ACH-126443.: Anti-HBV, Anti-HIV.

Chronic hepatitis B virus (HBV) infection is a major global health concern with an estimated 1-2 million individuals dying every year from hepatitis B-related disease. The goal of treatment for chronic HBV infection is to suppress HBV replication prior to development of irreversible liver damage which ideally would be accomplished with antiviral, agents and immunomodulatory therapy. Over the past 10 years, research has focused on the development of anti-HBV agents able to directly block HBV replication. Naturally occurring nucleoside analogues were used early to treat hepatitis B With little success or high levels of toxicity. The search for novel nucleoside-based chemotherapies continues through modification of the naturally occurring nucleoside-based agents. Of the new generation nucleoside analogues, lamivudine proved to be a potent and well tolerated inhibitor of HBV replication and is clinically available for the treatment of chronic HBV infection. However, long-term treatment with the agent is associated with the development of drug resistance. ACH-126443 is a novel unnatural L-nucleoside reverse transcriptase inhibitor that has shown potent and selective activity against HBV and has also shown significant efficacy against HIV. Due to its promising potent preclinical profile, ACH-126443 was selected for further development as a treatment for chronic HBV and HIV infections.