Synthesis of new substituted imidazopyridines and evaluation of their anti-HBV activity

Postgraduate Thesis uoadl:2864979 320 Read counter

Unit:
Κατεύθυνση Σχεδιασμός και Ανάπτυξη νέων Φαρμακευτικών Ενώσεων - Φαρμακευτική Χημεία
Library of the School of Science
Deposit date:
2019-03-06
Year:
2019
Author:
Gerasi Maria
Supervisors info:
ΝΙΚΟΛΑΪΣ ΠΟΥΛΗ, ΚΑΘΗΓΗΤΡΙΑ , ΤΜΗΜΑ ΦΑΡΜΑΚΕΥΤΙΚΗΣ, ΕΘΝΙΚΟ ΚΑΙ ΚΑΠΟΔΙΣΤΡΙΑΚΟ ΠΑΜΕΠΙΣΤΗΜΙΟ ΑΘΗΝΩΝ
Original Title:
Σύνθεση νέων υποκατεστημένων ιμιδαζοπυριδινών και αξιολόγηση της δράσης τους έναντι του ιού της ηπατίτιδας Β
Languages:
Greek
Translated title:
Synthesis of new substituted imidazopyridines and evaluation of their anti-HBV activity
Summary:
Hepatitis B virus (HBV) infection is the most common cause of chronic liver disease worldwide. In spite of the availability of safe and effective vaccines, the infection is still a global health problem and proper antiviral treatment is the only way to reduce morbidity and mortality from cirrhosis and hepatocellular carcinoma. Currently, two major classes of agents are utilized in chronic hepatitis B: the interferons and the nucleos(t)ide analogues. However, the approved drugs have several drawbacks that limit their clinical utility. The severe side effects of interferons and the high emergence of HBV drug-resistant strains arising from nucleoside analogues, indicates the clinical need for the discovery of novel classes of antiviral agents for the treatment of hepatitis B. The development of a series of non-nucleoside bezimidazoles provided a promising therapeutic strategy. Among them, compound IIc exhibited high antiviral potency and selectivity index.
In an effort to contribute to the structure-activity relationship studies of these series we have designed and synthesized a number of novel compounds possessing the more purine-like imidazo[4,5-b]pyridine scaffold and investigated their biological activity as potential HBV inhibitors. The new compounds bear different substitution patterns on the fused pyridine ring, while the phthalimide moiety was replaced by alicyclic amines. Furthermore, in order to identify the optimal chain length between the imidazopyridine core and the aminogroup, different alkyl linkers were introduced. Target compounds are also considered the corresponding tosyl derivatives, which were prepared from the tosylation of the heterocyclic base, leading to both 1- and 3-regioisomers of imidazo[4,5-b]pyridine.
Main subject category:
Science
Other subject categories:
Health Sciences
Keywords:
HBV life-cycle, imidazo[4,5-b]pyridine, anti-HBV activity
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
89
Number of pages:
79
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