Correction: Conformationally restricted benzothienoazepine respiratory syncytial virus inhibitors: their synthesis, structural analysis and biological activities

Euan A F Fordyce, S Fraser Hunt, Damien Crepin, Stuart T Onions, Guillaume F Parra, Chris J Sleigh, John King-Underwood, Harry Finch, John Murray

Correction for ‘Conformationally restricted benzothienoazepine respiratory syncytial virus inhibitors: their synthesis, structural analysis and biological activities’ by Euan A. F. Fordyce et al., Med. Chem. Commun., 2018, DOI: 10.1039/c8md00033f.

The authors regret that the information in note 17 in the References section of the manuscript gives an incorrect ratio of the isomers. The correct information is as follows:

17. The major impurity present in the mixture (29% isolated yield) was the corresponding propenyl thiophene 24, present as a 4 : 1 mixture of trans : cis isomers, which presumably form via elimination of triphenylphosphine oxide from the intermediate alkyloxytriphenylphosphonium species.

In addition, the wording in the Acknowledgements should be amended as follows:

The authors would like to thank Dr Kaz Ito (Pulmocide Ltd.) and Heather Allen (Pulmocide Ltd.) for the provision of the biological screening data for compounds 8a, 14 and 20.

The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.

Atropisomeric drug substances are known to have different biological properties. Compounds containing the N-benzoylbenzazepine motif have been shown to exhibit energetically restricted rotation around the Ar(CO)N axis. Herein we report, for the first time, the synthesis, physical characterisation and anti-viral profiles of a series of C-4 and C-5 methylated thieno-benzazepines. NMR analysis reveals that incorporation of a single additional substituent at either of these loci influences the conformational dynamics of the azepine ring system. In the case of the C-5 alkyl analogues, the influence of the new stereocentre is so pronounced that its absolute configuration determines which unique atropisomer is obtained following the generation of the benzazepine nucleus. Screening of the alkylated derivatives for their anti-respiratory syncytial virus (RSV) activity indicates that the desired viral pathogenicity is strongly associated with the conformation adopted by the modified tricyclic scaffolds. This is particularly evident in the case of the C-5 homologues in which one atropisomer was found to be potently active and the other essentially inert. These results provide compelling evidence that we have determined the bioactive conformation shared by RSV inhibitors that employ the thienobenazapine nucleus as their core molecular architecture. Furthermore, the understanding obtained from these studies may make it possible to design improved agents against RSV infection in the future.

Ref: MedChemComm 2018