5-(4-fluorophenyl)-5-methylhydantoin | 428-22-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 5-(4-fluorophenyl)-5-methylhydantoin
• 英文别名: 5-(4-fluoro-phenyl)-5-methyl-imidazolidine-2,4-dione；5-(4-fluorophenyl)-5-methylimidazolidine-2,4-dione
• CAS: 428-22-8
• 化学式: C₁₀H₉FN₂O₂
• mdl: MFCD00704683
• 分子量: 208.192
• InChiKey: HJCCCQPVRYYYMJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(4-fluorophenyl)-5-methylhydantoin 在 氢氧化钾 、 氢化钾 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 反应 96.0h， 生成 α-(4-diphenylphosphinophenyl)-α-methylglycine
  参考文献：
  名称：

  Water soluble phosphines

  摘要：

  Nucleophilic phosphination of the potassium or sodium salt of the fluorophenylalanines (1a, 2a) or -glycines (3a, 4a) with potassium phosphides Ph(R)PK (R = Me, Ph) yields chiral phosphine ligands (1-7) with amino acid moieties, The X-ray structure of 3 . 2H(2)O (space group Pbca) has been determined showing a betaine type structure for the amino acid moiety. The alpha-methyl derivatives of the phosphinophenylglycines (10, 11) were obtained in an analogous manner as 1-7, ortho- and para-Fluoroacetophenones have been employed as starting material for the syntheses of alpha-[4-fluorophenyl]-alpha-methylglycine (9c) and its ortho-isomer (8c). the X-ray structure of its monohydrate has been determined (space group P (1) over bar). The N-acetyl (3b, 8e) and ester derivatives (3d, 8d) of 3 and 8c are accessible using standard procedures. Resolution of the diastereomeric salt 12 obtained from (S)-(+)-2-hydroxymethylpyrrolidine and racem-8e by fractionated crystallization yielded the (S,R)-isomer. The absolute configuration of(S,R)-12 was determined by X-ray structural analysis (space group P2(1)2(1)2(1)). Cleavage of (S,R)-12 with hydrochloric acid gave enantiopure (R)-8e [alpha](D)(20) = - 30.9 degrees (c = 1, CH3OH). (C) 2000 Elsevier Science S.A. All rights reserved.

  DOI：

  10.1016/s0022-328x(99)00689-0
• 作为产物：
  描述：

  氰化钾 、 4-氟苯乙酮 在 碳酸氢铵 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以68%的产率得到5-(4-fluorophenyl)-5-methylhydantoin
  参考文献：
  名称：

  Water soluble phosphines

  摘要：

  Nucleophilic phosphination of the potassium or sodium salt of the fluorophenylalanines (1a, 2a) or -glycines (3a, 4a) with potassium phosphides Ph(R)PK (R = Me, Ph) yields chiral phosphine ligands (1-7) with amino acid moieties, The X-ray structure of 3 . 2H(2)O (space group Pbca) has been determined showing a betaine type structure for the amino acid moiety. The alpha-methyl derivatives of the phosphinophenylglycines (10, 11) were obtained in an analogous manner as 1-7, ortho- and para-Fluoroacetophenones have been employed as starting material for the syntheses of alpha-[4-fluorophenyl]-alpha-methylglycine (9c) and its ortho-isomer (8c). the X-ray structure of its monohydrate has been determined (space group P (1) over bar). The N-acetyl (3b, 8e) and ester derivatives (3d, 8d) of 3 and 8c are accessible using standard procedures. Resolution of the diastereomeric salt 12 obtained from (S)-(+)-2-hydroxymethylpyrrolidine and racem-8e by fractionated crystallization yielded the (S,R)-isomer. The absolute configuration of(S,R)-12 was determined by X-ray structural analysis (space group P2(1)2(1)2(1)). Cleavage of (S,R)-12 with hydrochloric acid gave enantiopure (R)-8e [alpha](D)(20) = - 30.9 degrees (c = 1, CH3OH). (C) 2000 Elsevier Science S.A. All rights reserved.

  DOI：

  10.1016/s0022-328x(99)00689-0

文献信息

• Rational design in search for 5-phenylhydantoin selective 5-HT7R antagonists. Molecular modeling, synthesis and biological evaluation
  作者：Katarzyna Kucwaj-Brysz、Dawid Warszycki、Sabina Podlewska、Jagna Witek、Karolina Witek、Andrea González Izquierdo、Grzegorz Satała、María I. Loza、Annamaria Lubelska、Gniewomir Latacz、Andrzej J. Bojarski、Marián Castro、Katarzyna Kieć-Kononowicz、Jadwiga Handzlik

  DOI：10.1016/j.ejmech.2016.02.024

  日期：2016.4

  A series of novel arylpiperazine 5-(4-fluorophenyl)-5-methylhydantoins with 2-hydroxypropyl linker (2–15) was synthesized and evaluated on their affinity towards serotonin 5-HT7 receptor (5-HT7R) in comparison to other closely related GPCRs: serotonin 5-HT1A, and dopamine D2 receptors. The functional activity studied through the measurement of 5-HT7R-mediated cyclic AMP production in Human Embryonic

  一系列新颖的芳基哌嗪的5-（4-氟苯基）-5-methylhydantoins与2-羟丙基接头（2 - 15）中的血清素向5-HT的合成和它们的亲和力评估7受体（5-HT 7相比R），以其他密切相关的GPCR：5-羟色胺5-HT 1A和多巴胺D 2受体。通过测量稳定表达人5-HT 7的人胚肾293细胞（HEK293）中5-HT 7 R介导的环AMP产生研究的功能活性证明了它们的拮抗特性。在初步的代谢稳定性研究中，还使用人肝微粒体（HML）检查了铅的结构。特殊分子建模工作流程支持选择合成候选对象的过程，包括组合文库生成，对接和基于机器学习的评估。另外，进行了对5-HT 1A R和D 2 R的选择性以及功能活性的计算机模拟预测。新合成的化合物被证明具有对5-HT 7 R的强亲和力，类似于5-（4-氟苯基）-3-（3-（4-（2-甲氧基苯基）哌嗪-1）的前导结构。 -基）-2-羟丙基）-5-甲基咪唑烷-2
• Fungicidal 2-imidazolin-5-ones and 2-imidazoline-5-thiones
  申请人：Rhone-Poulenc, Inc.

  公开号：US06344564B1

  公开（公告）日：2002-02-05

  Fungicidal 2-imidazolin-5-ones and 2-imidazoline-5-thiones, processes for their preparation, fungicidal compositions containing them, and methods of using them to treat or prevent fungal disease in crops.

  杀真菌剂2-咪唑啉-5-酮和2-咪唑啉-5-硫酮，它们的制备方法，含有它们的杀真菌组合物，以及使用它们来治疗或预防作物真菌病的方法。
• The role of aryl-topology in balancing between selective and dual 5-HT₇R/5-HT_1Aactions of 3,5-substituted hydantoins
  作者：Katarzyna Kucwaj-Brysz、Rafał Kurczab、Ewa Żesławska、Annamaria Lubelska、Małgorzata Anna Marć、Gniewomir Latacz、Grzegorz Satała、Wojciech Nitek、Katarzyna Kieć-Kononowicz、Jadwiga Handzlik

  DOI：10.1039/c8md00168e

  日期：——

  Influence of aromatic rings topology on 5-HT₇/5-HT_1Aactivity, for novel hydantoin derivatives, was examined.

  芳香环拓扑结构对新型咪唑啉衍生物的5-HT₇/5-HT_1A活性的影响进行了研究。
• New enzymatic methods for the synthesis of primary α-aminonitriles and unnatural α-amino acids by oxidative cyanation of primary amines with<scp>d</scp>-amino acid oxidase from porcine kidney
  作者：Nobuhiro Kawahara、Kazuyuki Yasukawa、Yasuhisa Asano

  DOI：10.1039/c6gc02003h

  日期：——

  Oxidation of amino groups in amines or amino acids activates the sp3 C[small alpha]-H bond to form imines, making the alpha carbon atom a preferable target for nucleophilic reagents such as cyanide.

  胺或氨基酸中氨基的氧化会激活sp 3 C [α- H小键]形成亚胺，使α碳原子成为亲核试剂（如氰化物）的优选靶标。
• SAR-studies on the importance of aromatic ring topologies in search for selective 5-HT7 receptor ligands among phenylpiperazine hydantoin derivatives
  作者：Jadwiga Handzlik、Andrzej J. Bojarski、Grzegorz Satała、Monika Kubacka、Bassem Sadek、Abrar Ashoor、Agata Siwek、Małgorzata Więcek、Katarzyna Kucwaj、Barbara Filipek、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.ejmech.2014.01.065

  日期：2014.5

  on newly developed phenylpiperazine derivatives of aromatic methylhydantoin differing in mutual positions of methyl and phenyl moieties. The new compounds were synthesized using Bucherer–Bergs reaction, two-phase alkylation, Mitsunobu reaction and/or an alkylation under microwave irradiation. The compounds developed were assessed on their affinity for serotoninergic receptors 5-HT1A, 5-HT6, 5-HT7 and

  当前的研究集中在新开发的芳族甲基乙内酰脲的苯基哌嗪衍生物，其甲基和苯基部分的相互位置不同。这些新化合物是通过Bucherer-Bergs反应，两相烷基化，Mitsunobu反应和/或微波辐射下的烷基化反应合成的。开发的化合物在其亲和力被评定为血清素受体5-HT 1A，5-HT 6，5-HT 7，α 1个在放射性配体结合测定-ARs。选择的化合物在人类上的抑制作用测试5-HT 3A中所表示的爪蟾卵母细胞，以及对它们的活性在α 1-肾上腺素受体亚型分别在功能和电生理生物测定中。研究最多的化合物均显示出亲和力α 1 -ARs，5-HT 1A，5-HT 7（ķ我 〜0.8-353 nm）的比对5-HT显著更高6个受体。在5-HT非常弱的抑制效果3A在α伴随着高活性1D，观察选择的代表性化合物-AR亚型。在当前系列中，特别是5-（4-氟苯基）-3-（2-羟基-3-（4-（2-甲氧基苯基）哌嗪-1-基）丙基）-5-甲基咪唑烷-2