2. Academic Validation
  3. Synthesis and SAR of novel 2-arylthiazolidinones as selective analgesic N-type calcium channel blockers

Synthesis and SAR of novel 2-arylthiazolidinones as selective analgesic N-type calcium channel blockers

  • Bioorg Med Chem Lett. 2007 Feb 1;17(3):662-7. doi: 10.1016/j.bmcl.2006.10.098.
Lars J S Knutsen 1,  Christopher J Hobbs,  Christopher G Earnshaw,  Andrea Fiumana,  Jenny Gilbert,  Sarah L Mellor,  Fleur Radford,  Nichola J Smith,  Philip J Birch,  J Russell Burley,  Stuart D C Ward,  Iain F James
Affiliations

Affiliation

  • 1 Ionix Pharmaceuticals Ltd, 418 Cambridge Science Park, Milton Road, Cambridge CB4 0PA, UK. LKnutsen@cephalon.com
PMID: 17134896 DOI: 10.1016/j.bmcl.2006.10.098
Abstract

A series of new N-type (CA(v)2.2) Calcium Channel blockers derived from the 'hit' structures 2-(3-bromo-4-fluorophenyl)-3-(2-pyridin-2-ylethyl)thiazolidin-4-one 9 and its 2-[4-(4-bromophenyl)pyridin-3-yl]-3-isobutyl analogue 10 is described. Extensive SAR studies using a range of synthetic approaches resulted in novel, patented compounds with IC50 values of up to 0.2 microM in an in vitro IMR32 assay, and selectivities for N/L of up to 30-fold. The new compounds described have potential in treatment of neuropathic pain.

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