bis(4-chlorophenyl)(4-(pyrrolidin-1-ylmethyl)phenyl)methanol | 949934-26-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: bis(4-chlorophenyl)(4-(pyrrolidin-1-ylmethyl)phenyl)methanol
• 英文别名: bis(4-chloro-phenyl)(4-(pyrrolidin-1-ylmethyl)phenyl)methanol；Bis(4-chlorophenyl)-[4-(pyrrolidin-1-ylmethyl)phenyl]methanol
• CAS: 949934-26-3
• 化学式: C₂₄H₂₃Cl₂NO
• 分子量: 412.359
• InChiKey: FBZFQMKWHFQNPS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  bis(4-chlorophenyl)(4-(pyrrolidin-1-ylmethyl)phenyl)methanol 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.33h， 生成
  参考文献：
  名称：

  Exploring clotrimazole-based pharmacophore: 3D-QSAR studies and synthesis of novel antiplasmodial agents

  摘要：

  We report herein the generation and validation of a 3D-QSAR model based on a set of antimalarials previously described by us and characterized by a clotrimazole-based pharmacophore. A novel series of derivatives was synthesized and showed activity against Plasmodium falciparum chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) strains. Gratifyingly, compounds 35a-c showed interesting activity against P. falciparum CQ-R strains with improved predicted physico-chemical properties. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.007
• 作为产物：
  描述：

  (4-氯苯基)[4-(1-吡咯烷基甲基)苯基]甲酮 、 4-溴氯苯 在 magnesium 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 以66%的产率得到bis(4-chlorophenyl)(4-(pyrrolidin-1-ylmethyl)phenyl)methanol
  参考文献：
  名称：

  Exploring clotrimazole-based pharmacophore: 3D-QSAR studies and synthesis of novel antiplasmodial agents

  摘要：

  We report herein the generation and validation of a 3D-QSAR model based on a set of antimalarials previously described by us and characterized by a clotrimazole-based pharmacophore. A novel series of derivatives was synthesized and showed activity against Plasmodium falciparum chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) strains. Gratifyingly, compounds 35a-c showed interesting activity against P. falciparum CQ-R strains with improved predicted physico-chemical properties. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.09.007

文献信息

• Optimization of 4-Aminoquinoline/Clotrimazole-Based Hybrid Antimalarials: Further Structure–Activity Relationships, in Vivo Studies, and Preliminary Toxicity Profiling
  作者：Sandra Gemma、Caterina Camodeca、Salvatore Sanna Coccone、Bhupendra P. Joshi、Matteo Bernetti、Vittoria Moretti、Simone Brogi、Maria Cruz Bonache de Marcos、Luisa Savini、Donatella Taramelli、Nicoletta Basilico、Silvia Parapini、Matthias Rottmann、Reto Brun、Stefania Lamponi、Silvio Caccia、Giovanna Guiso、Robert L. Summers、Rowena E. Martin、Simona Saponara、Beatrice Gorelli、Ettore Novellino、Giuseppe Campiani、Stefania Butini

  DOI：10.1021/jm300802s

  日期：2012.8.9

  the treatment of infections. We recently reported the development of a novel antimalarial drug that combines the 4-aminoquinoline pharmacophore of chloroquine with that of clotrimazole-based antimalarials. Here we describe the optimization of this class of hybrid drug through in-depth structure–activity relationship studies. Antiplasmodial properties and mode of action were characterized in vitro and

  尽管最近在抗击疟疾方面取得了进展，但耐药性寄生虫的出现和扩散仍然是感染治疗的严重障碍。我们最近报道了一种新型抗疟药的开发，该药结合了氯喹的4-氨基喹啉药效基团和基于克霉唑的抗疟药。在这里，我们通过深入的结构-活性关系研究来描述这类杂合药物的优化。在体外和体内表征了抗疟原虫的性质和作用方式，并在非洲爪蟾卵母细胞表达系统中研究了与寄生虫的“氯喹抗性转运蛋白”的相互作用。这些测试表明哌嗪衍生物4b和4d可能适合与氯喹共同使用，以抵抗耐氯喹的寄生虫。在计算机上测定了细胞色素P450代谢药物的潜力，并测试了先导化合物的毒性和致突变性。在小鼠中进行的初步药代动力学分析表明，化合物4b具有最佳的半衰期。
• [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.
• Exploring clotrimazole-based pharmacophore: 3D-QSAR studies and synthesis of novel antiplasmodial agents
  作者：Simone Brogi、Margherita Brindisi、Bhupendra P. Joshi、Salvatore Sanna Coccone、Silvia Parapini、Nicoletta Basilico、Ettore Novellino、Giuseppe Campiani、Sandra Gemma、Stefania Butini

  DOI：10.1016/j.bmcl.2015.09.007

  日期：2015.11

  We report herein the generation and validation of a 3D-QSAR model based on a set of antimalarials previously described by us and characterized by a clotrimazole-based pharmacophore. A novel series of derivatives was synthesized and showed activity against Plasmodium falciparum chloroquine-sensitive (CQ-S) and chloroquine-resistant (CQ-R) strains. Gratifyingly, compounds 35a-c showed interesting activity against P. falciparum CQ-R strains with improved predicted physico-chemical properties. (C) 2015 Elsevier Ltd. All rights reserved.