The design and synthesis of YC-1 analogues as probes for soluble guanylate cyclase.
Soluble guanylate cyclase (sGC) is highly activated in the presence of both YC-1 (1-benzyl-3-(5'-hydroxymethyl-2'-furyl)-indazole) and CO. In this report, the design, synthesis, and activity (i.e., sGC activation) of photolabile analogues of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1) are presented. Initial results with 6-azido-3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole led to the synthesis of a tritium-labeled analogue. When photoactivated, this analogue labeled the alpha-subunit of sGC.
Hering
Kirk W
KW
Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USA.
Artz
Jennifer D
JD
Pearson
William H
WH
Marletta
Michael A
MA
D015195:Drug Design; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000737:chemistry / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000737:chemistry* / Q000378:metabolism; D007191:Indazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D015394:Molecular Structure; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology; D012995:Solubility; D014316:Tritium / Q000737:chemistry
D020536:Enzyme Activators; D007191:Indazoles; D010975:Platelet Aggregation Inhibitors; D014316:Tritium; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole; D006162:Guanylate Cyclase