Antiviral compounds

Several synthetic pyrimidines and purines are useful drugs Acyclovir was the first effective antiviral compound and is used to treat herpes infections 6 Mercaptopunne is one of the drugs used to treat childhood leukemia which has become a very treatable form of cancer with a cure rate approaching 80%... 

P-(P -D-aiabinofuianosyl)-9ff-puiin-6-amine] [5536-17 ], an antineoplastic and antiviral compound known by a number of trade names, and AZT (3 -azido-3 -deoxythymidine [30516-87-1]) an antiviral compound also known by a variety of trade names (see Antiviral agents). 

Viral infections continue to be significant causes of morbidity and mortality and at the same time continue to be resistant to treatment by small molecules. Avridine (6) is an antiviral compound which has shown some activity in a variety of animal tests apparently based upon its ability to stimulate a number of cells to produce the high molecular weight endogenous antiviral substance interferon. Thus, the compound is believed to operate indirectly by stimulating the body s own natural defenses against viral penetration into host cells. Avridine is synthesized by... 

Approaches for the Development of Antiviral Compounds The Case of Hepatitis C Virus... 

Since the pioneering work of Kleymann et al. (2002), Betz et al. (2002), Baumeister et al. (2007), and Crute et al. (2002), who showed that compounds identified as inhibitors of the helicase-primase enzyme complex could alleviate herpesvirus-induced disease in animal models, the attention of researchers developing antiviral compounds has been drawn more and more towards the virus-encoded helicases, particularly those of Herpes viruses and of RNA viruses such as Hepatitis C Virus (HCV) and SAKS coronavirus (SARS-CoV). Enzyme activity is usually assayed by measuring NTPase activity in the presence of an appropriate nucleic acid co-substrate although, more recently, novel fiuorimetric and luminescence principles have been applied to the measurement of strand unwinding and/or translocation of the protein along the nucleic acid (Frick 2003, 2006). 

Virus maturation and assembly at the cell membrane or the nuclear membrane has long been seen as a potential target for antiviral compounds. For the virus to mature and be released in a conformation that will insure stability and survival of the viral genome in the exttacellular enviromnent, the protein subunits of the capsid or nucle-ocapsids have to be transported to the assembly point where they will form the final particles around the viral nucleic acid. If this process does not occur in an orderly and programmed manner, the capsid subunits will not form the required multimers and the viral components will become targets for the cellular disposal mechanisms. 

To further improve sustained virologic response rates, different treatment approaches are currently under investigation. For example, individualized therapy durations on the basis of the HCV RNA concentration at baseline and early during therapy are the subject of clinical studies (Berg et al. 2006 Zeuzem et al. 2005a). In addition, triple therapy with other antiviral compounds, such as amantadine, has been evaluated in multiple studies, leading to contradictory results (Mangia et al. 2004). 

Complex imide 169 was prepared during an investigation into the preparation of analogues of the antiviral compound zanamivir Cyclization of imide 169 in acidic media, followed by treatment with trifluoroacetic acid, gave the corresponding 1,2,4-triazole 170 in a yield that was reported to be high (Equation 54) <1997BML2239>. 

The neuramidase inhibitor oseltamivir phosphate was discovered by Gilead Sciences and developed by Roche Pharmaceuticals under the name of Tamiflu (Scheme 5.13) to be used as an orally active antiviral compound for prevention and treatment of influenza infections. Because of the recent emergence of the avian flu, the demand for Tamiflu has gained momentum. Two industrially feasible syntheses are known, starting from (—)-shikimic acid and (—)-quinic acid, respectively (Scheme 5.13) [45]. 

The rapid identification of anti-HIV compounds in the laboratory following the isolation of the causative virus in 1983 and their subsequent use in treatment was not unexpected. Three decades of previous work has established a scientific basis for the evaluation of antiviral compounds. However, no antiviral yet discovered can cause total blockade of a virus replicating in a cell. The combination of properties of HIV, including latency and antigenic and biochemical variation, is unusual, and the virus represents a daunting challenge for chemotherapy. 

A whole family of 2, 3 -dideoxynucleoside exists, and it is apparent that they may vary considerably in their antiviral and anticellular activities. Removal of the oxygen at the 3 carbon of the sugar of 2 -deoxyadenosine changes the molecule into a powerful antiviral compound, 2, 3 -dideoxyadenosine. 

AZT, which is an antiviral compound against HIV, is an effective drug in AIDS patients. The fact that this drug works means that agents that interfere with continued HIV infection in an AIDS patient will improve the clinical status. 

Thus, great efforts are being made to develop other antiviral compounds that will also block HIV infection. Ultimately, it may be possible to use several antivirals in combination that completely block the spread of HIV infection in an individual. 

An attractive option for the development of antiviral compounds is to prevent viral entry. These entry inhibitors interfere at an early stage of infection, which has several advantages. The number of infectious particles is rather small, and therefore entry inhibitors should be very effective if applied at the right time, even at lower doses [2]. In addition, many of the problems associated with delivering a drug into cells are avoided as the interference takes place outside the cell. 

The key objective of our efforts has been to develop a vaginal formulation that optimizes spermicidal and antiviral activity while enhancing spreading and true bioadhesiveness. Utilization of strict design principles for an excipient delivery vehicle, which included substantivity to vaginal mucosa, saline compatibility, compatibility with a wide range of spermicidal and antiviral compounds, low irritation potential, sperm impedance, system stability, and efficacy after stressed storage conditions, resulted in the development of DCE s [11,12,13]. Based on the results from in vitro studies, the DCE vehicle was selected for clinical development. 

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