A New Synthetic Route to Original Sulfonamide Derivatives in 2-Trichloromethylquinazoline Series: A Structure-Activity Relationship Study of Antiplasmodial Activity

Nicolas Primas (1) , Pierre Verhaeghe (1) , Anita Cohen (1, 2) , Charline Kieffer (1) , Aurélien Dumètre (2) , Sébastien Hutter (2) , Sylvain Rault (3) , Pascal Rathelot (1) , Nadine Azas (2) , Patrice Vanelle (1)

1 ICR - Institut de Chimie Radicalaire
2 IP-TPT - Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques
3 CERMN - Centre d'Etudes et de Recherche sur le Médicament de Normandie

We report herein a simple and efficient two-step synthetic approach to new 2-trichloromethylquinazolines possessing a variously substituted sulfonamide group at position 4 used to prepare new quinazolines with antiparasitic properties. Thus, an original series of 20 derivatives was synthesized, which proved to be less-toxic than previously synthesized hits on the human HepG2 cell line, but did not display significant antiplasmodial activity. A brief Structure-Activity Relationship (SAR) evaluation shows that a more restricted conformational freedom is probably necessary for providing antiplasmodial activity.

Mots clés: quinazoline; trichloromethyl group; sulfonamide; microwaves; antiplasmodial activity

Domaines: Chimie thérapeutique; Médicaments

Nicolas Primas, Pierre Verhaeghe, Anita Cohen, Charline Kieffer, Aurélien Dumètre, et al.. A New Synthetic Route to Original Sulfonamide Derivatives in 2-Trichloromethylquinazoline Series: A Structure-Activity Relationship Study of Antiplasmodial Activity. Molecules, 2012, 17 (7), pp.8105-8117. ⟨10.3390/molecules17078105⟩. ⟨hal-01772858⟩