4-(7-chloroquinolin-4-yl)-N-(4-chlorophenyl)piperazine-1-carboxamide | 1334723-37-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-(7-chloroquinolin-4-yl)-N-(4-chlorophenyl)piperazine-1-carboxamide
• 英文别名: N-(4-chlorophenyl)-4-(7-chloroquinolin-4-yl)piperazine-1-carboxamide
• CAS: 1334723-37-3
• 化学式: C₂₀H₁₈Cl₂N₄O
• 分子量: 401.295
• InChiKey: NTIJMSJJOHXHHM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  48.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  4,7-二氯喹啉 在 potassium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 4-(7-chloroquinolin-4-yl)-N-(4-chlorophenyl)piperazine-1-carboxamide
  参考文献：
  名称：

  Engineering another class of anti-tubercular lead: Hit to lead optimization of an intriguing class of gyrase ATPase inhibitors

  摘要：

  A structure based medium throughput virtual screening campaign of BITS-Pilani in house chemical library to identify novel binders of Mycobacterium tuberculosis gyrase ATPase domain led to the discovery of a quinoline scaffold. Further medicinal chemistry explorations on the right hand core of the early hit, engendered a potent lead demonstrating superior efficacy both in the enzyme and whole cell screening assay. The binding affinity shown at the enzyme level was further corroborated by biophysical characterization techniques. Early pharmacokinetic evaluation of the optimized analogue was encouraging and provides interesting potential for further optimization. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.06.042

文献信息

• Piperazinyl quinolines as chemosensitizers to increase fluconazole susceptibility of Candida albicans clinical isolates
  作者：Willmen Youngsaye、Benjamin Vincent、Cathy L. Hartland、Barbara J. Morgan、Sara J. Buhrlage、Stephen Johnston、Joshua A. Bittker、Lawrence MacPherson、Sivaraman Dandapani、Michelle Palmer、Luke Whitesell、Susan Lindquist、Stuart L. Schreiber、Benito Munoz

  DOI：10.1016/j.bmcl.2011.06.105

  日期：2011.9

  The effectiveness of the potent antifungal drug fluconazole is being compromised by the rise of drug-resistant fungal pathogens. While inhibition of Hsp90 or calcineurin can reverse drug resistance in Candida, such inhibitors also impair the homologous human host protein and fungal-selective chemosensitizers remain rare. The MLPCN library was screened to identify compounds that selectively reverse fluconazole resistance in a Candida albicans clinical isolate, while having no antifungal activity when administered as a single agent. A piperazinyl quinoline was identified as a new small-molecule probe (ML189) satisfying these criteria. (C) 2011 Elsevier Ltd. All rights reserved.
• Engineering another class of anti-tubercular lead: Hit to lead optimization of an intriguing class of gyrase ATPase inhibitors
  作者：Variam Ullas Jeankumar、Rudraraju Srilakshmi Reshma、Rahul Vats、Renuka Janupally、Shalini Saxena、Perumal Yogeeswari、Dharmarajan Sriram

  DOI：10.1016/j.ejmech.2016.06.042

  日期：2016.10

  A structure based medium throughput virtual screening campaign of BITS-Pilani in house chemical library to identify novel binders of Mycobacterium tuberculosis gyrase ATPase domain led to the discovery of a quinoline scaffold. Further medicinal chemistry explorations on the right hand core of the early hit, engendered a potent lead demonstrating superior efficacy both in the enzyme and whole cell screening assay. The binding affinity shown at the enzyme level was further corroborated by biophysical characterization techniques. Early pharmacokinetic evaluation of the optimized analogue was encouraging and provides interesting potential for further optimization. (C) 2016 Elsevier Masson SAS. All rights reserved.