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).

呼吸道合胞病毒（RSV）是婴儿，幼儿和成人呼吸道感染的主要原因。化合物1A（9 b - （4-氯苯基）-1-（4-氟苯甲酰基）-1,2,3,9- b -四氢-5- ħ -咪唑并[2,1-一个]异吲哚-5-酮）被确定作为针对融合糖蛋白的RSV A和B株的抑制剂。SAR是通过对苯基（R ¹）和苯甲酰基（R ²）基团进行系统性探索而开发的。此外，在三环核的8位上引入氮导致活性类似物具有改善的性能（水溶性，蛋白质结合和log  D）和出色的大鼠药代动力学（例如，化合物17的大鼠口服生物利用度为89％）。