4-(2,6-difluorophenyl)cyclohexan-1-one | 1081110-87-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(2,6-difluorophenyl)cyclohexan-1-one
• 英文别名: 4-(2,6-difluorophenyl)cyclohexanone
• CAS: 1081110-87-3
• 化学式: C₁₂H₁₂F₂O
• 分子量: 210.223
• InChiKey: UPLLXUMYJQUUET-UHFFFAOYSA-N

物化性质

• 沸点：
  253.4±40.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  17.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2,6-difluorophenyl)cyclohexan-1-one 在 tris-(dibenzylideneacetone)dipalladium(0) 、 L-Selectride 、 sodium hydride 、 caesium carbonate 、 2-二-叔丁膦基-2',4',6'-三异丙基联苯 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 mineral oil 为溶剂， 反应 11.08h， 生成 N-(2-(((cis-4-(2,6-difluorophenyl)cyclohexyl)oxy)methyl)pyridin-3-yl)methanesulfonamide
  参考文献：
  名称：

  [EN] SUBSTITUTED PIPERIDINE COMPOUND AND USE THEREOF
  [FR] COMPOSÉ DE PIPÉRIDINE SUBSTITUÉE ET SON UTILISATION

  摘要：

  提供的是一种替代哌啶化合物，具有促进俐克脑肽2型受体激动剂活性。公式（I）所代表的化合物：其中每个符号如描述中所述，或其盐具有促进俐克脑肽2型受体激动剂活性，并且可用作嗜睡症的预防或治疗药物。

  公开号：

  WO2017135306A1
• 作为产物：
  描述：

  4-(2,6-Difluorophenyl)cyclohex-3-en-1-one 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙酸乙酯 为溶剂， 20.0 ℃ 、500.01 kPa 条件下， 反应 20.0h， 生成 4-(2,6-difluorophenyl)cyclohexan-1-one
  参考文献：
  名称：

  Novel 4-(4-Aryl)cyclohexyl-1-(2-pyridyl)piperazines as Δ₈−Δ₇ Sterol Isomerase (Emopamil Binding Protein) Selective Ligands with Antiproliferative Activity

  摘要：

  To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some a receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH3, CH3O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-pyridyl)piperazines was developed. Radioreceptor binding assays evidenced cis-19, cis-30 and cis-33 as new ligands with nanomolar affinity toward EBP site and a good selectivity relative to EBP-related a receptors. The most selective 2,6-dimethoxy derivative (cis-33) demonstrated the highest potency (EC50 = 12.9 mu M) and efficacy (70%) in inhibiting proliferation of human prostate cancer PC-3 cell line. Among the reference compounds, sigma(2) agonist 36 (PB28) reached the maximum efficacy (100%), suggesting the contribution of the sigma(2) receptor to the antiproliferative activity, This novel class of EBP inhibitors represents a valuable tool for investigating the last steps of cholesterol biosynthesis and related pathologies, as well its a starting point for developing new anticancer drugs.

  DOI：

  10.1021/jm800965b

文献信息

• 1-Cyclohexyl-4-(4-arylcyclohexyl)piperazines: Mixed σ and Human Δ8-Δ7 Sterol Isomerase Ligands with Antiproliferative and P-Glycoprotein Inhibitory Activity
  作者：Carmen Abate、Mauro Niso、Marialessandra Contino、Nicola Antonio Colabufo、Savina Ferorelli、Roberto Perrone、Francesco Berardi

  DOI：10.1002/cmdc.201000371

  日期：2011.1.3

  designed as mixed affinity ligands for sigma (σ) receptors and human Δ8–Δ7 sterol isomerase (HSI) ligands, which also exhibit P‐glycoprotein (P‐gp) inhibitory activity, with the aim of exploiting the antiproliferative effects mediated by σ and HSI sites while overcoming P‐gp‐mediated resistance. All of the compounds displayed high affinities for σ receptors and HSI sites, P‐gp inhibitory activity, and σ2

  许多新的化学治疗剂正在临床前研究中，尽管努力更选择性地靶向癌细胞，但经常遇到诸如毒性和固有耐药性的局限性。因此，需要替代策略来治疗癌症并克服这种局限性。我们描述了新颖的环己基衍生物，设计为混合亲和配体对σ（σ）受体和人类Δ 8 -Δ 7固醇异构酶（HSI）配体，其也表现出P-糖蛋白（P-gp）的抑制活性，与利用的目的由σ和HSI位点介导的抗增殖作用，同时克服了P-gp介导的耐药性。所有的化合物都显示出对σ受体和HSI位点，P-gp的抑制活性高的亲和力，和σ 2受体激动剂的抗增殖活性。抗增殖活性也在PC-3细胞测试，以建立σ 1和HSI贡献。化合物顺式- 11，其显示最佳抗增殖和P-gp的抑制活性，用0.1μ共同施用中号在MDCK-MDR1细胞的阿霉素。化合物顺式- 11引起70％和90％的细胞死亡共同施用时，在30μ中号和50μ米，分别。单独使用时，cis - 11导致50％的细胞死亡，这
• [EN] SUBSTITUTED PIPERIDINE COMPOUND AND USE THEREOF<br/>[FR] COMPOSÉ DE PIPÉRIDINE SUBSTITUÉE ET SON UTILISATION
  申请人：TAKEDA PHARMACEUTICALS CO

  公开号：WO2017135306A1

  公开（公告）日：2017-08-10

  Provided is a substituted piperidine compound having an orexin type 2 receptor agonist activity. A compound represented by the formula (I): wherein each symbol is as described in the DESCRIPTION, or a salt thereof has an orexin type 2 receptor agonist activity, and is useful as a prophylactic or therapeutic agent for narcolepsy.

  提供的是一种替代哌啶化合物，具有促进俐克脑肽2型受体激动剂活性。公式（I）所代表的化合物：其中每个符号如描述中所述，或其盐具有促进俐克脑肽2型受体激动剂活性，并且可用作嗜睡症的预防或治疗药物。
• Novel 4-(4-Aryl)cyclohexyl-1-(2-pyridyl)piperazines as Δ₈−Δ₇ Sterol Isomerase (Emopamil Binding Protein) Selective Ligands with Antiproliferative Activity
  作者：Francesco Berardi、Carmen Abate、Savina Ferorelli、Anna F. de Robertis、Marcello Leopoldo、Nicola A. Colabufo、Mauro Niso、Roberto Perrone

  DOI：10.1021/jm800965b

  日期：2008.12.11

  To find Delta(8)-Delta(7) sterol isomerase (EBP) selective ligands, various arylpiperazines previously studied and structurally related to some a receptors ligands were preliminarily screened. Consequently, a novel series of 2- or 2,6-disubstituted (CH3, CH3O, Cl, F) cis- and trans-4-(4-aryl)cyclohexyl-1-(2-pyridyl)piperazines was developed. Radioreceptor binding assays evidenced cis-19, cis-30 and cis-33 as new ligands with nanomolar affinity toward EBP site and a good selectivity relative to EBP-related a receptors. The most selective 2,6-dimethoxy derivative (cis-33) demonstrated the highest potency (EC50 = 12.9 mu M) and efficacy (70%) in inhibiting proliferation of human prostate cancer PC-3 cell line. Among the reference compounds, sigma(2) agonist 36 (PB28) reached the maximum efficacy (100%), suggesting the contribution of the sigma(2) receptor to the antiproliferative activity, This novel class of EBP inhibitors represents a valuable tool for investigating the last steps of cholesterol biosynthesis and related pathologies, as well its a starting point for developing new anticancer drugs.