title: Clinical potential of nitric oxide-independent soluble guanylate cyclase activators.
abstract: A major problem with using nitrates in the treatment of ischemic heart disease is that tolerance develops to their vasodilatory actions. YC-1 was used as the lead compound to synthesize further nitric oxide-independent soluble guanylate cyclase activators, including BAY-41-2272 and BAY-41-8543. A nitric oxide and heme-independent activator of soluble guanylate cyclase, BAY-58-2667, was subsequently discovered by high-throughput screening. Tolerance to the vasodilatory actions of BAY-41-8543 and BAY-58-2667 does not develop. Results from animal studies have suggested that these compounds may have potential in the treatment of ischemic heart disease, essential and pulmonary hypertension, congestive heart failure, glomerulonephritis and erectile dysfunction.
authors.affiliation: Division of Health Practice, Auckland University of Technology-Akoranga Campus, Auckland, New Zealand. s.doggrell@xtra.co.nz
authors.forename: Sheila A
authors.initials: SA
authors.lastname: Doggrell
mesh_terms: D000818:Animals; D001565:Benzoates / Q000627:therapeutic use; D020536:Enzyme Activators / Q000627:therapeutic use*; D005921:Glomerulonephritis / Q000188:drug therapy; D006162:Guanylate Cyclase / Q000187:drug effects* / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D009025:Morpholines / Q000627:therapeutic use; D017202:Myocardial Ischemia / Q000188:drug therapy; D009569:Nitric Oxide / Q000502:physiology*; D011743:Pyrimidines / Q000627:therapeutic use
chemical_list: C450679:BAY 41-8543; D001565:Benzoates; D020536:Enzyme Activators; D009025:Morpholines; D011743:Pyrimidines; D009569:Nitric Oxide; C480588:BAY 58-2667; D006162:Guanylate Cyclase