2-[[6-[[[2-(3-Hydroxypropyl)-5-methylphenyl]amino]methyl]-2-[[3-(morpholin-4-yl)propyl]amino]benzimidazol-1-yl]methyl]-6-methylpyridin-3-ol

Biological Activity

tmc353121 is a rsv fusion inhibitor. it has been developed from the precursor molecule jnj-2408068 using a molecular modelling approach. it maintains high activity (pec50 9.9) and low cytotoxicity, while presenting a shorter retention time in the lung (lung t1/2 25 h). [1]tmc353121 was found to inhibit rsv by preventing both virus cell fusion and syncytia formation by causing a local disturbance of the natural six-helix bundle conformation of rsv-f protein.tmc353121 reduces viral load in therapeutic and prophylactic administration. tmc353121 has potent antiviral properties in vivo in a balb/c mice model and protects against lung infection and virus-induced inflammation.[2]tmc353121 had dose-dependent antiviral activity, which varied from 1log10 reduction ofpeak viral load to complete inhibition of the rsv replication. tmc353121 (0.39 μg/ml) can completely inhibit the shedding of rsv. and a dose-dependent reduction of infγ, il6 and mip1α was associated. tmc353121 administered as ci for 16 days was generally well-tolerated. [3]

target

RSV

References

1. bonfanti jf, meyer c, doublet f et al. selection of a respiratory syncytial virus fusion inhibitor clinical candidate. 2. discovery of a morpholinopropylaminobenzimidazole derivative (tmc353121). j med chem. 2008; 51: 875–896. 2. olszewska w1, ispas g, schnoeller c et al. antiviral and lung protective activity of a novel respiratory syncytial virus fusion inhibitor in a mouse model. eur respir j. 2011 aug;38(2):401-8.3. ispas g, koul a, verbeeck j et al. antiviral activity of tmc353121, a respiratory syncytial virus (rsv) fusion inhibitor, in a non-human primate model. plos one. 2015 may 26;10(5):e0126959.