Wy‐46,300 and Wy‐46,531: Vascular Smooth Muscle Relaxant/Antihypertensive Agents with Combined Ca2+ Antagonist/Myosin Phosphorylation Inhibitory Mechanisms

@article{Silver1986Wy46300AW,
  title={Wy‐46,300 and Wy‐46,531: Vascular Smooth Muscle Relaxant/Antihypertensive Agents with Combined Ca2+ Antagonist/Myosin Phosphorylation Inhibitory Mechanisms},
  author={Paul J. Silver and Theodore S. Sulkowski and Rodney W. Lappe and Robert L. Wendt},
  journal={Journal of Cardiovascular Pharmacology},
  year={1986},
  volume={8},
  pages={1168–1175}
}
1,4,5,6,7,8-hexahydro-2-methyl-5-oxo-4-(pentafluorophenyl) −1,7 - naphthyridine - 3 - carboxylic acid methyl ester hydrochlorides with either a 3-phenoxy-2-hydroxypropyl (Wy-46,300) or 2-hydroxy-4-phenylbutyl (Wy-46,531) substituent at the 7 position are structurally novel vascular relaxant compounds which lower blood pressure by ∼35 mm Hg at 25 mg/kg p.o. in spontaneously hypertensive rats (SHR) or perinephritic hypertensive beagles. In contrast to standard Ca2+ blockers, both agents also… Expand
3 Citations
Calcium-regulated protein kinases and low Km cGMP phosphodiesterases: targets for novel antihypertensive therapy.
TLDR
This review focuses on three intracellular enzyme systems: myosin light chain kinase (MLCK) and protein kinase C (PKC), which are Ca2+-regulated protein kinases implicated in the control of smooth muscle tone, and the cGMP phosphodiesterases (PDEs), which regulate the levels of cG MP in smooth muscle. Expand
Calcium channel antagonists part V: Second-generation agents
  • L. Opie
  • Medicine
  • Cardiovascular Drugs and Therapy
  • 2004
TLDR
From all these agents will be selected those that are longer-acting and provide higher vascular selectivity, including diphenylalkylamines, bepridil is of special interest. Expand
Second-Generation Agents
TLDR
From all these agents will be selected those that are longer-acting and provide higher vascular selectivity, including diphenylalkylamines, diltiazem, and verapamil, the latter of which is of special interest. Expand