(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

Jean-Yves Winum¹  Claudiu T. Supuran²  Patricia Melnyk³  Saïd Yous³  Marouan Rami³ 

[1] Institut des Biomolécules Max Mousseron (IBMM) UMR 5247 CNRS, ENSCM, Université de Montpellier, Bâtiment de Recherche Max Mousseron, Ecole Nationale Supérieure de Chimie de Montpellier, 240 avenue du Professeur Emile Jeanbrau, Montpellier Cedex 34296, France;Neurofarba Department, Section of Pharmaceutical and Nutriceutical Sciences, Università degli Studi di Firenze, Via Ugo Schiff 6, Sesto Fiorentino, Florence 50019, Ital;Université de Lille, Inserm, CHU Lille, UMR-S 1172-JPArc-Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, Lille 59000, France;

关键词: Thiazole scaffold;    carbonic anhydrase activators;    isozymes;    drug design;    synthesis;   

DOI  :  10.1080/14756366.2018.1543292

来源: publisher

【 摘 要 】

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 selectivity 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.

【 授权许可】

CC BY