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

  • Bioorg Med Chem Lett. 2015 Feb 15;25(4):976-81. doi: 10.1016/j.bmcl.2014.11.024.
Silas Bond  1 ,  Alistair G Draffan  2 ,  Jennifer E Fenner  1 ,  John Lambert  1 ,  Chin Yu Lim  1 ,  Bo Lin  1 ,  Angela Luttick  1 ,  Jeffrey P Mitchell  1 ,  Craig J Morton  1 ,  Roland H Nearn  1 ,  Vanessa Sanford  1 ,  Kelly H Anderson  1 ,  Penelope A Mayes  1 ,  Simon P Tucker  1
Affiliations
  • 1. Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia.
  • 2. Biota Scientific Management Pty Ltd, 10/585 Blackburn Road, Notting Hill, Victoria 3168, Australia. Electronic address: [email protected].
PMID: 25595685 DOI: 10.1016/j.bmcl.2014.11.024
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.

Keywords
Antiviral; Respiratory syncytial virus; Synthesis.
Products