1259367-01-5Relevant articles and documents
Novel 2-Substituted 7-Azaindole and 7-Azaindazole Analogues as Potential Antiviral Agents for the Treatment of Influenza
Bandarage, Upul K.,Clark, Michael P.,Perola, Emanuele,Gao, Huai,Jacobs, Marc D.,Tsai, Alice,Gillespie, Jeffery,Kennedy, Joseph M.,Maltais, Fran?ois,Ledeboer, Mark W.,Davies, Ioana,Gu, Wenxin,Byrn, Randal A.,Nti Addae, Kwame,Bennett, Hamilton,Leeman, Joshua R.,Jones, Steven M.,O’Brien, Colleen,Memmott, Christine,Bennani, Youssef,Charifson, Paul S.
, p. 261 - 265 (2017/03/08)
JNJ-63623872 (2) is a first-in-class, orally bioavailable compound that offers significant potential for the treatment of pandemic and seasonal influenza. Early lead optimization efforts in our 7-azaindole series focused on 1,3-diaminocyclohexyl amide and urea substitutions on the pyrimidine-7-azaindole motif. In this work, we explored two strategies to eliminate observed aldehyde oxidase (AO)-mediated metabolism at the 2-position of these 7-azaindole analogues. Substitution at the 2-position of the azaindole ring generated somewhat less potent analogues, but reduced AO-mediated metabolism. Incorporation of a ring nitrogen generated 7-azaindazole analogues that were equipotent to the parent 2-H-7-azaindole, but surprisingly, did not appear to improve AO-mediated metabolism. Overall, we identified multiple 2-substituted 7-azaindole analogues with enhanced AO stability and we present data for one such compound (12) that demonstrate a favorable oral pharmacokinetic profile in rodents. These analogues have the potential to be further developed as anti-influenza agents for the treatment of influenza.
INHIBITORS OF INFLUENZA VIRUSES REPLICATION
-
, (2012/06/30)
Methods of inhibiting the replication of influenza viruses in a biological sample or patient, of reducing the amount of influenza viruses in a biological sample or patient, and of treating influenza in a patient, comprises administering to said biological sample or patient an effective amount of a compound represented by Structural Formula (I): or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (I) are as described herein. A compound is represented by Structural Formula (I) or a pharmaceutically acceptable salt thereof, wherein the values of Structural Formula (I) are as described herein. A pharmaceutical composition comprises an effective amount of such a compound or pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, adjuvant or vehicle.
