3-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2,6-di-n-propylphenoxy)-butyl)-5-(4-(1-methylethoxy)phenyl)-5-methylimidazolidine-2,4-dione | 1031395-79-5

• 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: 3-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2,6-di-n-propylphenoxy)-butyl)-5-(4-(1-methylethoxy)phenyl)-5-methylimidazolidine-2,4-dione
• 英文别名: 3-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2,6-di-n-propylphenoxy)butyl)-5-(4-(1-methylethoxy)phenyl)-5-methylimidazolidine-2,4-dione；3-[4-[2,6-dipropyl-4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)phenyloxy]butyl]-5-methyl-5-[4-(1-methylethoxy)phenyl]imidazolidine-2,4-dione；3-[4-[2,6-Dipropyl-4-[1-hydroxy-1-(trifluoromethyl)-2,2,2-trifluoroethyl]phenoxy]butyl]-5-methyl-5-(4-isopropoxyphenyl)imidazolidine-2,4-dione；3-[4-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2,6-dipropylphenoxy]butyl]-5-methyl-5-(4-propan-2-yloxyphenyl)imidazolidine-2,4-dione
• CAS: 1031395-79-5
• 化学式: C₃₂H₄₀F₆N₂O₅
• 分子量: 646.67
• InChiKey: DFZLKVIVVZKYKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  45
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  88.1
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  3-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2,6-di-n-propylphenoxy)-butyl)-5-(4-(1-methylethoxy)phenyl)-5-methylimidazolidine-2,4-dione 在 CHIRALPAK AS-H column, 5 μm, 20 x 250 mm, flow rate: 1.0 mL/min 作用下， 以 乙醇 、 正己烷 为溶剂， 以99%的产率得到
  参考文献：
  名称：

  A practical synthesis for (S)-5-(4-(1-methylethoxy)phenyl)-5-methylimidazolidine-2,4-dione and its application in the synthesis of a novel liver X receptor β-selective agonist

  摘要：

  In this manuscript, the chiral separation of novel liver X receptor (LXR) beta-selective agonist (+/-)-1 revealed that (S)-5-(4-(1-methylethoxy)phenyl)-5-methylimidazolidine-2,4-dione (+)-2 was the essential moiety (tail) to express LXR beta-selective agonistic activity in a head-to-tail molecular design. The requisite configuration of (+)-2 was determined as the (S)-form by X-ray crystal structure analysis of (+)-halogenated 4. We obtained (S)-methyl 2-amino-2-(4-(1-methylethoxy)phenyl)propionate (+)-7 by resolution with L-mandelic acid and established a practical synthesis for (+)-2. 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2015.11.007
• 作为产物：
  描述：

  1-(4-异丙氧基苯基)乙酮 在 盐酸 、 potassium carbonate 作用下， 以 乙醇 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 3-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2,6-di-n-propylphenoxy)-butyl)-5-(4-(1-methylethoxy)phenyl)-5-methylimidazolidine-2,4-dione
  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

• SUBSTITUTED CARBINOL COMPOUND
  申请人：Kowa Company, Ltd.

  公开号：EP2098515B1

  公开（公告）日：2012-02-08
• US8168666B2
  申请人：——

  公开号：US8168666B2

  公开（公告）日：2012-05-01
• Design, synthesis and pharmacology of 1,1-bistrifluoromethylcarbinol derivatives as liver X receptor β-selective agonists
  作者：Minoru Koura、Takayuki Matsuda、Ayumu Okuda、Yuichiro Watanabe、Yuki Yamaguchi、Sayaka Kurobuchi、Yuuki Matsumoto、Kimiyuki Shibuya

  DOI：10.1016/j.bmcl.2015.04.080

  日期：2015.7

  A novel series of 1,3-bistrifluoromethylcarbinol derivatives that act as liver X receptor (LXR) β-selective agonists was discovered. Structure–activity relationship studies led to the identification of molecule 62, which was more effective (Emax) and selective toward LXRβ than T0901317 and GW3965. Furthermore, 62 decreased LDL-C without elevating the plasma TG level and significantly suppressed the

  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。
• A practical synthesis for (S)-5-(4-(1-methylethoxy)phenyl)-5-methylimidazolidine-2,4-dione and its application in the synthesis of a novel liver X receptor β-selective agonist
  作者：Minoru Koura、Hisashi Sumida、Yukiyoshi Yamazaki、Kimiyuki Shibuya

  DOI：10.1016/j.tetasy.2015.11.007

  日期：2016.1

  In this manuscript, the chiral separation of novel liver X receptor (LXR) beta-selective agonist (+/-)-1 revealed that (S)-5-(4-(1-methylethoxy)phenyl)-5-methylimidazolidine-2,4-dione (+)-2 was the essential moiety (tail) to express LXR beta-selective agonistic activity in a head-to-tail molecular design. The requisite configuration of (+)-2 was determined as the (S)-form by X-ray crystal structure analysis of (+)-halogenated 4. We obtained (S)-methyl 2-amino-2-(4-(1-methylethoxy)phenyl)propionate (+)-7 by resolution with L-mandelic acid and established a practical synthesis for (+)-2. 2015 Elsevier Ltd. All rights reserved.