title: Synthesis and biological profile of new 1,2,3,4-tetrahydroisoquinolines as selective carbonic anhydrase inhibitors.
abstract: In a previous paper we identified several 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-2-sulfonamides that displayed inhibitory effects toward selected carbonic anhydrase isozymes at micromolar concentration. In order to deepen the structure-activity relationships (SARs) and identify novel compounds with improved activity, we synthesized a series of monomethoxy analogues of the previously investigated dimethoxy derivatives. The evaluation of biological profile has been focused on in vitro effects against several CA isoforms. The new monomethoxy derivatives showed higher hCA inhibitory effects against several isoforms compared to the dimethoxy analogues. Particularly, some of these compounds (e.g., 1b and 1h) showed low nanomolar K(I) values and excellent selectivity for hCA IX and hCA XIV versus hCA I and II inhibition.
authors: Dipartimento Farmaco-Chimico, Università di Messina, Viale Annunziata, I-98168 Messina, Italy.
authors: Rosaria
authors: R
authors: Gitto
authors: Francesca Maria
authors: FM
authors: Damiano
authors: Laura
authors: L
authors: De Luca
authors: Stefania
authors: S
authors: Ferro
authors: Daniela
authors: D
authors: Vullo
authors: Claudiu T
authors: CT
authors: Supuran
authors: Alba
authors: A
authors: Chimirri
mesh_terms: D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D044005:Tetrahydroisoquinolines