N-Cyclopropyl-5,6-dihydro-6-[4-[[[2-(2-oxa-7-azaspiro[3.5]non-7-yl)-3-pyridinyl]carbonyl]amino]benzoyl]-4H-thieno[3,2-d][1]benzazepine-2-carboxamide is a possible respiratory syncytial virus (RSV) RNA polymerase inhibitor.
This RSV inhibitor (FW = 633.77 g/mol) targets Respiratory Syncytial Virus, inhibiting both mRNA transcription and genome replication in cell based mini-genome assays, suggesting it targets a step common to both of these RNA synthesis processes. Analysis in an in vitro transcription run-on assay, containing RSV nucleocapsids, showed that AZ-27 inhibits (IC50 ≈ 15 nM) the synthesis of transcripts from the 3′-end of the genome to a greater extent than those from the 5′-end, indicating that it inhibits transcription initiation. In experiments assaying polymerase activity on the promoter, AZ-27 inhibits transcription and replication initiation. The RSV polymerase also utilizes the promoter sequence to perform a back-priming reaction. Addition of AZ-27 has no effect on the addition of up to three nucleotides by back-priming, but inhibits further extension of the back primed RNA. These findings suggest that the RSV polymerase is likely to adopt different conformations to execute its separate functions at the promoter.
