Long chain N-alkyl compounds and oxa-derivatives thereof

Abstract

Long chain N-alkyl amino and imino compounds, oxa-substituted derivatives thereof, and pharmaceutical compositions including such compounds are described. The long chain N-alkyl group is a C₈-C₁₆ alkyl group. The long chain N-alkyl compounds and oxa-substituted derivatives thereof can be used in the treatment of viral infections, in particular hepatitis B virus or hepatitis C virus, in a cell or an individual. For example, the long chain N-alkyl compounds or oxa-substituted derivatives thereof can be derived from piperidines, pyrrolidines, phenylamines, pyridines, pyrroles, or amino acids.

Description

FIELD OF THE INVENTION[0001]This invention relates to long chain N-alkyl amino and imino compounds and oxa-derivatives thereof for treating pestivirus and flavivirus infections of animals and humans.BACKGROUND OF THE INVENTION[0002]HCV is an RNA virus belonging to the Flaviviridae family. Individual isolates consist of closely related, yet heterologous populations of viral genomes. This genetic diversity enables the virus to escape the host's immune system, leading to a high rate of chronic infection. The flavivirus group to which HCV belongs is known to include the causative agents of numerous human diseases transmitted by arthropod vectors. Human diseases caused by flaviviruses include various hemorrhagic fevers, hepatitis, and encephalitis. Viruses known to cause these diseases in humans have been identified and include, for example, yellow fever virus, dengue viruses 1-4, Japanese encephalitis virus, Murray Valley encephalitis virus, Rocio virus, West Nile fever virus, St. Louis...

AI Technical Summary

Benefits of technology

[0011]In yet another aspect, the invention features a method of treating an individual infected with a virus. The method includes administering an effective amount of the nitrogen-containing virus-inhibiting compound, or a pharmaceutically acceptable salt thereof, to an individual infected with a virus. The treatment can reduce, abate, or diminish the virus infection in the animal or human. The animal can be a bird or mammal (e.g., pig, cow, mice). The nitrogen-containing virus-inhibiting compound can be administered orally.

Problems solved by technology

This genetic diversity enables the virus to escape the host's immune system, leading to a high rate of chronic infection.

Chronic HCV also increases the risk of liver cancer.

Such vaccines have no therapeutic value for those already infected with the virus.

Therapeutic interventions which are effective for treatment of HCV infection are limited in number and effectiveness.

However, interferon-alpha is of limited use in about 20% of the HCV-infected population (Hoofnagle et al., ibid.) and treatment with this compound results in long-term improvement in only 5% of patients.

Furthermore, the complications and limitations of interferon-alpha seriously limit the applicability of the treatment.

The therapy for combined HBV / HCV infection is particularly challenging because the HBV and HCV viruses differ from one another in therapeutically significant ways.

Despite the frequent concurrence of HBV infection and HCV infection, a number of compounds known to be effective for treating HBV infection are not effective against HCV.

For example, lamivudine (the nucleoside analog 3TC) is useful for treating HBV infection, but is not useful for treating HCV infection.

Furthermore, animal viruses can cause significant losses to the livestock industry (Sullivan et al., Virus Res.

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