6-Chloro-3-nitro-2-[(phenylsulfonyl)methyl]imidazo[1,2-<i>b</i>]pyridazine

oleh: Romain Paoli-Lombardo, Nicolas Primas, Sébastien Hutter, Sandra Bourgeade-Delmas, Clotilde Boudot, Caroline Castera-Ducros, Inès Jacquet, Bertrand Courtioux, Nadine Azas, Pascal Rathelot, Patrice Vanelle

Format: Article
Diterbitkan: MDPI AG 2023-02-01

Deskripsi

As part of our ongoing scaffold-hopping work on an antikinetoplastid 3-nitroimidazo[1,2-<i>a</i>]pyridine scaffold, we explored 3-nitroimidazo[1,2-<i>b</i>]pyridazine as a potential new antikinetoplastid series. Using conditions previously described by our lab, we obtained 6-chloro-3-nitro-2-[(phenylsulfonyl)methyl]imidazo[1,2-<i>b</i>]pyridazine with 54% yield. In vitro activity of this compound was evaluated against both the promastigote form of <i>Leishmania donovani</i>, the axenic amastigote form of <i>Leishmania infantum</i> and the trypomastigote blood stream form of <i>Trypanosomabrucei brucei</i>, and its influence on cell viability was assessed on the HepG2 cell line. However, despite good activity against the trypomastigote blood stream form of <i>T. b. brucei</i> (EC<sub>50</sub> = 0.38 µM), it showed poor solubility in both HepG2 (CC<sub>50</sub> > 7.8 µM) and <i>L. infantum</i> axenic amastigotes (EC<sub>50</sub> > 1.6 µM) culture media, associated with a loss of activity against the promastigote form of <i>L. infantum</i> (EC<sub>50</sub> > 15.6 µM).