Discovery of sisunatovir (RV521), an inhibitor of respiratory syncytial virus fusion

RV521 is an orally bioavailable inhibitor of respiratory syncytial virus (RSV) fusion that was identified after a lead optimization process based upon hits that originated from a physical property directed hit profiling exercise at Reviral. This exercise encompassed collaborations with a number of contract organizations with collaborative medicinal chemistry and virology during the optimization phase in addition to those utilized as the compound proceeded through preclinical and clinical evaluation. RV521 exhibited a mean IC50 of 1.2 nM against a panel of RSV A and B laboratory strains and clinical isolates with antiviral efficacy in the Balb/C mouse model of RSV infection. Oral bioavailability in preclinical species ranged from 42 to >100% with evidence of highly efficient penetration into lung tissue. In healthy adult human volunteers experimentally infected with RSV, a potent antiviral effect was observed with a significant reduction in viral load and symptoms compared to placebo

Spiro-indolines for the treatment and prophylaxis of respiratory syncytial virus infection (RSV)

Benzimidazoles of formula (I): wherein: one of X and Y is an N atom or a substituted C atom, and the other is CH; L o is a single bond, C 1 alkylene, C2 alkenylene or C2 alkynylene; R1 is Ci alkyl, C2 alkenyl, C2 alkynyl, 3- to 10-membered cycloalkyl, 5- to 10-membered heterocyclyl or 5- to 12- membered heteroaryl, each of which is unsubstituted or substituted; Z is halo, C i haloalkyl, nitro, -CN, -N(R )2, -OR2, -SR2, -S(=0)R 2, or -S(=0) 2R2; each R2 is independently hydrogen, Ci_ alkyl, C2. alkenyl or o C2-6 alkynyl, wherein said alkyl, alkenyl and alkynyl groups are unsubstituted or substituted; and m is 0 or 1; and the pharmaceutic ally acceptable salt thereof are inhibitors of RSV and can therefore be used to treat or prevent an RSV infection