التفاصيل البيبلوغرافية
| العنوان: |
Gemfibrozil derivatives as activators of soluble guanylyl cyclase – A structure-activity study. |
| المؤلفون: |
Gayler, Kevin M.1 (AUTHOR), Quintana, Jeremy M.1 (AUTHOR), Mattke, Jordan1 (AUTHOR), Plunk, Michael A.1 (AUTHOR), Kostyo, Jessica H.1 (AUTHOR), Karunananthan, Johann W.1 (AUTHOR), Nguyen, Harold1 (AUTHOR), Shuda, Mina1 (AUTHOR), Ferreira, Liam D.1 (AUTHOR), Baker, Hannah1 (AUTHOR), Stinchcomb, Alexandra L.1 (AUTHOR), Sharina, Iraida2 (AUTHOR), Kane, Robert R.1 (AUTHOR) Bob_kane@Baylor.edu, Martin, Emil1,2 (AUTHOR) emil.martin@uth.tmc.edu |
| المصدر: |
European Journal of Medicinal Chemistry. Nov2021, Vol. 224, pN.PAG-N.PAG. 1p. |
| مصطلحات موضوعية: |
*GUANYLATE cyclase, *THORACIC aorta, *STRUCTURE-activity relationships, *PHARMACEUTICAL chemistry |
| مستخلص: |
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. [Display omitted] • New gemfibrozil-based activators of soluble guanylyl cyclase (sGC) were synthesized and tested. • Compounds 7c and 15b have better half maximal effective concentration than gemfibrozil in sGC assay. • Compounds 7c and 15b were more effective vasorelaxants than gemfibrozil. [ABSTRACT FROM AUTHOR] |
| قاعدة البيانات: |
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