6268-18-4Relevant articles and documents
The discovery of 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 1
Bond, Silas,Draffan, Alistair G.,Fenner, Jennifer E.,Lambert, John,Lim, Chin Yu,Lin, Bo,Luttick, Angela,Mitchell, Jeffrey P.,Morton, Craig J.,Nearn, Roland H.,Sanford, Vanessa,Stanislawski, Pauline C.,Tucker, Simon P.
, p. 969 - 975 (2015/02/19)
Respiratory syncytial virus (RSV) is a major cause of respiratory tract infections in infants, young children and adults. Compound 1a (9b-(4-chlorophenyl)-1-(4-fluorobenzoyl)-1,2,3,9b-tetrahydro-5H-imidazo[2,1-a]isoindol-5-one) was identified as an inhibitor of A and B strains of RSV targeting the fusion glycoprotein. SAR was developed by systematic exploration of the phenyl (R1) and benzoyl (R2) groups. Furthermore, introduction of a nitrogen at the 8-position of the tricyclic core resulted in active analogues with improved properties (aqueous solubility, protein binding and log D) and excellent rat pharmacokinetics (e.g., rat oral bioavailability of 89% for compound 17).