Details

Autor(en) / Beteiligte

• Vendeville, Sandrine
• Tahri, Abdellah
• Hu, Lili
• Demin, Samuel
• Cooymans, Ludwig
• Vos, Ann
• Kwanten, Leen
• Van den Berg, Joke
• Battles, Michael B
• McLellan, Jason S
• Koul, Anil
• Raboisson, Pierre
• Roymans, Dirk
• Jonckers, Tim H. M

Titel

Discovery of 3‑({5-Chloro-1-[3-(methylsulfonyl)propyl]‑1H‑indol-2-yl}methyl)-1-(2,2,2-trifluoroethyl)-1,3-dihydro‑2H‑imidazo[4,5‑c]­pyridin-2-one (JNJ-53718678), a Potent and Orally Bioavailable Fusion Inhibitor of Respiratory Syncytial Virus

Ist Teil von

• Journal of medicinal chemistry, 2020-08, Vol.63 (15), p.8046-8058

Ort / Verlag

United States: American Chemical Society

Erscheinungsjahr

2020

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Respiratory syncytial virus (RSV) is a seasonal virus that infects the lungs and airways of 64 million children and adults every year. It is a major cause of acute lower respiratory tract infection and is associated with significant morbidity and mortality. Despite the large medical and economic burden, treatment options for RSV-associated bronchiolitis and pneumonia are limited and mainly consist of supportive care. This publication covers the medicinal chemistry efforts resulting in the identification of JNJ-53718678, an orally bioavailable RSV inhibitor that was shown to be efficacious in a phase 2a challenge study in healthy adult subjects and that is currently being evaluated in hospitalized infants and adults. Cocrystal structures of several new derivatives helped in rationalizing some of the structure–activity relationship (SAR) trends observed.