Journal
ACS MEDICINAL CHEMISTRY LETTERS
Volume 9, Issue 7, Pages 667-672Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsmedchemlett.8b00134
Keywords
Human rhinovirus; capsid-binding; antiviral compound; small molecule inhibitor; oxadiazole
Categories
Funding
- Korea Research Institute of Chemical Technology [KK1703-000, KK1703-E00, KK1803-D00]
- National Research Council of Science & Technology (NST), Republic of Korea [KK1803-D00, KK1703-E00] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
The human rhinovirus (hRV) is the causative agent of the common cold that often aggravates respiratory complications in patients with asthma or chronic obstructive pulmonary disease. The high rate of mutations and variety of serotypes are limiting the development of anti-hRV drugs, which emphasizes the need for the discovery of novel lead compounds. Previously, we identified antiviral compound 1 that we used here as the starting material for developing a novel compound series with high efficacy against hRV-A and -B. Improved metabolic stability was achieved by substituting an ester moiety with a 1,2,4-oxadiazole group. Specifically, compound 3k exhibited a high efficacy against hRV-B14, hRV-A21, and hRV-A71, with EC50 values of 66.0, 22.0, and 3.7 nM, respectively, and a relevant hepatic stability (59.6 and 40.7% compound remaining after 30 min in rat and human liver microsomes, respectively). An in vivo study demonstrated that 3k possessed a desirable pharmacokinetic profile with low systemic clearance (0.158 L.h(-1).Kg(-1)) and modest oral bioavailability (27.8%). Hence, 3k appears to be an interesting candidate for the development of antiviral lead compounds.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available