Synthesis and biological profiling of 6- or 7-(het)aryl-7-deazapurine 4'-C-methylribonucleosides.

The synthesis and biological activity profiling of a large series of diverse pyrrolo[2,3-d]pyrimidine 4'-C-methylribonucleosides bearing an (het)aryl group at position 4 or 5 is reported as well as the synthesis of several phosphoramidate prodrugs. These compounds are 4'-C-methyl derivatives of previously reported cytostatic hetaryl-7-deazapurine ribonucleosides. The synthesis is based on glycosylation of halogenated 7-deazapurine bases with 1,2-di-O-acetyl-3,5-di-O-benzyl-4-C-methyl-ß-d-ribofuranose followed by cross-coupling and nucleophilic substitution reactions. The final compounds showed low cytotoxicity and several derivatives exerted antiviral activity against HCV or Dengue viruses at micromolar concentrations.

Hepatitis B virus therapy: What's the future holding for us?

Hepatitis B is one of the leading causes of liver cancer worldwide and unfortunately the number of people affected with hepatitis B virus (HBV) infection is still on the rise. Although the HBV has been known to cause fatal illness since decades but the population effected by this lethal virus have still only a few options for its management. The major treatment strategies include interferons and nucleos(t)ide analogues. These agents have so far produced unsatisfactory results in terms of complete virus eradication. Interferons cannot be used for long term therapy because of their potential side effects. Prolong treatment with nucleos(t)ide analogues has also been reported to cause serious side effects besides the increasing resistance by the virus. The need for new innovative solutions for treatment of HBV has been realized by global research institutes and pharmaceutical industry. Present review focuses in detail on the new ideas that are being transformed into therapeutic tools for use as future therapies in HBV infection. Modern drug designing and screening methods have made the drug discovery process shorter and more reliable. HBV therapeutics will take a new turn in coming years owing to these intelligent drug designing and screening methods. Future therapy of HBV is aiming to include the use of vaccines (both prophylactic and therapeutic), immunomodulators such as antibodies, non-nucleoside antivirals such as RNAi and inhibitors of viral life cycle.

Emerging antivirals for the treatment of hepatitis B.

Chronic infection with hepatitis B virus (HBV) constitutes a major global public health threat, causing substantial disease burdens such as liver cirrhosis and hepatocellular carcinoma, thus representing high unmet medical needs. Currently available therapies are safe, well tolerated, and highly effective in decreasing viremia and improving measured clinical outcomes with low rates of antiviral resistance. However, long-term management remains a clinical challenge, mainly due to the slow kinetics of HBV surface antigen clearance. In this article, we review emerging antivirals directed at novel targets derived from mechanisms of viral cellular entry, viral replication, viral assembly, and the host immune response, leading to preclinical and clinical trials for possible future therapeutic intervention. The recent therapeutic advances in the development of all categories of HBV inhibitors may pave the way for regimens of finite duration that result in long-lasting control of chronic hepatitis B infection.