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Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
The antiherpes drugs, aciclovir and ganciclovir, are considered the standard treatments and prophylactic agents for infections caused by herpes simplex virus (HSV), varicella zoster virus (VZV) and cytomegalovirus (CMV). Until a decade ago, the impact of aciclovir on the control of severe and life-threatening herpesvirus infections was unprecedented. During the past few years, we have witnessed approval of new therapeutic drugs for infections caused by HSV and VZV (i.e. penciclovir and the oral prodrugs, valaciclovir and famciclovir), CMV (i.e. ganciclovir, cidofovir and fomivirsen) or HSV, VZV and CMV (i.e. foscarnet). A few agents, such as brivudin and benzimidavir, are in ongoing clinical development; others have been suspended because of safety concerns. New antiherpes agents are needed to face clinical issues such as drug resistance, increased use of antiherpes prophylaxis in transplantation and safety concerns in small children or pregnant women.
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Abstract The title compound (IXa) is prepared by reaction of (VI) with the thioimidate (Ic) [obtained in three steps from (II)] to give (VII), followed by treatment with ammonia.
This chapter discusses the Pyran (maleic anhydride divinylether) copolymer and tilorone, 2,7-bis[2-(diethylamino)ethoxy] fluoren-9-one. Following the initial discovery of the interferon inducing properties of pyran copolymer and tilorone, several other synthetic polycarboxylates, related to pyran copolymer, as well as fluorenone ethers, esters, and ketones, related to tilorone, have been described. Various non-nucleotide substances are able to stimulate interferon production in vivo animals and or leukocyte cultures. The spectrum of antiviral activity of poly acrylic acid (PAA) and chlorite-oxidized oxyamylose (COAM) in cell culture has not been analyzed, but the occasional results obtained with PAA and COAM in vitro did not differ markedly from those obtained with polymethacrylic acid PMAA. Thus, Interferon production does not offer a satisfactory explanation for many of the antiviral, antitumoral, and other biological effects demonstrated by polycarboxylates and tilorone in vivo. The observations seem to refute the likelihood that the antiviral, antitumoral, antibacterial, antifungal, and antiprotozoal activities of polycarboxylates and tilorone are mediated by interferon production.
Diazomethane treatment of ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) in the presence of SnCl2 as catalyst led to quantitative formation of the 2'-O-methyl and 3'-O-methyl derivatives of the parent compound. The products were successfully fractionated on a basic ion-exchange column and isolated in crystalline form. Indentification was based on the elution sequence from the column and on 1H NMR spectroscopy. Both derivatives were found to be inactive, relative to the parent compound, against several virus types in cell culture. Unlike ribavirin itself, the 2'(3')-O-methyl derivatives did not suppress cellular DNA synthesis. NMR data showed that the loss of biologic activity upon 2'(3')-O-methylation was not due to a change of conformation of the nucleoside sugar moiety.