Σχεδιασμός και Σύνθεση Νέων Αμινοϋποκατεστημένων Πυραζολο[3,4-c]πυριδινών, ως Πιθανών Αναστολέων Πρωτεϊνικών Κινασών

Postgraduate Thesis uoadl:1320242 549 Read counter

Unit:
ΠΜΣ με ειδίκευση ΣΥΝΘΕΤΙΚΗ ΦΑΡΜΑΚΕΥΤΙΚΗ ΧΗΜΕΙΑ
Library of the School of Science
Deposit date:
2012-03-06
Year:
2012
Author:
Σκλεπάρη Μερόπη
Supervisors info:
Παναγιώτης Μαράκος Καθηγ. ΕΚΠΑ
Original Title:
Σχεδιασμός και Σύνθεση Νέων Αμινοϋποκατεστημένων Πυραζολο[3,4-c]πυριδινών, ως Πιθανών Αναστολέων Πρωτεϊνικών Κινασών
Languages:
Greek
Summary:
Nowadays, cancer is regarded responsible for many deaths and one of the most
common diseases in the present world. During the last years, the need for the
improvement of the cure of cancer emerged and the scientific research has
focused on the estimation of molecular targets and on the prediction of the
structure of potential drugs. The continuous investigation led to the knowledge
of some of the various mechanisms of carcinogenesis and as a result, to the
idea of developing pharmacological inhibitors of kinases as very promising
targets. Kinases are enzymes that control cell cycle via protein
biophosphorylation, an important reaction in the post translational regulation
of enzymes and structural proteins. Abnormal activation of kinases or absence
of their naturally occurring inhibitors results in many human disorders and
even to the loss of control of cell proliferation. A number of diverse classes
of kinase inhibitors have been reported at the present and many of them have
derived from the purine scaffold, like the established inhibitors of cyclin
depended kinases olomoucine, roscovitine and purvalanol A and B.
Based on the above mentioned considerations we describe in this study the
design and synthesis of some new substituted pyrazolo[3,4-c]pyridines, which
can be regarded as the 8-aza-3,9-deazapurine condensed heterocyclic system. As
a result, the derivatives that were synthesized, possess a methyl group or no
group at the position 1, a 5-aryl or alkylamine side chain, as well as a
variety of 3-aminoalkyl substituents. The compounds were prepared using
2-amino-4-picoline as starting material, which after a series of reactions led
to 3-acetamido-6-chloro-4-picoline which through diazotation, ring closure and
nitration provided the corresponding
5-chloro-3-nitro-1H-pyrazolo[3,4-c]pyridine. This analogue was used as a common
intermediate which upon substitution, reduction and chloroacetylation provided
the route for the synthesis of the aminosubstituted target derivatives. The aim
of the project is to study the new derivatives against a panel of kinases and
extract structure activity relationships concerning this scaffold.
Keywords:
Pyrazolo[3, 4-c]pyridines, Protein kinases , Purine analogues
Index:
No
Number of index pages:
0
Contains images:
Yes
Number of references:
58
Number of pages:
59
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