Abstract
Hydralazine has led to the synthesis of phthalazinone derivatives which induce vasorelaxation. A new series of 2-(aminoalkyl)-4-benzyl-2H-phthalazin-1-one derivatives has been synthesized to study their vasorelaxant activity. At the highest-studied concentration, most of the new compounds relaxed the denuded aortic rings precontracted with phenylephrine by 72.9-85.7%. Compound 25 (C25) suppressed almost totally the contractile effects of phenylephrine, high KCl concentration, ionomycin and caffeine related to the activation of Ca2+ channels, whereas its inhibitory effect was reversed with high CaCl2 concentrations. Vasodilator effects of C25 appear to be due exclusively to the reversible blockage of different calcium channels. As broad range calcium channel blocker, C25 seems to be suitable as a pharmacological tool for calcium channel research.
References
Oct 2, 1990·European Journal of Pharmacology·H K LeeN Sperelakis
Nov 1, 1989·Drugs·D McTavish, E M Sorkin
Jan 12, 2002·British Journal of Pharmacology·Ian McFadzean, Alan Gibson
Sep 25, 2002·Physiological Reviews·Michael Fill, Julio A Copello
Mar 12, 2005·American Journal of Physiology. Cell Physiology·Paul H RatzAmy S Miner
Jun 29, 2005·Bioorganic & Medicinal Chemistry Letters·Alejandro ZamilpaArturo San Feliciano
Mar 4, 2006·Bioorganic & Medicinal Chemistry Letters·Esther del OlmoArturo San Feliciano
Apr 27, 2007·Journal of Anesthesia·Takashi Akata
Jul 11, 2008·Progress in Biophysics and Molecular Biology·Christelle GuibertJean-Pierre Savineau
May 11, 2010·Maturitas·A VirdisS Taddei
Aug 24, 2010·Molecular Interventions·James W Putney
Sep 6, 2011·European Heart Journal·Ulrich Förstermann, William C Sessa
Feb 7, 2013·Microcirculation : the Official Journal of the Microcirculatory Society, Inc·Gregory C Amberg, Manuel F Navedo
Jun 16, 2014·European Journal of Medicinal Chemistry·Javier MunínDolores Viña
Mar 22, 2015·The Canadian Journal of Cardiology·Daniel T Lackland, Michael A Weber
Mar 25, 2015·PloS One·Paul FransenDorien M Schrijvers
Apr 3, 2016·Pharmacological Reviews·F V BrozovichK G Morgan
Oct 26, 2016·JCI Insight·Qingsong LinKunfu Ouyang