The vast majority of the world population is infected with at least one member of the human herpesvirus family. Herpes simplex virus (HSV) infections are the cause of cold sores and genital herpes as well as life-threatening or sight-impairing disease mainly in immunocompromized patients, pregnant women and newborns. Since the milestone development in the late 1970s of acyclovir (Zovirax), a nucleosidic inhibitor of the herpes DNA polymerase, no new non-nucleosidic anti-herpes drugs have been introduced. Here we report new inhibitors of the HSV helicase-primase with potent in vitro anti-herpes activity, a novel mechanism of action, a low resistance rate and superior efficacy against HSV in animal models. BAY 57-1293 (N-[5-(aminosulfonyl)-4-methyl-1,3-thiazol-2-yl]-N-methyl-2-[4-(2-pyridinyl)phenyl]acetamide), a well-tolerated member of this class of compounds, significantly reduces time to healing, prevents rebound of disease after cessation of treatment and, most importantly, reduces frequency and severity of recurrent disease. Thus, this class of drugs has significant potential for the treatment of HSV disease in humans, including those resistant to current medications.

Es wird eine neue Methode zur selektiven Synthese von Oligosacchariden mit P-verknupfter Mannose-Einheit entwickelt, fur deren direkte Gewinnung es bisher kein Verfahren gab. Als Katalysator dient ein auf A1203 niedergeschlagenes Silbersilicat. Es werden die Trisaccharide S-D- Building Units for Oligosaccharides, X X X *) New Efficient 0-Glycoside Synthesis of Mannose Glycosides Syntheses of Mannose Containing Oligosaccharides A new method was developed for the stereo selective synthesis of oligosaccharides containing a P-linked mannose-unit which were hitherto not available by direct synthesis. The glycoside synthesis is promoted by a silversilicate-catalyst which was precipitated on aluminium oxide. The trisaccharides 20 and 31 (see german summary) and the tetrasaccharide 33 were synthesized, demonstrating the advantages offered by block synthesis.In der repeating-unit der 0-antigenen Kette des Lipopolysaccharides aus Escherichia coli 0 75, dessen Synthese wir geplant haben, und von der schon einige von uns synthetisierte Teilstrukturen vorliegen'), ist eine Mannose-Einheit in fbglycosidischer Bindung enthalten. Die repeating-unit besitzt die folgende Formel*):Es ist zu ersehen, daB die Mannose-Einheit B(1 + 4)-glycosidisch an die D-Galactose am Verzweigungspunkt der Oligosaccharidkette gebunden ist. Die Herstellung derarti-

Although the most successful vaccines still consist of attenuated or killed pathogens, it is evident that genetic engineering will eventually provide pure antigens in sufficient quantities. To achieve a protective effect, however, the immune response to these structures, which are only weakly immunogenic, must be activated by adjuvants. The discovery of chemically defined, well-tolerated. synthetic adjuvants is therefore especially important in effective immunoprophylaxis. A very promising class of compounds in this respect are synthetic glycosylamides, with two long alkyl chains consisting of alkylamines and fatty acids. Unlike natural glycolipids, which exert an immunosuppressive effect, the new glycolipid analogues described here show marked immunostimulation. In vaccination experiments with various antigens they provide efficient protection. Their mode of action, which differs from that of known adjuvants, makes glycolipid analogues particularly interesting for immunization of patients with defective T lymphocyte function, for example AIDS patients.

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