Synthesis and evaluation of a phosphonate analogue of the soluble guanylate cyclase activator YC-1

Nathaniel I Martin; Emily R Derbyshire; Michael A Marletta

doi:10.1016/j.bmcl.2007.06.039

Synthesis and evaluation of a phosphonate analogue of the soluble guanylate cyclase activator YC-1

Bioorg Med Chem Lett. 2007 Sep 1;17(17):4938-41. doi: 10.1016/j.bmcl.2007.06.039. Epub 2007 Jun 14.

Authors

Nathaniel I Martin¹, Emily R Derbyshire, Michael A Marletta

Affiliation

¹ Department of Chemistry, University of California, Berkeley, CA 94720, USA.

PMID: 17587571
DOI: 10.1016/j.bmcl.2007.06.039

Abstract

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.

MeSH terms

Alcohols / chemistry
Chemistry, Pharmaceutical / methods*
Drug Design
Electrons
Enzyme Activation
Enzyme Activators / chemical synthesis*
Enzyme Activators / chemistry
Guanosine Triphosphate / chemistry
Guanylate Cyclase / metabolism
Heme / chemistry
Indazoles / chemical synthesis
Indazoles / chemistry*
Kinetics
Models, Chemical
Nitric Oxide / chemistry
Organophosphonates / chemistry*
Phosphorylation
Receptors, Cytoplasmic and Nuclear / metabolism
Soluble Guanylyl Cyclase
Temperature

Substances

Alcohols
Enzyme Activators
Indazoles
Organophosphonates
Receptors, Cytoplasmic and Nuclear
3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
Nitric Oxide
Heme
Guanosine Triphosphate
Guanylate Cyclase
Soluble Guanylyl Cyclase