(3-Chlorophenyl)(quinolin-4-yl)methanol | 161218-42-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (3-Chlorophenyl)(quinolin-4-yl)methanol
• 英文别名: (3-chlorophenyl)-quinolin-4-ylmethanol
• CAS: 161218-42-4
• 化学式: C₁₆H₁₂ClNO
• 分子量: 269.73
• InChiKey: XIDRYHMVOGSUHQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  33.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (3-Chlorophenyl)(quinolin-4-yl)methanol 在 N,N-二甲基甲酰胺 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 3.83h， 生成
  参考文献：
  名称：

  Clotrimazole Scaffold as an Innovative Pharmacophore Towards Potent Antimalarial Agents: Design, Synthesis, and Biological and Structure–Activity Relationship Studies

  摘要：

  We describe herein the design, synthesis, biological evaluation, and structure-activity relationship (SAR) studies of an innovative class of antimalarial agents based on a polyaromatic pharmacophore structurally related to clotrimazole and easy to synthesize by low-cost synthetic procedures. SAR studies delineated a number of structural features able to modulate the in vitro and in vivo antimalarial activity. A selected set of antimalarials was further biologically investigated and displayed low in vitro toxicity on a panel of human and murine cell lines. In vitro, the novel compounds proved to be selective for free heme, as demonstrated in the beta-hematin inhibitory activity assay, and did not show inhibitory activity against 14-alpha-lanosterol demethylase (a fungal P450 cytochrome). Compounds 2, 4e, and 4n exhibited in vivo activity against P. chabaudi after oral administration and thus represent promising antimalarial agents for further preclinical development.

  DOI：

  10.1021/jm701247k
• 作为产物：
  描述：

  4-喹啉甲醛 、 (3-chlorophenyl)magnesium bromide 以 四氢呋喃 为溶剂， 反应 6.0h， 以48%的产率得到(3-Chlorophenyl)(quinolin-4-yl)methanol
  参考文献：
  名称：

  Clotrimazole Scaffold as an Innovative Pharmacophore Towards Potent Antimalarial Agents: Design, Synthesis, and Biological and Structure–Activity Relationship Studies

  摘要：

  We describe herein the design, synthesis, biological evaluation, and structure-activity relationship (SAR) studies of an innovative class of antimalarial agents based on a polyaromatic pharmacophore structurally related to clotrimazole and easy to synthesize by low-cost synthetic procedures. SAR studies delineated a number of structural features able to modulate the in vitro and in vivo antimalarial activity. A selected set of antimalarials was further biologically investigated and displayed low in vitro toxicity on a panel of human and murine cell lines. In vitro, the novel compounds proved to be selective for free heme, as demonstrated in the beta-hematin inhibitory activity assay, and did not show inhibitory activity against 14-alpha-lanosterol demethylase (a fungal P450 cytochrome). Compounds 2, 4e, and 4n exhibited in vivo activity against P. chabaudi after oral administration and thus represent promising antimalarial agents for further preclinical development.

  DOI：

  10.1021/jm701247k

文献信息

• Clotrimazole Scaffold as an Innovative Pharmacophore Towards Potent Antimalarial Agents: Design, Synthesis, and Biological and Structure–Activity Relationship Studies
  作者：Sandra Gemma、Giuseppe Campiani、Stefania Butini、Gagan Kukreja、Salvatore Sanna Coccone、Bhupendra P. Joshi、Marco Persico、Vito Nacci、Isabella Fiorini、Ettore Novellino、Ernesto Fattorusso、Orazio Taglialatela-Scafati、Luisa Savini、Donatella Taramelli、Nicoletta Basilico、Silvia Parapini、Giulia Morace、Vanessa Yardley、Simon Croft、Massimiliano Coletta、Stefano Marini、Caterina Fattorusso

  DOI：10.1021/jm701247k

  日期：2008.3.13

  We describe herein the design, synthesis, biological evaluation, and structure-activity relationship (SAR) studies of an innovative class of antimalarial agents based on a polyaromatic pharmacophore structurally related to clotrimazole and easy to synthesize by low-cost synthetic procedures. SAR studies delineated a number of structural features able to modulate the in vitro and in vivo antimalarial activity. A selected set of antimalarials was further biologically investigated and displayed low in vitro toxicity on a panel of human and murine cell lines. In vitro, the novel compounds proved to be selective for free heme, as demonstrated in the beta-hematin inhibitory activity assay, and did not show inhibitory activity against 14-alpha-lanosterol demethylase (a fungal P450 cytochrome). Compounds 2, 4e, and 4n exhibited in vivo activity against P. chabaudi after oral administration and thus represent promising antimalarial agents for further preclinical development.