6-chloro-8-(2,5-dichlorophenylthio)-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridine

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 6-chloro-8-(2,5-dichlorophenylthio)-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridine
• 英文别名: 2-(Benzenesulfonylmethyl)-6-chloro-8-(2,5-dichlorophenyl)sulfanyl-3-nitroimidazo[1,2-a]pyridine；2-(benzenesulfonylmethyl)-6-chloro-8-(2,5-dichlorophenyl)sulfanyl-3-nitroimidazo[1,2-a]pyridine
• 化学式: C₂₀H₁₂Cl₃N₃O₄S₂
• 分子量: 528.824
• InChiKey: SBUVGVRFLSNCAS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  131
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,5-二氯苯硫酚 、 8-bromo-6-chloro-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridine 在 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 反应 0.5h， 以31%的产率得到6-chloro-8-(2,5-dichlorophenylthio)-3-nitro-2-(phenylsulfonylmethyl)imidazo[1,2-a]pyridine
  参考文献：
  名称：

  Nongenotoxic 3-Nitroimidazo[1,2-a]pyridines Are NTR1 Substrates That Display Potent in Vitro Antileishmanial Activity

  摘要：

  Twenty nine original 3-nitroimidazo[1,2-a]pyridine derivatives, bearing a phenylthio (or benzylthio) moiety at position 8 of the scaffold, were synthesized. In vitro evaluation highlighted compound 5 as an antiparasitic hit molecule displaying low cytotoxicity for the human HepG2 cell line (CC50 > 100 mu M) alongside good antileishmanial activities (IC50 = 1-2.1 mu M) against L. donovani, L. infantum, and L. major; and good antitrypanosomal activities (IC50 = 1.3-2.2 mu M) against T. brucei brucei and T. cruzi, in comparison to several reference drugs such as miltefosine, fexinidazole, eflornithine, and benznidazole (IC50 = 0.6 to 13.3 mu M). Molecule 5, presenting a low reduction potential (E degrees = -0.63 V), was shown to be selectively bioactivated by the L. donovani type 1 nitroreductase (NTR1). Importantly, molecule 5 was neither mutagenic (negative Ames test), nor genotoxic (negative comet assay), in contrast to many other nitroaromatics. Molecule 5 showed poor microsomal stability; however, its main metabolite (sulfoxide) remained both active and nonmutagenic, making 5 a good candidate for further in vivo studies.

  DOI：

  10.1021/acsmedchemlett.8b00347

文献信息

• Nongenotoxic 3-Nitroimidazo[1,2-<i>a</i>]pyridines Are NTR1 Substrates That Display Potent <i>in Vitro</i> Antileishmanial Activity
  作者：Cyril Fersing、Louise Basmaciyan、Clotilde Boudot、Julien Pedron、Sébastien Hutter、Anita Cohen、Caroline Castera-Ducros、Nicolas Primas、Michèle Laget、Magali Casanova、Sandra Bourgeade-Delmas、Mélanie Piednoel、Alix Sournia-Saquet、Valère Belle Mbou、Bertrand Courtioux、Élisa Boutet-Robinet、Marc Since、Rachel Milne、Susan Wyllie、Alan H. Fairlamb、Alexis Valentin、Pascal Rathelot、Pierre Verhaeghe、Patrice Vanelle、Nadine Azas

  DOI：10.1021/acsmedchemlett.8b00347

  日期：2019.1.10

  Twenty nine original 3-nitroimidazo[1,2-a]pyridine derivatives, bearing a phenylthio (or benzylthio) moiety at position 8 of the scaffold, were synthesized. In vitro evaluation highlighted compound 5 as an antiparasitic hit molecule displaying low cytotoxicity for the human HepG2 cell line (CC50 > 100 mu M) alongside good antileishmanial activities (IC50 = 1-2.1 mu M) against L. donovani, L. infantum, and L. major; and good antitrypanosomal activities (IC50 = 1.3-2.2 mu M) against T. brucei brucei and T. cruzi, in comparison to several reference drugs such as miltefosine, fexinidazole, eflornithine, and benznidazole (IC50 = 0.6 to 13.3 mu M). Molecule 5, presenting a low reduction potential (E degrees = -0.63 V), was shown to be selectively bioactivated by the L. donovani type 1 nitroreductase (NTR1). Importantly, molecule 5 was neither mutagenic (negative Ames test), nor genotoxic (negative comet assay), in contrast to many other nitroaromatics. Molecule 5 showed poor microsomal stability; however, its main metabolite (sulfoxide) remained both active and nonmutagenic, making 5 a good candidate for further in vivo studies.