Miguel Angel Vilchis-Reyes, Alejandro Zentella, Miguel Angel Martínez-Urbina, Angel Guzmán, Omar Vargas, María Teresa Ramírez Apan, José Luis Ventura Gallegos, Eduardo Díaz
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, México 04510, D. F., México. vilchis90@yahoo.com
European journal of medicinal chemistry 2010 JanA series of 2-methylimidazo[1,2-a]pyridine- and quinoline-substituted 2-aminopyrimidines derivatives were synthesized using a convenient synthetic route. We evaluate the isosteric replacement of methyl groups in 4-(2-methylimidazo[1,2-a]pyridin-3-yl)-N-p-tolylpyrimidin-2-amine (compound 1) by trifluoromethyl groups and the isosteric substitution of the 2-methylimidazo[1,2-a]pyridin-3-yl scaffold by quinolin-4-yl or quinolin-3-yl moieties. The replacement of hydrogen by fluorine does not affect notably the cytotoxic activity and CDK inhibitor activity in this series. Quinolin-4-yl-substituted compound, 8, presents cytotoxic activity and is most effective and selective against CDK1/CycA than against CDK2/CycB. Compound 11, which has a quinolin-3-yl moiety is CDK inhibitor but presents null cytotoxic activity. Quinolin-4-yl-substituted compounds constitute a new lead of cytotoxic and CDK inhibitor compounds from which more compelling and selective inhibitors can be designed. Copyright 2009 Elsevier Masson SAS. All rights reserved.
Miguel Angel Vilchis-Reyes, Alejandro Zentella, Miguel Angel Martínez-Urbina, Angel Guzmán, Omar Vargas, María Teresa Ramírez Apan, José Luis Ventura Gallegos, Eduardo Díaz. Synthesis and cytotoxic activity of 2-methylimidazo[1,2-a]pyridine- and quinoline-substituted 2-aminopyrimidine derivatives. European journal of medicinal chemistry. 2010 Jan;45(1):379-86
PMID: 19879023
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