ABSTRACT
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.
Subject(s)
Anticoagulants/pharmacology , Enzyme Inhibitors/pharmacology , Monophenol Monooxygenase/antagonists & inhibitors , Pyrans/pharmacology , Pyrimidines/pharmacology , Triazoles/pharmacology , Agaricus/enzymology , Anticoagulants/blood , Anticoagulants/chemical synthesis , Anticoagulants/chemistry , Binding Sites , Enzyme Inhibitors/blood , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Molecular Docking Simulation , Molecular Structure , Monophenol Monooxygenase/chemistry , Partial Thromboplastin Time , Pyrans/blood , Pyrans/chemical synthesis , Pyrans/chemistry , Pyrimidines/blood , Pyrimidines/chemical synthesis , Pyrimidines/chemistry , Structure-Activity Relationship , Triazoles/blood , Triazoles/chemical synthesis , Triazoles/chemistryABSTRACT
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.