5,5-二甲基-3-(alpha,alpha,alpha,4-四氟-3-甲苯基)海因 | 70842-04-5

• 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: 5,5-二甲基-3-(alpha,alpha,alpha,4-四氟-3-甲苯基)海因
• 英文名称: Ro 13-3978
• 英文别名: 3-(4-Fluoro-3-(trifluoromethyl)phenyl)-5,5-dimethylimidazolidine-2,4-dione；3-[4-fluoro-3-(trifluoromethyl)phenyl]-5,5-dimethylimidazolidine-2,4-dione
• CAS: 70842-04-5
• 化学式: C₁₂H₁₀F₄N₂O₂
• 分子量: 290.217
• InChiKey: BTGSGTWRNQCEQY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5,5-二甲基-3-(alpha,alpha,alpha,4-四氟-3-甲苯基)海因 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 4.0h， 以95%的产率得到2-[3-[4-fluoro-3-(trifluoromethyl)phenyl]ureido]-2-methylpropanoic acid
  参考文献：
  名称：

  Revisiting the SAR of the Antischistosomal Aryl Hydantoin (Ro 13-3978)

  摘要：

  The aryl hydantoin 1 (Ro 13-3978) was identified in the early 1980s as a promising antischistosomal lead compound. However, this series of aryl hydantoins produced antiandrogenic side effects in the host, a not unexpected outcome given their close structural similarity to the antiandrogenic drug nilutamide. Building on the known SAR of this compound series, we now describe a number of analogs of 1 designed to maximize structural diversity guided by incorporation of substructures and functional groups known to diminish ligand-androgen receptor interactions. These analogs had calculated polar surface area (PSA), measured LogD(7.4), aqueous kinetic solubility, and estimated plasma protein binding values in ranges predictive of good ADME profiles. The principal SAR insight was that the hydantoin core of 1 is required for high antischistosomal activity. We identified several compounds with high antischistosomal efficacy that were less antiandrogenic than 1. These data provide direction for the ongoing optimization of antischistosomal hydantoins.

  DOI：

  10.1021/acs.jmedchem.6b01410
• 作为产物：
  描述：

  4-氟-3-三氟甲基苯胺 在 盐酸 作用下， 以 丙酮 为溶剂， 生成 5,5-二甲基-3-(alpha,alpha,alpha,4-四氟-3-甲苯基)海因
  参考文献：
  名称：

  Link; Stohler, European Journal of Medicinal Chemistry, 1984, vol. 19, # 3, p. 261 - 265

  摘要：

  DOI：

文献信息

• Novel phenyl-substituted imidazolidines, process for preparation thereof, medicaments comprising said compounds and use thereof
  申请人：JAEHNE Gerhard

  公开号：US20110178134A1

  公开（公告）日：2011-07-21

  The invention relates to compounds of formula (I) wherein the groups have stated meanings, and to their physiologically compatible salts. Said compounds are suitable, for example, as anti-obesity drugs and for treating cardiometabolic syndrome.

  本发明涉及具有所述意义的公式（I）的化合物，以及它们的生理相容性盐。所述化合物适用于例如作为抗肥胖药物和治疗心血管代谢综合征。
• Arylchalcogenoarylalkyl-substituted imidazolidine-2,4-diones, process for preparation thereof, medicaments comprising these compounds and use thereof
  申请人：JAEHNE Gerhard

  公开号：US20110053947A1

  公开（公告）日：2011-03-03

  The invention relates to compounds of formula (I) wherein the groups R and R′, A, D, E, G, L, p and R1 to R10 have the stated meanings and to their physiologically compatible salts. Said compounds are suitable, for example, as anti-obesity drugs.

  本发明涉及具有公式（I）的化合物，其中R和R'、A、D、E、G、L、p以及R1至R10具有所述含义，以及它们的生理相容性盐。所述化合物例如可作为抗肥胖药物使用。
• Arylaminoaryl-alkyl-substituted imidazolidine-2,4-diones, process for preparing them, medicaments comprising these compounds, and their use
  申请人：JAEHNE Gerhard

  公开号：US20090215728A1

  公开（公告）日：2009-08-27

  This invention relates to arylaminoaryl-alkyl-substituted imidazolidone-2,4-diones of formula (I) and also to their physiologically tolerated salts: Wherein R, R′, R1 to R10, A, D, E, G, L and p are as defined herein. The invention also relates to processes for preparing them, pharmaceutical compositions comprising them and their therapeutic use. The compounds are suitable, for example, as anti-obesity drugs and for treating cardiometabolic syndrome.

  这项发明涉及公式（I）中的芳基氨基芳基烷基取代的咪唑烷二酮及其生理耐受的盐： 其中R、R'、R1至R10、A、D、E、G、L和p如本文所定义。该发明还涉及制备它们的方法、包含它们的药物组合物以及它们的治疗用途。这些化合物适用于例如作为抗肥胖药物和治疗心脏代谢综合征。
• Heterocycle-substituted imidazolidine-2,4-diones, process for preparation thereof, medicaments comprising them and use thereof
  申请人：Jaehne Gerhard

  公开号：US20110046105A1

  公开（公告）日：2011-02-24

  The invention relates to compounds of formula (I) wherein the groups R and R′, A, D, E, G, L, p and R1 to R10 have the stated meanings and to their physiologically compatible salts. Said compounds are suitable, for example, as anti-obesity drugs.

  该发明涉及式(I)的化合物，其中基团R和R'、A、D、E、G、L、p以及R1到R10具有所述的含义，以及它们的生理兼容盐。所述化合物可作为抗肥胖药物，例如。
• SAR of a new antischistosomal urea carboxylic acid
  作者：Jianbo Wu、Chunkai Wang、Cécile Häberli、Karen L. White、David M. Shackleford、Gong Chen、Yuxiang Dong、Susan A. Charman、Jennifer Keiser、Jonathan L. Vennerstrom

  DOI：10.1016/j.bmcl.2018.10.039

  日期：2018.12

  Urea carboxylic acids, products of aryl hydantoin hydrolysis, were recently identified as a new antischistosomal chemotype. We now describe a baseline structure-activity relationship (SAR) for this compound series. With one exception, analogs of lead urea carboxylic acid 2 were quite polar with Log D7.4 values ranging from -1.9 to 1.8, had high aqueous solubilities in the range of 25-100 µg/mL, and

  尿素羧酸，芳基乙内酰脲水解产物，最近被确定为一种新的抗血吸虫化学型。现在我们描述该化合物系列的基线结构-活性关系（SAR）。除一个例外，尿素羧酸铅2的类似物具有极高的极性，对数D7.4值在-1.9至1.8范围内，在25-100 µg / mL的范围内具有较高的水溶解度，并且在代谢上稳定。这些化合物均无可测量的体外抗血吸虫病活性或细胞毒性，但是当以100 mg / kg的单剂量口服剂量对曼氏沙门氏菌感染的小鼠给药时，其中四种化合物具有中等的蠕虫减负（WBR）值，为42-70％。 。这些数据表明，除了宝石二甲基亚结构和尿素官能团的远端氮原子外，