1-(9H-fluoren-9-yl)-4-(phenylsulfonyl)piperazine

• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 英文名称: 1-(9H-fluoren-9-yl)-4-(phenylsulfonyl)piperazine
• 英文别名: 1-(benzenesulfonyl)-4-(9H-fluoren-9-yl)piperazine
• 化学式: C₂₃H₂₂N₂O₂S
• 分子量: 390.506
• InChiKey: BPRDZUCBLIONCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  49
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  9-溴芴 在 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 1-(9H-fluoren-9-yl)-4-(phenylsulfonyl)piperazine
  参考文献：
  名称：

  Design, synthesis and evaluation of new GEQ derivatives as inhibitors of InhA enzyme and Mycobacterium tuberculosis growth

  摘要：

  A series of fluorene-based derivatives was synthesized and evaluated for inhibiting both InhA and Mycobacterium tuberculosis growth. These compounds were inspired by the previously reported Genz-10850 molecule, a good InhA inhibitor, but with a poor activity against M. tuberculosis growth. Structure activity relationships were performed by introducing the following chemical modifications: 1) the piperazine ring; 2) the amide group; 3) the aryl moiety; and 4) the fluorene moiety. Among these new derivatives, one of them was more effective against both the InhA activity and mycobacterial growth, compared to the hit compound. Docking studies were also performed to rationalize activities of these derivatives. Furthermore, we showed for the first time that efflux pump inhibitors potentiated the efficacy of Genz-10850 (GEQ) derivatives against M. tuberculosis growth, demonstrating that these compounds could be substrates of some efflux pumps. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.06.035

文献信息

• Piperazine derivatives: Synthesis, inhibition of the Mycobacterium tuberculosis enoyl-acyl carrier protein reductase and SAR studies
  作者：Mariane Rotta、Kenia Pissinate、Anne Drumond Villela、Davi Fernando Back、Luis Fernando Saraiva Macedo Timmers、José Fernando Ruggiero Bachega、Osmar Norberto de Souza、Diógenes Santiago Santos、Luiz Augusto Basso、Pablo Machado

  DOI：10.1016/j.ejmech.2014.11.034

  日期：2015.1

  in the submicromolar range. A structure–activity relationship (SAR) evaluation indicated the importance of the chemical environment surrounding the carbonyl group for inhibition. In addition, the structure of one selected compound was supported by crystallographic studies, and experimental geometrical values were compared with semi-empirical quantum chemical calculations. Furthermore, the mode of inhibition

  在结核分枝杆菌NADH依赖性烯酰基-酰基载体蛋白还原酶（玛INHA）催化氢化物转移到长链烯酰基硫酯的底物。Mt InhA是II型分枝杆菌解离的脂肪酸生物合成系统的成员，并且是异烟肼的真正靶点，异烟肼是治疗肺结核的最处方药。在这里，合成了一系列哌嗪衍生物，并筛选了它们作为Mt InhA抑制剂，从而用IC 50鉴定了化合物值在亚微摩尔范围内。结构-活性关系（SAR）评估表明，羰基周围的化学环境对于抑制作用非常重要。此外，一种选择的化合物的结构得到晶体学研究的支持，并将实验几何值与半经验量子化学计算进行了比较。此外，确定了九种活性最高的化合物的抑制方式和抑制解离常数。这些发现表明，这9个含H-氟-9-基-哌嗪的化合物在烯酰基硫酯（2-反式-十二烯酰基-CoA）底物结合位点与Mt InhA相互作用。