Author/Authors :
Lars J.S. Knutsen، نويسنده , , Christopher J. Hobbs، نويسنده , , Christopher G. Earnshaw، نويسنده , , Andrea Fiumana، نويسنده , , Jenny Gilbert، نويسنده , , Sarah L. Mellor، نويسنده , , Fleur Radford، نويسنده , , Nichola J. Smith، نويسنده , , Philip J. Birch، نويسنده , , J. Russell Burley، نويسنده , , Stuart D.C. Ward، نويسنده , , Iain F. James، نويسنده ,
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. The new compounds described have potential in treatment of neuropathic pain.
