Novel N-thiazolyl piperazine-1-carboxamide CCR2 antagonists – investigation of an unexpected reaction with glutathione

A series of CCR2 antagonists containing halothiazoles were found to undergo an unexpected reaction with glutathione. Experiments revealed the structure-reactivity relationship and calculations suggest that competition between two reactions of a tautomer of the reactant (deprotonation and nucleophilic addition) governs the rate of this reaction.