| Literature DB >> 34365128 |
Kevin M Gayler1, Jeremy M Quintana1, Jordan Mattke1, Michael A Plunk1, Jessica H Kostyo1, Johann W Karunananthan1, Harold Nguyen1, Mina Shuda1, Liam D Ferreira1, Hannah Baker1, Alexandra L Stinchcomb1, Iraida Sharina2, Robert R Kane3, Emil Martin4.
Abstract
Previous studies demonstrated that anti-hyperlipidemic drug gemfibrozil acts as NO- and heme-independent activator of NO receptor soluble guanylyl cyclase. A series of new gemfibrozil derivatives were synthesized and evaluated for sGC activation. The structure-activity relationship study identified the positions in gemfibrozil's scaffold that are detrimental for sGC activation and those that are amendable for optimizing modifications. Compared with gemfibrozil, compounds 7c and 15b were more potent activators of cGMP-forming activity of purified sGC and exhibited enhanced relaxation of preconstricted mouse thoracic aorta rings. These studies established the overall framework needed for futher improvement of sGC activators based on gemfibrozil scaffold.Entities:
Keywords: Biochemistry; Gemfibrozil; Medicinal chemistry; Soluble guanylyl cyclase
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Year: 2021 PMID： 34365128 PMCID： PMC8511081 DOI： 10.1016/j.ejmech.2021.113729
Source DB: PubMed Journal: Eur J Med Chem ISSN： 0223-5234 Impact factor: 6.514