Tandem synthesis and in vitro antiplasmodial evaluation of new naphtho[2,1-d] thiazole derivatives

Anita D Cohen (1) , Pierre Verhaeghe (2) , Maxime D. Crozet (3) , Sébastien Hutter (1) , Pascal Rathelot (4) , Patrice Vanelle (4) , Nadine D Azas (1)

1 IP-TPT - Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques
2 LCC - Laboratoire de chimie de coordination
3 CBRL - Chimie, biologie et radicaux libres - UMR 6517
4 ICR - Institut de Chimie Radicalaire

A series of naphtho[2,1-d]thiazoles was prepared in good yields under microwave irradiation with an original protocol combining tandem direct arylation and intramolecular Knoevenagel reaction on 1,3-thiazole derivatives. Antiplasmodial evaluation of this series highlighted two hit compounds (compounds 11 and 13) displaying promising in vitro activity on the multiresistant K1 Plasmodium falciparum strain. Structure-toxicity and structure activity relationships are also discussed and reveal the importance of the R-1 and R-4 substituents of the naphthyl moiety for the biological profile of the series. (C) 2012 Elsevier Masson SAS. All rights reserved.

Domains: Chemical Sciences

Anita D Cohen, Pierre Verhaeghe, Maxime D. Crozet, Sébastien Hutter, Pascal Rathelot, et al.. Tandem synthesis and in vitro antiplasmodial evaluation of new naphtho[2,1-d] thiazole derivatives. European Journal of Medicinal Chemistry, 2012, 55, pp.315--324. ⟨10.1016/j.ejmech.2012.07.034⟩. ⟨hal-01460344⟩