5-(2-氟苯基)-5-甲基-2,4-咪唑烷二酮 | 7248-25-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: 5-(2-氟苯基)-5-甲基-2,4-咪唑烷二酮
• 英文名称: (RS)-5-(2-fluoro-phenyl)-5-methyl-imidazolidine-2,4-dione
• 英文别名: (RS)-5-(2-fluorophenyl)-5-methylimidazolidine-2,4-dione；5-(2-fluorophenyl)-5-methylimidazolidine-2,4-dione；5-(2-fluorophenyl)-5-methylhydantoine
• CAS: 7248-25-1
• 化学式: C₁₀H₉FN₂O₂
• mdl: MFCD09736685
• 分子量: 208.192
• InChiKey: PBFDUTCJPOZWIC-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-(2-氟苯基)-5-甲基-2,4-咪唑烷二酮 在 氢氧化钾 、 碳酸氢钠 、 L-脯氨醇 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 52.0h， 生成 (R)-2-乙酰氨基-2-(2-氟苯基)丙酸
  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：

  2'-氟苯乙酮 、 氰化钾 在 碳酸氢铵 作用下， 以 乙醇 、 水 为溶剂， 反应 2.0h， 以77%的产率得到5-(2-氟苯基)-5-甲基-2,4-咪唑烷二酮
  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

• COMPOUNDS USEFUL AS MODULATORS OF TRPM8
  申请人：SENOMYX, INC.

  公开号：US20150376136A1

  公开（公告）日：2015-12-31

  The present invention includes compounds useful as modulators of TRPM8, such as compounds of Formulae (Ia), (Ib) and (Ic), and the subgenus and species thereof; personal products containing those compounds; and the use of those compounds and the personal products, particularly the use of increasing or inducing chemesthetic sensations, such as cooling or cold sensations.

  本发明包括作为TRPM8调节剂有用的化合物，例如式(Ia)、(Ib)和(Ic)的化合物，以及其亚属和种类；含有这些化合物的个人产品；以及利用这些化合物和个人产品，特别是利用增加或诱导化学感觉，如凉爽或冷感觉。
• [EN] 5-ARYL-1-IMINO-1-OXO-[1,2,4]THIADIAZINES<br/>[FR] 5-ARYL-1-IMINO-1-OXO-[1,2,4]THIADIAZINES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2015091595A1

  公开（公告）日：2015-06-25

  The present invention provides a compound of formula I' having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

  本发明提供了具有BACE1抑制活性的化合物I'的化合物，它们的制造，含有它们的药物组合物以及它们作为治疗活性物质的用途。本发明的活性化合物在治疗和/或预防治疗阿尔茨海默病等疾病中是有用的。
• Computer-aided insights into receptor-ligand interaction for novel 5-arylhydantoin derivatives as serotonin 5-HT 7 receptor agents with antidepressant activity
  作者：Katarzyna Kucwaj-Brysz、Rafał Kurczab、Magdalena Jastrzębska-Więsek、Ewa Żesławska、Grzegorz Satała、Wojciech Nitek、Anna Partyka、Agata Siwek、Agnieszka Jankowska、Anna Wesołowska、Katarzyna Kieć-Kononowicz、Jadwiga Handzlik

  DOI：10.1016/j.ejmech.2018.01.093

  日期：2018.3

  5-HT7R in RBA, in particular seven compounds (4, 5, 7, 8 and 10-12,Ki ≤ 10 nM). Antidepressant-like activity in vivo for all tested compounds (5-8) was confirmed. SAR analysis based on both crystallography-supported molecular modeling and RBA results indicated that mono-phenyl substituents at both hydantoin and piperazine are more favorable for 5-HT7R affinity than the di-phenyl ones.

  本文提出了一种计算机辅助的洞察力，发现了铅结构5-（4-氟苯基）-3-（2-羟基-3-（4-（2-甲氧基苯基）哌嗪-1-）的新型类似物的受体-配体相互作用。 （yl）propyl）-5-methylimidazolidine-2,4-dione（1，MF-8），作为搜寻强效和选择性5-羟色胺5-HT7受体（5-HT7R）药物的一部分。设计并合成了新的乙内酰脲衍生物（4-19）。对于5-苯基-3-（2-羟基-3-（4-（2-乙氧基苯基）哌嗪-1-基）丙基）-5-甲基咪唑烷-2,4-二酮（4），通过实验确定了其晶体结构。进行了分子建模研究，包括药效团和基于结构的方法。在放射性配体结合测定法（RBA）中研究了新化合物对5-HT7R的亲和力以及对5-HT1AR，多巴胺D2R和α1-，α2-和β-肾上腺素受体的选择性。评价所选化合物（5-8）在小鼠体内的抗抑郁和抗焦虑作用。大多数测试化合物对RBA中
• [EN] 5-AMINO[1,4]THIAZINES AS BACE 1 INHIBITORS<br/>[FR] 5-AMINO[1,4]THIAZINES COMME INHIBITEURS DE BACE1
  申请人：HOFFMANN LA ROCHE

  公开号：WO2013174781A1

  公开（公告）日：2013-11-28

  The present invention provides a compound of formula I having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

  本发明提供了一种具有BACE1抑制活性的化合物I的公式，其制备方法，含有它们的药物组合物以及它们作为治疗活性物质的用途。本发明的活性化合物在治疗和/或预防治疗例如阿尔茨海默病方面是有用的。
• 5-AMINO[1,4]THIAZINES AS BACE 1 INHIBITORS
  申请人：Hoffmnn-La Roche Inc.

  公开号：US20150141413A1

  公开（公告）日：2015-05-21

  The present invention provides a compound of formula I having BACE1 inhibitory activity, their manufacture, pharmaceutical compositions containing them and their use as therapeutically active substances. The active compounds of the present invention are useful in the therapeutic and/or prophylactic treatment of e.g. Alzheimer's disease.

  本发明提供了一种具有BACE1抑制活性的I式化合物，其制造方法，含有它们的制药组合物以及它们作为治疗活性物质的用途。本发明的活性化合物在治疗和/或预防例如阿尔茨海默病等疾病方面是有用的。