(Hetero)aryl substituted thiazol-2,4-yl scaffold as human carbonic anhydrase I, II, VII and XIV activators

Marouan Rami (1) , Jean-Yves Winum (2) , Claudiu T Supuran (3) , Patricia Melnyk (1) , Saïd Yous (1)

1 JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer - U837
2 IBMM - Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
3 UniFI - Università degli Studi di Firenze = University of Florence = Université de Florence

Using histamine as lead molecule, a library of (hetero)aryl substituted thiazol-2,4-yl derivatives incorporating pyridine as proton shuttling moiety were obtained and investigated as activators of human carbonic anhydrase (CA, EC 4.2.1.1) isoforms I, II, VII and XIV. Some derivatives displayed good activating and select-ivity profiles. This study provides an interesting opportunity to study the thiazole scaffold for the design of CA activators (CAAs), possibly acting on the central nervous system and targeting pathologies involving memory and learning impairments.

Mots clés: Thiazole scaffold; carbonic anhydrase activators; isozymes; drug design; synthesis

Domaines: Chimie thérapeutique; Chimie organique

Marouan Rami, Jean-Yves Winum, Claudiu T Supuran, Patricia Melnyk, Saïd Yous. (Hetero)aryl substituted thiazol-2,4-yl scaffold as human carbonic anhydrase I, II, VII and XIV activators. Journal of Enzyme Inhibition and Medicinal Chemistry, 2019, 34 (1), pp.224-229. ⟨10.1080/14756366.2018.1543292⟩. ⟨hal-02060639⟩