(E)-4-methyl-1-(p-nitrophenyl)-1-penten-3-one | 86983-92-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-4-methyl-1-(p-nitrophenyl)-1-penten-3-one
• 英文别名: (E)-4-methyl-1-p-nitrophenylpent-1-en-3-one；4-methyl-1-(4-nitrophenyl)pent-1-ene-3-one；4-Methyl-1-(4-nitro-phenyl)-pent-1-en-3-one；(E)-4-methyl-1-(4-nitrophenyl)-1-penten-3-one；(E)-4-methyl-1-(4-nitrophenyl)pent-1-en-3-one
• CAS: 86983-92-8
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: KQYSDBJRUMAOHV-VMPITWQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  62.9
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-4-methyl-1-(p-nitrophenyl)-1-penten-3-one 在 palladium on activated charcoal 、 Pd-BaSO₄ 正丁基锂 、 (S)-(-)- α-甲基苄胺 、 氢气 、 二异丙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， -78.0~55.0 ℃ 、351.63 kPa 条件下， 反应 106.57h， 生成 (R)-3-hydroxy-3-[2-(4-tert-butoxycarbonylaminophenyl)ethyl]-4-methylpentanoic acid
  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：

  1-acetoxy-4-methyl-1-(p-nitrophenyl)pentan-3-one 在 吡啶 作用下， 以 甲基叔丁基醚 、 甲苯 为溶剂， 反应 6.0h， 生成 (E)-4-methyl-1-(p-nitrophenyl)-1-penten-3-one
  参考文献：
  名称：

  Schöpf 方法在 3-[2-(pN-Acetylaminophenyl)ethyl]-3-hydroxy-4-methylpentanoic 酸合成优化中的应用：同时还原三个官能团以最大化产率和通量

  摘要：

  应用 Schopf 方法开发高收率缩合工艺以制备不稳定的 β-(对硝基苯基)-α,β-不饱和酮体系，同时开发烯烃苄酯同时加氢/氢解的工艺，和硝基基团，允许构建廉价的途径获得 3-[2-(pN-乙酰氨基苯基)乙基]-3-羟基-4-甲基戊酸，这是制备 CI-1029 和相关 HIV 蛋白酶抑制剂的关键中间体。

  DOI：

  10.1021/op000206k

文献信息

• An Efficient and Stereoselective Synthesis of (<i>E</i>)-α-Enones via Arsonium Salts. Preparation of Key Intermediates for the Synthesis of Brassinosteroid and Prostaglandin
  作者：Yao-Zeng Huang、Li-Lan Shi、Sao-Wei Li

  DOI：10.1055/s-1988-27772

  日期：——

  (E)-1-Alkenyl alkyl ketones [(E)-α-Enones] are prepared in high yields and with high stereoselectivity by reaction of (2-oxoalkyl)triphenylarsonium bromides with aldehydes under solid-liquid phase-transfer conditions. Application of this methodology to the preparation of key intermediates for the synthesis of brassinosteroid and prostaglandin PGF2α is also reported.

  (E)-1-烯基烷基酮[(E)-α-烯酮]通过(2-氧代烷基)三苯基砷溴化物与醛在固-液相转移条件下反应制备，具有高产率和高立体选择性。本文还报道了将这种方法应用于制备植物激素油菜素内酯和前列腺素PGF2α的关键中间体。
• TRIPEPTIDE COMPOUND, PREPARATION METHOD THEREFOR, AND APPLICATION THEREOF
  申请人：NORTHWEST UNIVERSITY

  公开号：US20170267718A1

  公开（公告）日：2017-09-21

  Provided are a tripeptide compound, a preparation method therefor, and an application thereof. The structure of the related compound is represented by formula (I). The provided compound has angiotensin converting enzyme inhibiting bioactivity, and the compound and a pharmaceutical composition thereof play a role in preventing and treating hypertension and other cardiocerebral vascular system diseases.

  提供了一种三肽化合物，其制备方法和应用。相关化合物的结构由式（I）表示。提供的化合物具有抑制血管紧张素转换酶的生物活性，该化合物及其药物组成对预防和治疗高血压和其他心脑血管系统疾病起着作用。
• Methods of making dihydropyrone HIV protease inhibitors
  申请人：——

  公开号：US06380400B1

  公开（公告）日：2002-04-30

  The present invention relates to methods of making dihydropyrone HIV inhibitors.

  本发明涉及制备二氢吡喃类HIV抑制剂的方法。
• Barker, Steven D.; Norris, Robert K., Australian Journal of Chemistry, 1983, vol. 36, # 3, p. 527 - 544
  作者：Barker, Steven D.、Norris, Robert K.

  DOI：——

  日期：——
• BARKER, S. D.;NORRIS, R. K., AUSTRAL. J. CHEM., 1983, 36, N 3, 527-544
  作者：BARKER, S. D.、NORRIS, R. K.

  DOI：——

  日期：——