New treatments for genital herpes

Abstract

Genital herpes is a sexually transmitted disease that has been widely investigated from both an epidemiological and a diagnostic viewpoint. Better knowledge of the disease has pointed to the important role of asymptomatic herpes simplex virus type 2 shedding as a major culprit for the spread of the virus in the world, the latest statistics showing that the incidence of genital herpes is constantly increasing. The reference compound for the treatment and prophylaxis of genital herpes is acyclovir. Recently, two drugs with better oral bioavailability, valaciclovir, the oral prodrug of acyclovir, and famciclovir, the oral prodrug of penciclovir, have been made available. Nevertheless, there is a need to develop additional approaches, to extend the therapeutic possibilities and to face the problem of emerging resistant viruses, mostly in immunocompromised patients. Therefore, efforts have been made in different directions including the exploration of new targets for antiviral chemotherapy, the use of immunomodulators and the development of specific vaccines.

Synthesis, antimicrobial and antiviral evaluation of substituted imidazole derivatives

“…In continuation with our research program concerning the synthesis and antimicrobial evaluation of medicinally important compounds [25][26][27][28][29][30][31][32][33], in the present study we have synthesized 2-(substituted phenyl)-1H-imidazoles (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12). Further recent literature revealed that N 1 -substitution of imidazoles improves the antibacterial activity [34].…”

“…5.1. General procedure for the synthesis of 2-(substituted phenyl)-1H-imidazoles (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) Substituted anilines (0.13 mol) in hydrochloric acid/water mixture (1:1) were diazotized using solution of sodium nitrite at 0-10 C. To the diazotized mixture, imidazole (0.004 mol) was added with vigorous shaking. A solution of sodium acetate (40 g in 100 ml) was added dropwise to the above mixture by maintaining the temperature at 5-10 C. The above solution was stirred initially for 3 h at cold condition followed by continuation of stirring at room temperature for 48 h. The product obtained was filtered, dried and recrystallized from alcohol.…”

“…Compounds 1-12 are the key intermediates for the synthesis of compounds 13-26. The key intermediates, 2-(substituted phenyl)-1H-imidazoles (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), were prepared by the condensation of imidazoles with corresponding substituted aryldiazonium chlorides which in turn were prepared by the diazotization of substituted anilines. However, based on our experience, the application of cupric chloride to the condensation of aryldiazonium chloride with benzimidazole as suggested by Dahiya and Pathak [35] resulted in resinous products.…”

“…Therefore, coupling was carried out using sodium acetate along with stirring in cold conditions for the initial 3 h followed by 48 h stirring at room temperature which resulted in a solid product. For the synthesis of (substituted phenyl)-[2-(substituted phenyl)-imidazol-1-yl]-methanones (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26), the key intermediates (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12) were reacted with substituted benzoyl chloride which was prepared by the reaction of substituted benzoic acid with thionyl chloride. The physicochemical characteristics of the synthesized compounds are presented in Table 1.…”

“…Recently, immunomodulators (imiquimod and resiquimod), nonnucleoside viral polymerase inhibitors (4-hydroxyquinoline-3-carboxamides), and viral helicase inhibitors (thiazolylphenyl and thiazolylamide) have received considerable attention. Though numerous strategies and considerable efforts have been spent in search of the next generation antiviral therapy, it has proved difficult to outperform acyclovir [6,10].…”