Parallel synthesis of a biased library of thiazolidinones as novel sodium channel antagonists.
A biased chemical library containing 91 differentially substituted thiazolidinones was prepared in an effort to improve the pharmacology of a known anticonvulsant agent V102862. The collection was prepared in a single step multi-component condensation reaction that produced good yields and very high crude purity (75%-85%). Seven compounds, identified within the library were shown to be more potent than V102862, our parent reference compound, in an electrophysiological assay measuring sodium channel antagonism. The most potent compound, 3-(2-piperidinylethyl)-2-(3-(3-trifluoromethylphenoxy)phenyl)thiazolidinone, has a Ki of 90 nM.
Sun
Qun
Q
Purdue Pharma LP, Cranbury, NJ 08512, USA.
Tafesse
Laykea
L
Limberis
James T
JT
Islam
Khondekar
K
Kyle
Donald J
DJ
D000818:Animals; D020650:Combinatorial Chemistry Techniques; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects; D026941:Sodium Channel Blockers / Q000138:chemical synthesis* / Q000494:pharmacology*; D014982:Xenopus laevis
D026941:Sodium Channel Blockers