Synthesis and evaluation of a phosphonate analogue of the soluble guanylate cyclase activator YC-1.
Soluble guanylate cyclase (sGC) is activated by the known benzylindazole derivative YC-1 [1-benzyl-3-(5'-hydroxymethyl-2'-furyl)-indazole]. YC-1 also acts synergistically with CO, activating sGC to a level comparable to that achieved upon binding of nitric oxide, the endogenous activator of sGC. We here describe the synthesis of a YC-1 phosphonate analogue with improved aqueous solubility as well as its effects on sGC.
Martin
Nathaniel I
NI
Department of Chemistry, University of California, Berkeley, CA 94720, USA.
Derbyshire
Emily R
ER
Marletta
Michael A
MA
D000438:Alcohols / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004583:Electrons; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000138:chemical synthesis* / Q000737:chemistry; D006160:Guanosine Triphosphate / Q000737:chemistry; D006162:Guanylate Cyclase / Q000378:metabolism; D006418:Heme / Q000737:chemistry; D007191:Indazoles / Q000138:chemical synthesis / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D009569:Nitric Oxide / Q000737:chemistry; D063065:Organophosphonates / Q000737:chemistry*; D010766:Phosphorylation; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase; D013696:Temperature
D000438:Alcohols; D020536:Enzyme Activators; D007191:Indazoles; D063065:Organophosphonates; D018160:Receptors, Cytoplasmic and Nuclear; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D009569:Nitric Oxide; D006418:Heme; D006160:Guanosine Triphosphate; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase