(7-chloroquinolin-4-yl)(4-fluorophenyl)methanone | 169957-16-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (7-chloroquinolin-4-yl)(4-fluorophenyl)methanone
• 英文别名: (7-Chloroquinolin-4-yl)-(4-fluorophenyl)methanone
• CAS: 169957-16-8
• 化学式: C₁₆H₉ClFNO
• 分子量: 285.705
• InChiKey: LTCQJNLRHWPOLD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  30
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-溴苯甲基)吡咯烷 、 (7-chloroquinolin-4-yl)(4-fluorophenyl)methanone 在 碘 magnesium 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以40%的产率得到(4-氟苯基)[4-(吡咯烷-1-基甲基)苯基](7-氯喹啉-4-基)甲醇
  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：

  2-(7-chloroquinolin-4-yl)-2-(4-fluorophenyl)acetonitrile 在 氧气 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以90%的产率得到(7-chloroquinolin-4-yl)(4-fluorophenyl)methanone
  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

• [EN] ANTIMALARIAL AGENTS HAVING POLYAROMATIC STRUCTURE<br/>[FR] AGENTS ANTIMALARIAUX DE STRUCTURE POLYAROMATIQUE
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2007104696A1

  公开（公告）日：2007-09-20

  [EN] Antimalarial agents having a novel pharmacophore of formula (I) are herein described. These polycyclic compounds are able to inhibit chloroquine-sensitive and chloroquine-resistant strains ofPlasmodium falciparum (Pf). Furthermore, the synthesis of these compounds involves few steps from commercial products with low cost of production.
  [FR] La présente invention concerne des agents antimalariaux comportant un nouveau pharmacophore de formule (I). Ces composés polycycliques sont susceptibles d'inhiber les souches sensibles à la chloroquine et résistantes à la chloroquine de Plasmodium falciparum (Pf). En outre, la synthèse de ces composés est peu onéreuse et implique peu d'étapes à partir des produits commerciaux.