Synthesis and cytotoxic activity of 2-methylimidazo[1,2-a]pyridine- and quinoline-substituted 2-aminopyrimidine derivatives.
A 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.
Vilchis-Reyes
Miguel Angel
MA
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, México 04510, D. F., México. vilchis90@yahoo.com
Zentella
Alejandro
A
Martínez-Urbina
Miguel Angel
MA
Guzmán
Angel
A
Vargas
Omar
O
Ramírez Apan
María Teresa
MT
Ventura Gallegos
José Luis
JL
Díaz
Eduardo
E
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D011725:Pyridines / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry*
D000970:Antineoplastic Agents; D011725:Pyridines; D011743:Pyrimidines; D011804:Quinolines; C012180:2-aminopyrimidine; C037219:quinoline; D018844:Cyclin-Dependent Kinases; C023666:pyridine