3-(4-benzyloxyphenyl)-N-methoxy-N-methyl-propionamide | 207737-63-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(4-benzyloxyphenyl)-N-methoxy-N-methyl-propionamide
• 英文别名: 3-(4-(benzyloxy)phenyl)-N-methoxy-N-methylpropanamide；3-(4-Benzyloxy-phenyl)-N-methoxy-N-methyl-propionamide；N-methoxy-N-methyl-3-(4-phenylmethoxyphenyl)propanamide
• CAS: 207737-63-1
• 化学式: C₁₈H₂₁NO₃
• 分子量: 299.37
• InChiKey: ZIBXETFNSPFTCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-benzyloxyphenyl)-N-methoxy-N-methyl-propionamide 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以85%的产率得到3-[4-(苄氧基)苯基]丙醛
  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 二氯甲烷 为溶剂， 反应 23.0h， 生成 3-(4-benzyloxyphenyl)-N-methoxy-N-methyl-propionamide
  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

• Unintended Formation of a 26-Membered Cycle in the Course of a Novel Approach to Myricanol, a Strained [7,0]-Metacyclophane
  作者：Paul Massé、Sabine Choppin、Lucia Chiummiento、Gilles Hanquet、Françoise Colobert

  DOI：10.1055/s-0039-1691523

  日期：2020.4

  diarylheptanoid isolated from Myricacae, was undertaken using a Suzuki–Miyaura coupling followed by a ring-closing metathesis (RCM). Herein, we report the unintentional formation of a 26-membered macrocycle as RCM product resulting from a head-to-tail dimerization of the seco-precursor, even in relay ring-closing metathesis (RRCM) conditions.

  使用 Suzuki-Miyaura 偶联和闭环复分解 (RCM) 进行合成 (±)-杨梅醇（一种从杨梅科分离的应变二芳基庚烷）的收敛方法。在这里，我们报告了 26 元大环作为 RCM 产物的无意形成，这是由二元前体的头对尾二聚化产生的，即使在中继闭环复分解 (RRCM) 条件下也是如此。
• 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。
• DIHYDROPYRONES WITH IMPROVED ANTIVIRAL ACTIVITY
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0935597A2

  公开（公告）日：1999-08-18
• US5834506A
  申请人：——

  公开号：US5834506A

  公开（公告）日：1998-11-10
• US6046355A
  申请人：——

  公开号：US6046355A

  公开（公告）日：2000-04-04