2,5-diyl, X is a 5 or 6 membered aromatic heterocyclic group containing one or more nitrogen atoms in its ring; which ring may be fused to a benzene ring or to a further 5- or 6-membered aromatic heterocyclic ring containing one or more nitrogen atoms, at least one of said heterocyclic rings optionally also containing an oxygen or sulphur atom, and being optionally substituted with one or more substituents selected from C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, halo, CF.sub.3 and CN; and their pharmaceutically acceptable salts.

  公式（I）的血小板活化因子拮抗剂：其中R为苯基或苯基取代物，所述取代物从硝基，卤素，C.sub.1-C.sub.4烷基，C.sub.1-C.sub.4烷氧基，芳基（C.sub.1-C.sub.4）烷氧基，氟代（C.sub.1-C.sub.4）烷氧基，C.sub.1-C.sub.4烷硫基，C.sub.1-C.sub.4烷基磺酰基，羟基，三氟甲基和氰基中选择一个或多个取代；或为融合到二噁英环上的苯基；R.sup.1和R.sup.2各自独立为H或C.sub.1-C.sub.6烷基，或R.sup.1和R.sup.2一起形成吡咯烷基，哌啶基，吗啉基，哌嗪基，N-（C.sub.1-C.sub.4烷基）哌嗪基或N-（C.sub.2-C.sub.4烷酰基）-哌嗪基；其中R.sup.2为H或C.sub.1-C.sub.4烷基，R.sup.1为CN，C.sub.3-C.sub.7环烷基，芳基，杂环芳基或取代一个或多个取代物的C.sub.1-C.sub.4烷基，所述取代物从C.sub.3-C.sub.7环烷基，C.sub.1-C.sub.4烷氧羰基，芳基或杂环芳基中选择一个或多个；Z从C.sub.1-C.sub.6烷氧基，芳基（C.sub.1-C.sub.4）烷氧基，羟基和--NR.sup.4R.sup.5中选择，其中R.sup.4和R.sup.5各自独立为H或C.sub.1-C.sub.6烷基，或R.sup.4和R.sup.5一起形成吡咯烷基，哌啶基，吗啉基，哌嗪基或N-（C.sub.1-C.sub.4烷基）哌嗪基；Y为1,4-苯基或吡啶-2,5-二基，X为含有一个或多个氮原子的5或6元芳香杂环基，其环可以与苯环或另一个含有一个或多个氮原子的5-或6元芳香杂环环融合，所述杂环环中至少有一个可以选择性地含有氧原子或硫原子，并且可以取代一个或多个取代物，所述取代物从C.sub.1-C.sub.4烷基，C.sub.1-C.sub.4烷氧基，卤素，CF.sub.3和CN中选择一个或多个；以及其医药上可接受的盐。
• Alkyl 2-benzylidene-4-(benzimidazol-1-yl) benzoylacetate esters as
  申请人：Pfizer Inc.

  公开号：US05070205A1

  公开（公告）日：1991-12-03

  Intermediates useful in the synthesis of dihydropyridine platelet activating factor antagonists of the formula ##STR1## where R is phenyl or substituted phenyl; R.sup.3 is lower alkyl; Y is 1,4-phenylene and X is a benzimidazol-1-yl.

  在合成二氢吡啶血小板活化因子拮抗剂的中间体中有用的化合物的化学式如下：##STR1## 其中R为苯基或取代苯基；R.sup.3为低碳基；Y为1,4-苯基；X为苯并咪唑-1-基。
• COMPOUNDS AND USES THEREOF IN MODULATING AMYLOID BETA
  申请人：Cheng Soan

  公开号：US20070249833A1

  公开（公告）日：2007-10-25

  Novel compounds, compositions, and kits are provided. Methods of modulating Aβ levels, and methods of treating a disease associated with aberrant Aβ levels are also provided.

  提供了新型化合物、组合物和试剂盒。还提供了调节Aβ水平的方法和治疗与异常Aβ水平相关的疾病的方法。