Summary:
Cell division, a process which is instrumental to the development and
progression of tumors, has been an attractive target for antitumor therapy. In
normal cells the mitotic process is under heavy post-translational control by
several regulatory mechanisms, concerning protein localization, proteolysis and
phosphorylation performed by a number of serine/threonine mitotic kinases.
Mitotic entry and exit as well as many other key events associated with
mitosis, are brought about by the activation of kinases. A protein kinase is an
enzyme that modifies other proteins by chemically adding phosphate groups to
them, a process which is called phosphorylation.Phosphorylation usually results
in a functional change of the target protein (substrate) by changing enzyme
activity, cellular location or association with other proteins.Cancer cells in
contrast, are often characterized by the loss of control of important
regulatory cell cycle checkpoints, and the incorrect segregation of chromosomes
during mitosis results in aneuploidy and chromosome instability. Amplification
of several mitotic kinase genes are frequently observed in human tumors.
Determining the functions of kinases is currently an active area of research
and a great deal of investigations is directed towards identifying selective
kinase inhibitors as anticancer agents. Taking into account that many
purine-like heterocyclic systems have shown interesting activities against
mitotic kinases and in the course of a research project aimed to develop novel
kinase inhibitors, we have designed some Cell division, a process which is
instrumental to the development and progression of tumors, has been an
attractive target for antitumor therapy. In normal cells the mitotic process is
under heavy post-translational control by several regulatory mechanisms,
concerning protein localization, proteolysis and phosphorylation performed by a
number of serine/threonine mitotic kinases. Mitotic entry and exit as well as
many other key events associated with mitosis, are brought about by the
activation of kinases. A protein kinase is an enzyme that modifies other
proteins by chemically adding phosphate groups to them, a process which is
called phosphorylation.Phosphorylation usually results in a functional change
of the target protein (substrate) by changing enzyme activity, cellular
location or association with other proteins.Cancer cells in contrast, are often
characterized by the loss of control of important regulatory cell cycle
checkpoints, and the incorrect segregation of chromosomes during mitosis
results in aneuploidy and chromosome instability. Amplification of several
mitotic kinase genes are frequently observed in human tumors. Determining the
functions of kinases is currently an active area of research and a great deal
of investigations is directed towards identifying selective kinase inhibitors
as anticancer agents. Taking into account that many purine-like heterocyclic
systems have shown interesting activities against mitotic kinases and in the
course of a research project aimed to develop novel kinase inhibitors, we have
designed
new substituted pyrazolo[3,4-d]pyridazines with the following general formulas
(R1: aliphatic or aromatic amine, R2: aryl, alkyl, R3: H, CH3, CH2C5H6), with
the aim to investigate their potential kinase inhibitory activities.
Keywords:
Tumor, Inhibitors, Pyrazolopyridazines, Protein, Kinases
