4-Methyl-1-pyridin-4-yl-pentan-3-one | 261711-17-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 4-Methyl-1-pyridin-4-yl-pentan-3-one
• 英文别名: 4-methyl-1-pyridin-4-ylpentan-3-one
• CAS: 261711-17-5
• 化学式: C₁₁H₁₅NO
• 分子量: 177.246
• InChiKey: GWTUBOLDBGWWJZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-Methyl-1-pyridin-4-yl-pentan-3-one 在 sodium hydroxide 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.33h， 生成 3-(2-tert-Butyl-4-hydroxymethyl-5-methyl-phenylsulfanyl)-4-hydroxy-6-isopropyl-6-(2-pyridin-4-yl-ethyl)-5,6-dihydro-pyran-2-one
  参考文献：
  名称：

  4-Hydroxy-5,6-dihydropyrones as Inhibitors of HIV Protease:  The Effect of Heterocyclic Substituents at C-6 on Antiviral Potency and Pharmacokinetic Parameters

  摘要：

  Due largely to the emergence of multi-drug-resistant HIV strains, the development of new HIV protease inhibitors remains a high priority for the pharmaceutical industry. Toward this end, we previously identified a 4-hydroxy-5,6-dihydropyrone lead compound (CI-1029, 1) which possesses excellent activity against the protease enzyme, good antiviral efficacy in cellular assays, and promising bioavailability in several animal species. The search for a suitable backup candidate centered on the replacement of the aniline moiety at C-6 with an appropriately substituted heterocyle. In general, this series of heterocyclic inhibitors displayed good activity (in both enzymatic and cellular tests) and-low cellular toxicity; furthermore, several analogues exhibited improved pharmacokinetic parameters in animal models. The compound with the best combination of high potency, low toxicity, and favorable bioavailabilty was (S)-3-(2-tertbutyl-4-hydroxymethy1- 5-methyl-phenylsulfanyl)-4-hydroxy-6-isopropyl-6-(2-thiophen-3-yl-ethyl)-5,6-dihydro-pyran-2-one (13-(S)). This thiophene derivative also exhibited excellent antiviral efficacy against mutant HIV protease and resistant HIV strains. For these reasons, compound 13-(S) was chosen for further preclinical evaluation.

  DOI：

  10.1021/jm0003844
• 作为产物：
  描述：

  3-methyl-2-oxobutyl-triphenyl arsonium bromide 在 5percent Pd/BaSO₄ 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 、 乙腈 为溶剂， 20.0 ℃ 、220.64 kPa 条件下， 反应 44.0h， 生成 4-Methyl-1-pyridin-4-yl-pentan-3-one
  参考文献：
  名称：

  4-Hydroxy-5,6-dihydropyrones as Inhibitors of HIV Protease:  The Effect of Heterocyclic Substituents at C-6 on Antiviral Potency and Pharmacokinetic Parameters

  摘要：

  Due largely to the emergence of multi-drug-resistant HIV strains, the development of new HIV protease inhibitors remains a high priority for the pharmaceutical industry. Toward this end, we previously identified a 4-hydroxy-5,6-dihydropyrone lead compound (CI-1029, 1) which possesses excellent activity against the protease enzyme, good antiviral efficacy in cellular assays, and promising bioavailability in several animal species. The search for a suitable backup candidate centered on the replacement of the aniline moiety at C-6 with an appropriately substituted heterocyle. In general, this series of heterocyclic inhibitors displayed good activity (in both enzymatic and cellular tests) and-low cellular toxicity; furthermore, several analogues exhibited improved pharmacokinetic parameters in animal models. The compound with the best combination of high potency, low toxicity, and favorable bioavailabilty was (S)-3-(2-tertbutyl-4-hydroxymethy1- 5-methyl-phenylsulfanyl)-4-hydroxy-6-isopropyl-6-(2-thiophen-3-yl-ethyl)-5,6-dihydro-pyran-2-one (13-(S)). This thiophene derivative also exhibited excellent antiviral efficacy against mutant HIV protease and resistant HIV strains. For these reasons, compound 13-(S) was chosen for further preclinical evaluation.

  DOI：

  10.1021/jm0003844
• 作为试剂：
  描述：

  4-Methyl-1-pyridin-4-yl-pent-1-en-3-one 、 在 4-Methyl-1-pyridin-4-yl-pentan-3-one 作用下， 以 四氢呋喃 为溶剂， 生成 4-Methyl-1-pyridin-4-yl-pentan-3-one
  参考文献：
  名称：

  HIV protease inhibitors

  摘要：

  本发明涉及新型带有异构环的链式二氢吡喃，具有改良的药理学性质，能够强力抑制HIV天冬氨酸蛋白酶，从而阻止HIV的感染性。这些二氢吡喃可用于开发治疗病毒感染和疾病的疗法，包括艾滋病。本发明还涉及制备这些二氢吡喃的合成方法和制备最终化合物的中间体。

  公开号：

  US20050075390A1

文献信息

• MCL-1 INHIBITORS
  申请人：Gilead Sciences, Inc.

  公开号：US20190352271A1

  公开（公告）日：2019-11-21

  The present disclosure generally relates to compounds and pharmaceutical compositions that may be used in methods of treating cancer.

  本公开涉及通常用于治疗癌症的化合物和药物组合物。
• MCL-1 inhibitors
  申请人：Gilead Sciences, Inc.

  公开号：US10703733B2

  公开（公告）日：2020-07-07

  The present disclosure generally relates to compounds and pharmaceutical compositions that may be used in methods of treating cancer.

  本公开内容一般涉及可用于治疗癌症方法的化合物和药物组合物。
• HIV PROTEASE INHIBITORS
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP1112269A2

  公开（公告）日：2001-07-04
• SUBSTITUTED AZASPIRO(4.5)DECANE DERIVATIVES
  申请人：Grünenthal GmbH

  公开号：EP3169666B1

  公开（公告）日：2018-06-06
• US6528510B1
  申请人：——

  公开号：US6528510B1

  公开（公告）日：2003-03-04