Nowadays tuberculosis is one of the most widely spread diseases, which annually takes 2
million human lives worldwide. The number of new cases is drastically rising and will
soon reach 10 million according to the World Health Organisation. To make it worse the
emergence of drug resistant strains of Mycobacterium tuberculosis to current regimen
makes the researching for novel drugs an urgent priority. More and more publications
about antitubercular drugs come from originator pharmaceutical companies that are aware
of the severity of the situation.
Department for Pharmaceutical Chemistry from Faculty of Pharmacy, University of
Ljubljana participates in the development of new antitubercular drugs in the European
project »Open Collaborative Model of Tuberculosis Lead Optimisation« (acronime
»ORCHID«) with Madrid laboratory Tres Cantos Medicines Development Campus of
GlaxoSmithKline company. The latter developed derivatives of thiazolo[4,5-c]quinolines
and some of them were very effective against Mycobacterium tuberculosis strains.
Unfortunately, all of them showed tendency toward poor solubility in water
During thesis we have tried to synthesize new analogues of a lead compound aiming to
retaining or improving antimicobacterial activity and improve water solubility, which will
further lead to greater extent of absorption and bioavailability. We synthesized two
compounds, which both had a common thiazolo[4,5-c]quinoline scaffold, the only
differences were the substituents at place 6 in quinoline and place 2' in thiazolo ring. In the
synthesis of the first final compound we used p-nitrophenylacetic acid, which in our
opinion may improve the antimicobacterial activity but not the pharmacokinetic properties.
BOC-phenylglycin was used to synthesize the second final compound. We think it might
possess an equal or better antitubercular activity and contribute to superior
pharmacokinetic properties. Because of the missing chlorine atom at the place 6 this
compound might slightly differ in its potency and antibacterial spectrum. Synthesis of the
third final compound with 2-amino-4-thiazoloacetic acid never could not be accomplished
because we have run out of the parent compound. Both final compounds will be further
evaluated for antimicobacterial activity.