Diamino benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 3. Enhancing activity by imposing conformational restriction in the C-4" side chain.

The preparation and biological evaluation of a series of benzo[b]thiophene diamine thrombin inhibitors possessing conformationally restricted C-4" linkers are reported. Compared to the parent compounds 1a/b, the unsaturated derivatives 3a/b exhibited a modest twofold increase in thrombin inhibitory activity, while the more lipophilic carbocyclic ring containing analogs 4a/b affected an eightfold enhancement in potency.