Synthesis and pharmacological evaluation of Tic-hydantoin derivatives as selective sigma1 ligands. Part 1.
Herein is described a new class of selective sigma1 ligands consisting of tetrahydroisoquinoline-hydantoin (Tic-hydantoin) derivatives. Compound 3a has high affinity (IC50 = 16 nM) for the sigma1 receptor and is selective in a large panel of therapeutic targets. This first study presents structural changes around the Tic-hydantoin core, leading to a Tic-hydantoin analogue with a higher sigma1 affinity (IC50 approximately 1 nM).
Charton
Julie
J
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.
Cazenave Gassiot
Amaury
A
Girault-Mizzi
Sophie
S
Debreu-Fontaine
Marie-Ange
MA
Melnyk
Patricia
P
Sergheraert
Christian
C
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
D000928:Antidepressive Agents; D006827:Hydantoins; D008024:Ligands; D017480:Receptors, sigma