title: Synthesis and pharmacological evaluation of Tic-hydantoin derivatives as selective sigma1 ligands. Part 2.
abstract: Herein is described a new class of selective sigma1 ligands consisting of tetrahydroisoquinoline-hydantoin (Tic-hydantoin) derivatives. Compound 1a has high affinity (IC50 = 16 nM) for sigma1 receptor and is selective in a large panel of therapeutic targets. This study presents structural changes on the side chain of the Tic-hydantoin core. Analogs of higher affinity could be identified (IC50 approximately 2-3 nM).
authors.affiliation: UMR CNRS 8525, Université de Lille II, Institut de Biologie et Institut Pasteur de Lille 1 rue du Professeur Calmette, B.P. 447, 59021 Lille cedex, France.
authors.forename: Amaury
authors.initials: A
authors.lastname: Cazenave Gassiot
authors.forename: Julie
authors.initials: J
authors.lastname: Charton
authors.forename: Sophie
authors.initials: S
authors.lastname: Girault-Mizzi
authors.forename: Pauline
authors.initials: P
authors.lastname: Gilleron
authors.forename: Marie-Ange
authors.initials: MA
authors.lastname: Debreu-Fontaine
authors.forename: Christian
authors.initials: C
authors.lastname: Sergheraert
authors.forename: Patricia
authors.initials: P
authors.lastname: Melnyk
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis; D002470:Cell Survival / Q000187:drug effects; D006168:Guinea Pigs; D006827:Hydantoins / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008024:Ligands; D017480:Receptors, sigma / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000928:Antidepressive Agents; D006827:Hydantoins; D008024:Ligands; D017480:Receptors, sigma