Supervisors info:
Μαράκος Παναγιώτης, καθηγητής, τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Summary:
Τhe need for the improvement of cure of cancer, a disease that cause many deaths worldwide, has emerged during recent years and the scientific research has focused on the estimation and validation of new molecular targets and the discoveryof novel, more efficient and targeted drugs. The continuous investigation led to the clarification of many mechanisms involved in carcinogenesis and among them, the development of angiogenesis inhibitors is considered as a very promising research field. In the course of an ongoing research project, we have previously identified a series of substituted pyrazolo[3,4-c]pyridines, which influence crucial pro-angiogenic attributes of endothelial cells and exert antitumor activity in mice. The most promising of the previously reported derivatives was used as lead compound for the design and synthesis of a number of structurally related analogues, reported herein. These compounds are 1,3,5,7-tetrasubstituted pyrazolo[3,4-c]pyridines and their synthesis was effected using 2-amino-4-picoline as starting material. This was subjected in successive nitration, diazotation, chlorination, reduction and thermal cyclization and was converted to 5-chloropyrazolo[3,4-c]pyridine. Upon suitable manipulation of the above mentioned intermediate, the appropriate substituents were inserted in the central heterocyclic scaffold. The target compounds were then evaluated as inhibitors of endothelial cell proliferation, with the aim to extract structure-activity relationships, concerning this class of bioactive derivatives.
