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.
MeSH terms
-
Analgesics / chemical synthesis*
-
Analgesics / pharmacology*
-
Calcium Channel Blockers / chemical synthesis*
-
Calcium Channel Blockers / pharmacology*
-
Calcium Channels, L-Type / drug effects
-
Calcium Channels, N-Type / drug effects*
-
Cell Line, Tumor
-
Chromatography, High Pressure Liquid
-
Drug Evaluation, Preclinical
-
Humans
-
Indicators and Reagents
-
Spectrophotometry, Ultraviolet
-
Structure-Activity Relationship
-
Thiazolidinediones / chemical synthesis*
-
Thiazolidinediones / pharmacology*
Substances
-
Analgesics
-
Calcium Channel Blockers
-
Calcium Channels, L-Type
-
Calcium Channels, N-Type
-
Indicators and Reagents
-
Thiazolidinediones