New pyrrolobenzothiazepine derivatives as molecular probes of the 'peripheral-type' benzodiazepine receptor (PBR) binding site

Article abstract of DOI:10.1016/S0223-5234(97)83975-X

A number of new pyrrolobenzothiazepine derivatives and a pyrrolobenzothiazocine derivative have been synthesized and evaluated for their affinity towards the 'peripheral-type' benzodiazepine receptor (PBR). The new compounds were tested in rat cortex, a tissue expressing a high density of mitochondrial PBR. Some of the pyrrolobenzothiazepines exhibited IC₅₀ values in the low nanomolar range as measured by the displacement of [³H]PK 11195 binding. Compound 4i was found to be the most potent ligand for this receptor in the pyrrolobenzothiazepine subgroup with an IC₅₀ practically identical to that determined for PK 11195. Structure-affinity relationships (SARs) have been developed to elucidate the topology of the PBR binding site.