4-benzyloxyphenethyl n-butyl ketone | 207736-75-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-benzyloxyphenethyl n-butyl ketone
• 英文别名: 1-(4-Benzyloxyphenyl)-heptan-3-one；1-(4-phenylmethoxyphenyl)heptan-3-one
• CAS: 207736-75-2
• 化学式: C₂₀H₂₄O₂
• 分子量: 296.409
• InChiKey: PPXZIRCPQGPVHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-benzyloxyphenethyl n-butyl ketone 在 palladium on activated charcoal 正丁基锂 、 氢气 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 生成 2-butyl-5-[2-tert-butyl-4-(2-hydroxyethoxy)-5-methyl-phenyl]sulfanyl-4-hydroxy-2-[2-(4-hydroxyphenyl)ethyl]-3H-pyran-6-one
  参考文献：
  名称：

  Nonpeptidic HIV protease inhibitors possessing excellent antiviral activities and therapeutic indices. PD 178390: a lead HIV protease inhibitor

  摘要：

  With the insight generated by the availability of X-ray crystal structures of various 5,6-dihydropyran-2-ones bound to HIV PR, inhibitors possessing various alkyl groups at the 6-position of 5,6-dihydropyran-2-one ring were synthesized. The inhibitors possessing a 6-alkyl group exhibited superior antiviral activities when compared to 6-phenyl analogues. Antiviral efficacies were further improved upon introduction of a polar group (hydroxyl or amino) on the 4-position of the phenethyl moiety as well as the polar group (hydroxymethyl) on the 3-(tert-butyl-5-methyl-phenylthio) moiety. The polar substitution is also advantageous for decreasing toxicity, providing inhibitors with higher therapeutic indices. The best inhibitor among this series, (S)-6-[2-(4-aminophenyl)-ethyl]-(3-(2-tert-butyl-5-methyl-phenylsulfa nyl)-4-hydroxy-6-isopropyl-5,6-dihydro-pyran-2-one (34S), exhibited an EC50 of 200 nM with a therapeutic index of > 1000. More importantly, these non-peptidic inhibitors, 16S and 34S, appear to offer little cross-resistance to the currently marketed peptidomimetic PR inhibitors. The selected inhibitors tested in vitro against mutant HIV PR showed a very small increase in binding affinities relative to wild-type HIV PR. Cmax and absolute bioavailability of 34S were higher and half-life and time above EC95 were longer compared to 16S. Thus 34S, also known as PD 178390, which displays good antiviral efficacy, promising pharmacokinetic characteristics and favorable activity against mutant enzymes and CYP3A4, has been chosen for further preclinical evaluation.

  DOI：

  10.1016/s0968-0896(99)00215-1
• 作为产物：
  描述：

  3-[4-(苄氧基)苯基]丙酸 在 吡啶 、 氯化亚砜 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 39.0h， 生成 4-benzyloxyphenethyl n-butyl ketone
  参考文献：
  名称：

  Nonpeptidic HIV protease inhibitors possessing excellent antiviral activities and therapeutic indices. PD 178390: a lead HIV protease inhibitor

  摘要：

  With the insight generated by the availability of X-ray crystal structures of various 5,6-dihydropyran-2-ones bound to HIV PR, inhibitors possessing various alkyl groups at the 6-position of 5,6-dihydropyran-2-one ring were synthesized. The inhibitors possessing a 6-alkyl group exhibited superior antiviral activities when compared to 6-phenyl analogues. Antiviral efficacies were further improved upon introduction of a polar group (hydroxyl or amino) on the 4-position of the phenethyl moiety as well as the polar group (hydroxymethyl) on the 3-(tert-butyl-5-methyl-phenylthio) moiety. The polar substitution is also advantageous for decreasing toxicity, providing inhibitors with higher therapeutic indices. The best inhibitor among this series, (S)-6-[2-(4-aminophenyl)-ethyl]-(3-(2-tert-butyl-5-methyl-phenylsulfa nyl)-4-hydroxy-6-isopropyl-5,6-dihydro-pyran-2-one (34S), exhibited an EC50 of 200 nM with a therapeutic index of > 1000. More importantly, these non-peptidic inhibitors, 16S and 34S, appear to offer little cross-resistance to the currently marketed peptidomimetic PR inhibitors. The selected inhibitors tested in vitro against mutant HIV PR showed a very small increase in binding affinities relative to wild-type HIV PR. Cmax and absolute bioavailability of 34S were higher and half-life and time above EC95 were longer compared to 16S. Thus 34S, also known as PD 178390, which displays good antiviral efficacy, promising pharmacokinetic characteristics and favorable activity against mutant enzymes and CYP3A4, has been chosen for further preclinical evaluation.

  DOI：

  10.1016/s0968-0896(99)00215-1

文献信息

• Dihydropyrones with improved antiviral activity
  申请人：Warner-Lambert Company

  公开号：US06046355A1

  公开（公告）日：2000-04-04

  This invention pertains to improved antiviral activity of 6,6-disubstituted-5,6-dihydropyran-2-ones caused by judicious placement of certain polar substituents at the 3 and/or 6 positions. The same substituents which enhance the cellular activity also diminish cytotoxicity further enhancing the desirable properties of these agents as antivirals.

  本发明涉及通过在3和/或6位恰当地放置某些极性取代基，改善6,6-二取代-5,6-二氢吡喃-2-酮的抗病毒活性。这些增强细胞活性的相同取代基还降低了细胞毒性，进一步增强了这些化合物作为抗病毒药物的理想性能。
• Optically active ester derivatives, preparation process thereof, liquid crystal materials and a light switching element
  申请人：SUMITOMO CHEMICAL COMPANY, LIMITED

  公开号：EP0357372A2

  公开（公告）日：1990-03-07

  Disclosed are herein optically active ester derivatives represented by the formula (I): (wherein R1 represents an alkyl group having 3 to 20 carbon atoms; R2 represents an optically active alkyl or alkoxyalkyl group having 3 to 15 carbon atoms optionally substituted by halogen atoms; Y represents -O-, -COO- or -OCO-; X represents -COO- or -OCO-; represents a number of 1 or 2; k and m each represents a number of 0 or 1; n represents a numberof 1 to 6), preparation processes therefor, liquid crystal materials containing such easter derivatives as active ingredient, and a light switching element using said liquid crystal materials as liquid crystal element.

  本文公开了由式(I)代表的光学活性酯衍生物： (其中 R1 代表具有 3 至 20 个碳原子的烷基；R2 代表具有 3 至 15 个碳原子的光学活性烷基或烷氧基烷基，可选择被卤素原子取代；Y 代表 -O-、-COO- 或 -OCO-；X 代表 -COO- 或 -OCO-；代表 1 或 2 的数字；k 和 m 分别代表 0 或 1 的数字；n 代表 1 至 6 的数字）、其制备工艺、含有此类酯衍生物作为活性成分的液晶材料，以及使用上述液晶材料作为液晶元件的光开关元件。
• DIHYDROPYRONES WITH IMPROVED ANTIVIRAL ACTIVITY
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0935597A2

  公开（公告）日：1999-08-18
• US5124070A
  申请人：——

  公开号：US5124070A

  公开（公告）日：1992-06-23
• US5264151A
  申请人：——

  公开号：US5264151A

  公开（公告）日：1993-11-23