5,5-dimethyl-3-[6-(trifluoromethyl)pyridin-3-yl]imidazolidine-2,4-dione

• 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: 5,5-dimethyl-3-[6-(trifluoromethyl)pyridin-3-yl]imidazolidine-2,4-dione
• 英文别名: 5,5-dimethyl-3-(6-trifluoromethylpyridin-3-yl)imidazolidine-2,4-dione
• 化学式: C₁₁H₁₀F₃N₃O₂
• 分子量: 273.215
• InChiKey: QWSFBCVNYCHVMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  62.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-碘-2-(三氟甲基)吡啶 、 5,5-二甲基海因 在 copper(I) oxide 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 48.0h， 以75%的产率得到5,5-dimethyl-3-[6-(trifluoromethyl)pyridin-3-yl]imidazolidine-2,4-dione
  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

文献信息

• Substituted imidazoline-2,4-diones, process for preparation thereof, medicaments comprising these compounds and use thereof
  申请人：Jaehne Gerhard

  公开号：US20110112097A1

  公开（公告）日：2011-05-12

  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具有所述含义，以及它们的生理相容盐。所述化合物适用于作为抗肥胖药物。
• SUBSTITUIERTE IMIDAZOLIDIN-2,4-DIONE, VERFAHREN ZU IHRER HERSTELLUNG, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL UND IHRE VERWENDUNG
  申请人：Sanofi-Aventis

  公开号：EP2242747A1

  公开（公告）日：2010-10-27
• [DE] SUBSTITUIERTE IMIDAZOLIDIN-2,4-DIONE, VERFAHREN ZU IHRER HERSTELLUNG, DIESE VERBINDUNGEN ENTHALTENDE ARZNEIMITTEL UND IHRE VERWENDUNG<br/>[EN] SUBSTITUTED IMIDAZOLIDINE-2,4-DIONES, METHOD FOR THE PRODUCTION THEREOF, MEDICAMENTS CONTAINING SAID COMPOUNDS AND USE THEREOF<br/>[FR] IMIDAZOLIDINE-2,4-DIONES SUBSTITUÉS, PROCÉDÉ DE PRODUCTION, MÉDICAMENTS CONTENANT CES COMPOSÉS ET LEUR UTILISATION
  申请人：SANOFI AVENTIS

  公开号：WO2009097997A1

  公开（公告）日：2009-08-13

  Die Erfindung betrifft Verbindungen der Formel (I) worin die Reste R und R', A, D, E, G, L, p und R1 bis R10 die angegebenen Bedeutungen haben, sowie deren physiologisch verträgliche Salze. Die Verbindungen eignen sich z.B. als Antiadiposita.
• Revisiting the SAR of the Antischistosomal Aryl Hydantoin (Ro 13-3978)
  作者：Chunkai Wang、Qingjie Zhao、Mireille Vargas、Jeremy O. Jones、Karen L. White、David M. Shackleford、Gong Chen、Jessica Saunders、Alice C. F. Ng、Francis C. K. Chiu、Yuxiang Dong、Susan A. Charman、Jennifer Keiser、Jonathan L. Vennerstrom

  DOI：10.1021/acs.jmedchem.6b01410

  日期：2016.12.8

  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.