RESUMO
Pyrimidine-fused compounds are of great interest for the discovery of potent bioactive agents. This study describes the synthesis of novel pyranopyrimidines 3a-f and pyranotriazolopyrimidines 4a-d derivatives via the cyclocondensation reaction of α-functionalized iminoether 2, which was obtained from 2-amino-3-cyanopyrane 1, with a series of primary aromatic amines and hydrazides, respectively. Structures of all synthesized compounds were established on the basis of spectroscopic methods including 1H NMR, 13C NMR and ES-HRMS. They were finally tested for their anticoagulant and anti-tyrosinase activities. Significant results have been obtained and the structure-activity relationship (SAR) was discussed with the help of molecular docking analysis.
Assuntos
Anticoagulantes/farmacologia , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Piranos/farmacologia , Pirimidinas/farmacologia , Triazóis/farmacologia , Agaricus/enzimologia , Anticoagulantes/sangue , Anticoagulantes/síntese química , Anticoagulantes/química , Sítios de Ligação , Inibidores Enzimáticos/sangue , Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/química , Humanos , Simulação de Acoplamento Molecular , Estrutura Molecular , Monofenol Mono-Oxigenase/química , Tempo de Tromboplastina Parcial , Piranos/sangue , Piranos/síntese química , Piranos/química , Pirimidinas/sangue , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade , Triazóis/sangue , Triazóis/síntese química , Triazóis/químicaRESUMO
A series of new 1,2,3-triazole linked coumarinopyrazole conjugates 4a-e and 5a-e have been synthesized via the Copper(I)-catalysed Alkyne-Azide Cycloaddition (CuAAC). Going through the reaction of compound 2 with the 3-propargyl bromide gave a mixture of propargylated regioisomers 3â¯+â¯3' used as a dipolarophile to access to triazoles 4a-e and 5a-e. The structures of the prepared cycloadducts were determined by 1H, 13C and 2D-NMR techniques and by HRMS analysis. All the synthesized derivatives have been evaluated for their anticholinesterase, anti-5-lipoxygenase, anti-tyrosinase, and cytotoxic activities.