5-(P-甲氧基苯基)-5-甲基海因 | 22927-78-2

• 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-(P-甲氧基苯基)-5-甲基海因
• 英文名称: 5-(4-methoxyphenyl)-5-methyl-2,4-imidazolidinedione
• 英文别名: 5-(4-methoxyphenyl)-5-methylimidazolidine-2,4-dione；5-(4-methoxyphenyl)-5-methylhydantoin；5-(4-methoxy-phenyl)-5-methyl-imidazolidine-2,4-dione；5-(4-Methoxy-phenyl)-5-methyl-imidazolidin-2,4-dion；5-methyl-5-(4-methoxyphenyl)hydantoin
• CAS: 22927-78-2
• 化学式: C₁₁H₁₂N₂O₃
• mdl: MFCD00068872
• 分子量: 220.228
• InChiKey: BVKMJNLLWFFTEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  67.4
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  5-(P-甲氧基苯基)-5-甲基海因 在 盐酸 、 R(+)-alpha-甲基苄胺 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 67.75h， 生成 (R)-1-carboxy-1-(4-methoxyphenyl)ethyl ammonium hydrochloride
  参考文献：
  名称：

  Discovery of Diarylhydantoins as New Selective Androgen Receptor Modulators

  摘要：

  A novel selective androgen receptor modulator scaffold has been discovered through structural modifications of hydantoin antiandrogens. Several 4-(4-hydroxyphenyl)-N-arylhydantoins displayed partial agonism with nanomolar in vitro potency in transactivation experiments using androgen receptor (AR) transfected cells. In a standard castrated male rat model, several compounds showed good anabolic activity on levator ani muscle, dissociated from the androgenic activity on ventral prostate, after oral dosing at 30 mg/kg. (+)-4-[3,4-Dimethyl-2,5-dioxo-4-(4-hydroxyphenyl)imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile ((+)-11b) displayed anabolic potency with a strong dissociation between levator ani muscle and ventral prostate (A(50) = 0.5 mg/kg vs 70 mg/kg). The binding modes of two compounds, including (+)-11b, within the AR ligand-binding domain have been studied by cocrystallization experiments using a coactivator-like peptide. Both compounds bound to the same site, and the overall structures of the AR were very similar.

  DOI：

  10.1021/jm300249m
• 作为产物：
  描述：

  苯甲醚 在 aluminum (III) chloride 、 碳酸二甲酯 作用下， 以 乙醇 、 水 为溶剂， 生成 5-(P-甲氧基苯基)-5-甲基海因
  参考文献：
  名称：

  1,1-双三氟甲基甲醇衍生物作为肝X受体β选择性激动剂的设计、合成和药理学

  摘要：

  发现了一系列作为肝 X 受体 (LXR) β-选择性激动剂的新型 1,3-双三氟甲基甲醇衍生物。结构-活性关系研究导致分子62的鉴定，它比 T0901317 和 GW3965 对 LXRβ更有效 ( E max ) 和选择性。此外，在 Bio F 1中， 62降低了 LDL-C 而没有提高血浆 TG 水平，并显着抑制了主动脉弓中的脂质积聚区域B 仓鼠喂食高脂肪和高胆固醇的饮食。我们证明了我们的 LXRβ 激动剂可能用作降血脂和抗动脉粥样硬化剂。在这份手稿中，我们报告了 1,3-双三氟甲基甲醇衍生物的设计、合成和药理学。

  DOI：

  10.1016/j.bmcl.2015.04.080

文献信息

• Design and discovery of 2-oxochromene derivatives as liver X receptor β-selective agonists
  作者：Takayuki Matsuda、Ayumu Okuda、Yuichiro Watanabe、Tohru Miura、Hidefumi Ozawa、Ayako Tosaka、Koichi Yamazaki、Yuki Yamaguchi、Sayaka Kurobuchi、Minoru Koura、Kimiyuki Shibuya

  DOI：10.1016/j.bmcl.2015.01.047

  日期：2015.3

  an attempt to molecularly design liver X receptor (LXR) β-selective agonists, we discovered that the combination of the 2-oxochromene moiety (head) and the imidazoline-2,4-dione moiety (tail) plays an important role in the expression potency and selectivity toward LXRβ. We synthesized a series of 2-oxochromene derivatives and identified 43 as a LXRβ-selective agonist that increased the HDL-C level without

  在分子设计肝X受体（LXR）β-选择性激动剂的尝试中，我们发现2-氧代色烯部分（头部）和咪唑啉-2,4-二酮部分（尾巴）的组合在表达能力和对LXRβ的选择性。我们合成了一系列2-oxochromene衍生物，并确定了43种LXRβ选择性激动剂，可在不显着升高TG水平的情况下增加HDL-C水平，并导致高脂饮食中主动脉弓内脂质蓄积面积减少。和胆固醇喂养的Bio F 1 B仓鼠。在这份手稿中，我们报告了这些2-氧代苯并二氢吡喃衍生物的设计，合成和药理作用。
• CARBINOL DERIVATIVES HAVING CYCLIC LINKER
  申请人：Yamaguchi Yuki

  公开号：US20100048610A1

  公开（公告）日：2010-02-25

  [Object] To provide a novel LXRβ agonist that is useful as a preventative and/or therapeutic agent for atherosclerosis; arteriosclerosis such as those resulting from diabetes; dyslipidemia; hypercholesterolemia; lipid-related diseases; inflammatory diseases that are caused by inflammatory cytokines; skin diseases such as allergic skin diseases; diabetes; or Alzheimer's disease. [Solving Means] A carbinol compound represented by the following general formula (I) or salt thereof, or their solvate.

  提供一种新型的LXRβ激动剂，可用作预防和/或治疗动脉粥样硬化；动脉硬化，如糖尿病引起的动脉硬化；血脂异常；高胆固醇血症；与脂质相关的疾病；由炎性细胞因子引起的炎症性疾病；过敏性皮肤病；糖尿病；或阿尔茨海默病的治疗剂。【解决手段】以下一般式（I）所表示的羟甲基化合物或其盐，或其溶剂化合物。
• 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
• Solvent effects on the absorption spectra of potentially pharmacologically active 5-alkyl-5-arylhydantoins: A structure-property relationship study
  作者：Sleem Hmuda、Nebojsa Banjac、Nemanja Trisovic、Bojan Bozic、Natasa Valentic、Gordana Uscumlic

  DOI：10.2298/jsc120719118h

  日期：——

  To obtain an insight into the interactions of potential anticonvulsant drugs with their surrounding, two series of 5-methyl-5-aryl- and 5-ethyl-5-arylhydantoins were synthesized and their absorption spectra were recorded in the region from 200 to 400 nm in a set of selected solvents. The effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding interactions on the absorption maxima shifts were analyzed by means of the linear solvation energy relationship (LSER) concept of Kamlet and Taft. The ratio of the contributions of specific and nonspecific solvent-solute interactions were correlated with the corresponding ADME properties of the studied compounds. The correlation equations were combined with different physicochemical parameters to generate new equations, which demonstrate the reasonable relationships between solvent-solute interactions and the structure-activity parameters.

  为了深入了解潜在抗惊厥药物与周围环境的相互作用 的相互作用，合成了两个系列的 5-甲基-5-芳基和 5-乙基-5-芳基海因 合成了两个系列的 5-甲基-5-芳基和 5-乙基-5-芳基hydantoins，并在一组选定的溶剂中记录了它们在 200 至 400 纳米区域的吸收光谱。 在一组选定溶剂中记录了它们在 200 至 400 nm 波段的吸收光谱。溶剂的 溶剂的偶极性/极化性和溶剂-溶质氢键相互作用对吸收最大值偏移的影响。 通过线性溶解能关系分析了溶剂二极性/极化性和溶剂-溶剂氢键相互作用对吸收最大值移动的影响。 的线性溶解能关系（LSER）概念进行了分析。 塔夫脱的线性溶解能关系（LSER）概念进行了分析。特异性和非特异性 与所研究化合物相应的 ADME 相关。相关方程 与不同的理化参数相结合，生成了新的方程。 证明了溶剂-溶质相互作用与结构-活性参数之间的合理关系。 与结构-活性参数之间的合理关系。
• Catecholamine surrogates useful as .beta..sub.3 agonists
  申请人：Bristol-Myers Squibb Company

  公开号：US05770615A1

  公开（公告）日：1998-06-23

  Compounds of the formula ##STR1## and pharmaceutically acceptable salts thereof. These compounds are beta three adrenergic receptor agonists and are useful, therefore for example, in the treatment of diabetes, obesity and gastrointestinal diseases.

  公式为##STR1##的化合物及其药学上可接受的盐。这些化合物是β三肾上腺素受体激动剂，因此在糖尿病、肥胖症和胃肠疾病的治疗中是有用的。