Discovery of IWP-051, a Novel Orally Bioavailable Soluble Guanylate Cyclase Stimulator with Sustained and Dose-Dependent Hemodynamic Effects
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KeywordsNitric Oxide Plasma Protein Binding Metabolic Stability Soluble Guanylate Cyclase Early Lead
Soluble guanylate cyclase (sGC) stimulators are small molecule agonists of sGC that are heme-dependent, nitric oxide (NO)-independent, and act in synergy with NO. Herein, we describe a novel class of pyrazole-pyrimidine sGC stimulators and their evolution from an early lead to IWP-051 by optimizing SAR for in vitro potency, pharmacokinetic parameters, and off-target activity.
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