RESUMEN
This work describes the utility of pyrazole-4-carbaldehyde 1 as starting material for the synthesis of a novel potent series of 5α-reductase and aromatase inhibitors derived from 1,2,3-triazole derivative. Condensation of 1 with active methylene and different amino pyrazoles produced the respective Schiff bases 2-4, 8 and 9. On the other hand, 1 was reacted with ethyl cyanoacetate and thiourea in one-pot reaction to afford the pyrazolo-6- thioxopyridin-2-[3H]-one (10). Moreover, α-ß unsaturated chalcone derivative 11 was prepared via the reaction of compound 1 with P-methoxy acetophenone, which in turn reacted with each of ethyl cyanoacetate, malononitrile, hydrazine hydrate, and thiosemicarbazide to afford the corresponding pyridine and pyrazole derivatives 13, 14, 17, and 20. The structure of newly synthesized compounds was characterized by analytical and spectroscopic data (IR, MS and NMR). All new compounds were evaluated against 5α-reductase and aromatase inhibitors and the results showed that many of these compounds inhibit 5α-reductase and aromatase activity; compound 13 was found to be the highest potency among the tested samples comparing with the reference drugs.
Asunto(s)
Inhibidores de 5-alfa-Reductasa/síntesis química , Inhibidores de 5-alfa-Reductasa/farmacología , Inhibidores de la Aromatasa/síntesis química , Inhibidores de la Aromatasa/farmacología , Triazoles/química , Inhibidores de 5-alfa-Reductasa/química , Animales , Antibacterianos/síntesis química , Antibacterianos/química , Antineoplásicos/síntesis química , Antineoplásicos/química , Antivirales/síntesis química , Antivirales/química , Aromatasa/efectos de los fármacos , Inhibidores de la Aromatasa/química , Colestenona 5 alfa-Reductasa/efectos de los fármacos , Dihidrotestosterona/sangre , Letrozol/farmacología , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Testosterona/sangreRESUMEN
The reaction of 5-amino-3-(arylamino)-1H-pyrazole-4-carboxamides 1a,b with acetylacetone 2 and arylidenemalononitriles 5a-c yielded the pyrazolo[1,5-a]-pyrimidine derivatives 4a,b and 7a-f respectively. On the other hand, Schiff bases 9a,b and 12a-j were obtained upon treatment of carboxamides 1a,b with isatin 8 and some selected aldehydes 11a-e. The newly synthesized compounds were characterized by analytical and spectroscopic data. Representative examples of the synthesized products 4a,b, 7e, 7f, 9b, 12b-f, 12h, and 12j were screened for their in vitro antitumor activities against different human cancer cell lines and the structure-activity relationship (SAR) was discussed.
