1353628-13-3Relevant articles and documents
Discovery of an oral respiratory syncytial virus (RSV) fusion inhibitor (GS-5806) and clinical proof of concept in a human RSV challenge study
Mackman, Richard L.,Sangi, Michael,Sperandio, David,Parrish, Jay P.,Eisenberg, Eugene,Perron, Michel,Hui, Hon,Zhang, Lijun,Siegel, Dustin,Yang, Hai,Saunders, Oliver,Boojamra, Constantine,Lee, Gary,Samuel, Dharmaraj,Babaoglu, Kerim,Carey, Anne,Gilbert, Brian E.,Piedra, Pedro A.,Strickley, Robert,Iwata, Quynh,Hayes, Jaclyn,Stray, Kirsten,Kinkade, April,Theodore, Dorothy,Jordan, Robert,Desai, Manoj,Cihlar, Tomas
supporting information, p. 1630 - 1643 (2015/04/27)
GS-5806 is a novel, orally bioavailable RSV fusion inhibitor discovered following a lead optimization campaign on a screening hit. The oral absorption properties were optimized by converting to the pyrazolo[1,5-a]-pyrimidine heterocycle, while potency, metabolic, and physicochemical properties were optimized by introducing the para-chloro and aminopyrrolidine groups. A mean EC50 = 0.43 nM was found toward a panel of 75 RSV A and B clinical isolates and dose-dependent antiviral efficacy in the cotton rat model of RSV infection. Oral bioavailability in preclinical species ranged from 46 to 100%, with evidence of efficient penetration into lung tissue. In healthy human volunteers experimentally infected with RSV, a potent antiviral effect was observed with a mean 4.2 log10 reduction in peak viral load and a significant reduction in disease severity compared to placebo. In conclusion, a potent, once daily, oral RSV fusion inhibitor with the potential to treat RSV infection in infants and adults is reported.
PYRAZOLO [1, 5 -A] PYRIMIDINES AS ANTIVIRAL AGENTS
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Page/Page column 158-159, (2012/01/14)
The invention provides compounds of Formula I or Formula II: (I), (II) or a pharmaceutically acceptable salt or ester, thereof, as described herein. The compounds and compositions thereof are useful for treating Pneumovirinae virus infections. The compounds, compositions, and methods provided are particularly useful for the treatment of Human respiratory syncytial virus infections.
