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

…, CJ Hobbs, CG Earnshaw, A Fiumana, J Gilbert…

Index: Knutsen, Lars J.S.; Hobbs, Christopher J.; Earnshaw, Christopher G.; Fiumana, Andrea; Gilbert, Jenny; Mellor, Sarah L.; Radford, Fleur; Smith, Nichola J.; Birch, Philip J.; Russell Burley; Ward, Stuart D.C.; James, Iain F. Bioorganic and Medicinal Chemistry Letters, 2007 , vol. 17, # 3 p. 662 - 667

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Citation Number: 59

Abstract

A series of new N-type (Cav2. 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 μM in an in vitro IMR32 assay, and selectivities for N/L of up to 30-fold. ...