Pyridine Based Antitumour Compounds Acting at the Colchicine Site.
Antimitotics binding at the colchicine site of tubulin are important antitumour and vascular disrupting agents. Pyridines and azines are privileged scaffolds in medicinal chemistry and in recent years many colchicine site ligands (CSL) have incorporated them into their structures with the aim of improving their pharmacokinetic and pharmacodynamics properties. CSL have been classified according to their chemical structures and the chemical structures of the pyridine and azine containing antimitotic compounds are described. The designed principles behind the structural modifications and the achieved effect on the biological activity upon inclusion of these heterocycles are also discussed. Lessons from the achievements and failures have been extracted and future perspectives delineated.
R
R
Álvarez
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L
Aramburu
P
P
Puebla
E
E
Caballero
M
M
González
A
A
Vicente
M
M
Medarde
Departamento de Química Farmacéutica, Facultad de Farmacia, Campus Miguel de Unamuno s/n, Universidad de Salamanca, Salamanca, 37007, Spain. pelaez@usal.es.
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Peláez
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D003078:Colchicine / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*
D000970:Antineoplastic Agents; D011725:Pyridines; C023666:pyridine; D003078:Colchicine