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
| العنوان: | 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 |
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| المؤلفون: | Jason S. McLellan, Tim H. M. Jonckers, Sandrine Marie Hele Vendeville, Anil Koul, Dirk Roymans, Abdellah Tahri, Samuel Demin, Leen Kwanten, Joke Van Den Berg, Lili Hu, Pierre Raboisson, Ludwig Cooymans, Michael B. Battles, Ann Vos |
| المصدر: | Journal of Medicinal Chemistry. 63:8046-8058 |
| بيانات النشر: | American Chemical Society (ACS), 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0303 health sciences, Chemistry, Fusion inhibitor, Treatment options, Pharmacology, medicine.disease, 01 natural sciences, Virus, 0104 chemical sciences, Bioavailability, 010404 medicinal & biomolecular chemistry, 03 medical and health sciences, Pneumonia, Bronchiolitis, Drug Discovery, Acute lower respiratory tract infection, medicine, Molecular Medicine, Respiratory system, 030304 developmental biology |
| الوصف: | 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. |
| تدمد: | 1520-4804 0022-2623 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::45fd2adb6b7e38092df92344e7c293c0 https://doi.org/10.1021/acs.jmedchem.0c00226 |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi...........45fd2adb6b7e38092df92344e7c293c0 |
| قاعدة البيانات: | OpenAIRE |
Find this issue from the American Chemical Society | تدمد: | 15204804 00222623 |
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