[摘要]：New phthalazine-based vasodilators were synthesized through the chloroacylation of the starting compound 1-hydrazinophthalazine 4 to give the two key intermediates 5 and 7. These intermediates were used to alkylate various cyclic amines to furnish the final compounds 6a-h and 8a-h. Compounds were tested for their vasorelaxant activities against nor-adrenaline-induced spasm on thoracic rat aorta rings and compared to the reference drug, prazosin. Seven compounds showed higher activity than prazosin, especially compound 8d having an IC(50) = 0.10 mM. Molecular modeling studies, including fitting of the synthesized compounds to a 3D-pharmacophore and their docking into optimized homology model as alpha(1)-AR antagonists showed high docking score and fit values. Most vasodilation activities of tested compounds are consistent with their molecular modeling results. (C) 2012 Elsevier Masson SAS. All rights reserved.
