Novel medium-sized di(het)areno-fused 1,4,7-(oxa)thiadiazecines as probes for aminergic receptors

Di(het)areno-fused 1,4,7-(oxa)thiadiazecanes were synthesized by the reduction of the corresponding tenmembered lactams obtained, in turn, via the 'hydrated imidazoline ring expansion' (HIRE) methodology. Two of them displayed micromolar agonistic activity towards trace amine-associated receptor 1 (TAAR1) and no affinity towards a panel of dopamine (D2) and serotonin (5-HT1A, 5-HT2A and 5-HT7) receptors. These findings validate compounds of this chemotype as scaffolds for the design of selective aminergic receptor modulators.

Automated summary

Di(het)areno-fused 1,4,7-(oxa)thiadiazecanes were synthesized via the 'hydrated imidazoline ring expansion' (HIRE) method, with two compounds displaying micromolar agonistic activity towards TAAR1. These compounds are suitable as scaffolds for the design of selective aminergic receptor modulators.