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4-Oxooctahydroquinoline-1(2H)-carboxamides as hepatitis B virus (HBV) capsid core protein assembly modulators
Journal article   Open access   Peer reviewed

4-Oxooctahydroquinoline-1(2H)-carboxamides as hepatitis B virus (HBV) capsid core protein assembly modulators

Nicky Hwang, Haiqun Ban, Shuo Wu, Kelly McGuire, Ellen Hernandez, Junjun Chen, Qiong Zhao, Manasa Suresh, Benjamin Blass, Usha Viswanathan, …
Bioorganic & medicinal chemistry letters, v 58, pp 128518-128518
15 Feb 2022
PMID: 34979256
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8792325View
Accepted (AM)Open Access (License Unspecified) Open

Abstract

Chemistry Chemistry, Medicinal Chemistry, Organic Life Sciences & Biomedicine Pharmacology & Pharmacy Physical Sciences Science & Technology
Hepatitis B virus (HBV) core protein, the building block of the HBV capsid, plays multiple roles in viral replication, and is an attractive target for development of antiviral agents with a new mechanism of action. In addition to the heteroaryldihydropyrimidines (HAPs), sulfamoylbenzamides (SBAs), dibenzothiazepine derivatives (DBTs), and sulfamoylpyrrolamides (SPAs) that inhibit HBV replication by modulation of viral capsid assembly and are currently under clinical trials for the treatment of chronic hepatitis B (CHB), other chemical structures with activity to modulate HBV capsid assembly have also been explored. Here we describe our continued optimization of a benzamide originating from our high throughput screening. A new bicyclic carboxamide lead featuring an electron deficient non-planar core structure was discovered. Evaluations of its ADMET (absorption, distribution, metabolism, excretion and toxicity) and pharmacokinetic (PK) profiles demonstrate improved metabolic stability and good bioavailability.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Chemistry, Medicinal
Chemistry, Organic
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