(+/-)-(4-chlorophenyl)[4-(pyrrolidin-1-ylmethyl)phenyl]methanol | 927690-08-2

• 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-chlorophenyl)[4-(pyrrolidin-1-ylmethyl)phenyl]methanol
• 英文别名: (4-Chlorophenyl)-[4-(pyrrolidin-1-ylmethyl)phenyl]methanol
• CAS: 927690-08-2
• 化学式: C₁₈H₂₀ClNO
• 分子量: 301.816
• InChiKey: TZBKUDJDOPNEQC-UHFFFAOYSA-N

物化性质

• 沸点：
  441.4±40.0 °C(Predicted)
• 密度：
  1.218±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 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：

  (+/-)-(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 3.83h， 生成
  参考文献：
  名称：

  Design and Synthesis of Potent Antimalarial Agents Based on Clotrimazole Scaffold:  Exploring an Innovative Pharmacophore

  摘要：

  Identification of new molecular scaffolds structurally unrelated to known antimalarials may represent a valid strategy to overcome resistance of P. falciparum (Pf) to currently available drugs. We describe herein the investigation of a new polycyclic pharmacophore, related to clotrimazole, to develop innovative antimalarial agents. This study allowed us to discover compounds characterized by a high in vitro potency, particularly against Pf CQ-resistant strains selectively targeting free heme, which are easy to synthesize by low-cost synthetic strategies.

  DOI：

  10.1021/jm061429p
• 作为产物：
  描述：

  1-(4-溴苯甲基)吡咯烷 、 4-氯苯甲醛 在 magnesium 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以74%的产率得到(+/-)-(4-chlorophenyl)[4-(pyrrolidin-1-ylmethyl)phenyl]methanol
  参考文献：
  名称：

  WO2007/104696

  摘要：

  公开号：

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。
• WO2007/104696
  申请人：——

  公开号：——

  公开（公告）日：——
• [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.
• Design and Synthesis of Potent Antimalarial Agents Based on Clotrimazole Scaffold:  Exploring an Innovative Pharmacophore
  作者：Sandra Gemma、Giuseppe Campiani、Stefania Butini、Gagan Kukreja、Bhupendra P. Joshi、Marco Persico、Bruno Catalanotti、Ettore Novellino、Ernesto Fattorusso、Vito Nacci、Luisa Savini、Donatella Taramelli、Nicoletta Basilico、Giulia Morace、Vanessa Yardley、Caterina Fattorusso

  DOI：10.1021/jm061429p

  日期：2007.2.1

  Identification of new molecular scaffolds structurally unrelated to known antimalarials may represent a valid strategy to overcome resistance of P. falciparum (Pf) to currently available drugs. We describe herein the investigation of a new polycyclic pharmacophore, related to clotrimazole, to develop innovative antimalarial agents. This study allowed us to discover compounds characterized by a high in vitro potency, particularly against Pf CQ-resistant strains selectively targeting free heme, which are easy to synthesize by low-cost synthetic strategies.