title: 1,2,3,9b-Tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones as a new class of respiratory syncytial virus (RSV) fusion inhibitors. Part 2: identification of BTA9881 as a preclinical candidate.
abstract: Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, young children and adults. 1,2,3,9b-Tetrahydro-5H-imidazo[2,1-a]isoindol-5-ones with general structure 1 were previously identified as promising inhibitors of RSV targeting the fusion glycoprotein. In particular, the introduction of a nitrogen at the 8-position of the tricyclic core yielded lead compounds 2 and 3. Extensive exploration of the R(2) group established that certain heterocyclic amides conferred potent RSV A&B activity and a good balance of physicochemical and pharmacokinetic properties. The antiviral activity was found to reside in a single enantiomer and compound 33a, (9bS)-9b-(4-chlorophenyl)-1-(pyridin-3-ylcarbonyl)-1,2,3,9b-tetrahydro-5H-imidazo[1',2':1,2]pyrrolo[3,4-c]pyridin-5-one (known as BTA9881), was identified as a candidate for preclinical development.
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Silas
authors.initials: S
authors.lastname: Bond
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia. Electronic address: a.draffan@biota.com.au.
authors.forename: Alistair G
authors.initials: AG
authors.lastname: Draffan
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Fenner
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Lambert
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Chin Yu
authors.initials: CY
authors.lastname: Lim
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Bo
authors.initials: B
authors.lastname: Lin
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Luttick
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Mitchell
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Morton
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Roland H
authors.initials: RH
authors.lastname: Nearn
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Sanford
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Kelly H
authors.initials: KH
authors.lastname: Anderson
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Mayes
authors.affiliation: Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
authors.forename: Simon P
authors.initials: SP
authors.lastname: Tucker
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D008561:Membrane Fusion / Q000187:drug effects*; D012136:Respiratory Syncytial Viruses / Q000187:drug effects* / Q000502:physiology
chemical_list: D000998:Antiviral Agents; C000602034:BTA9881; D007093:Imidazoles
keywords: Antiviral; Respiratory syncytial virus; Synthesis