W0 2011/000721 A1 I||||||||||||||||||||||||||||||||||||||||||||||||||||||||| - Questel

DESCRIPTION
INHIBITORS OF MICROBIAL INFECTIONS
The present invention finds application in the field of medicine and, in
particular, it relates to new inhibitors of microbial infections.
BACKGROUND
Recognition of highly-glycosylated structures displayed at the surface of
several pathogens such as viruses, bacteria, yeasts and parasites appears to
play a key role in the infection process of many pathogens and it is considered
to be an interesting new target for the design of anti-infective agents. At least
for some pathogens, including Human Immunodeficiency Virus (HIV), Dengue
virus, Ebola virus, Hepatitis virus, SARS and Mycobacterium tuberculosis, the
interaction of highly mannosylated glycans with specific lectin receptors in
immune system is an initial and essential step allowing the penetration of the
pathogen within the host cells. Thus, by inhibiting glycans-mediated pathogen
recognition, the initial stages of the infection could be prevented. The anti-
adhesive mechanism by which such antagonists would work interferes with the
pathogenic action of the pathogenic microorganisms, without killing it.
Therapies based on anti-microbial drugs which kill pathogens apply a strong
selective pressure to the microbial population, which in turns favours the
emergence of resistant strains: hence the never-ending search for new, more
powerful agents capable of fighting such strains. For viruses, this is particularly
evident as a consequence of the rapid rate of mutations of viral population. The
approach using anti-adhesive molecules would prevent infection while avoiding
pathogen selective mechanisms, thus simply making the pathogen non
harmful.
It has recently been reported that the pseudo-disaccharide 1 (see below),
mimicking the three-dimensional structure and conformational behavior of a