Sumaiya Nahid, Fahad Imtiaz Rahman, Yu Du, Brittany D Spitznagel, Sandeep K Singh, Yashpal S Chhonker, Daryl J Murry, C David Weaver, Corey R Hopkins
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Further Structure-Activity Relationship of G Protein-Gated Inwardly Rectifying Potassium Channels 1/2 Activators: Synthesis and Biological Characterization of In Vitro Tool Compounds.
The work presented herein outlines the ongoing structure-activity relationship studies centered around a potent, efficacious, and selective activators of the G protein-gated inwardly rectifying potassium channels (GIRK)1/2 channel. Optimization studies centered around the pyrazole privileged scaffold, the N-1-position of the pyrazole, and the right-hand ether. The work confirms the necessity of the pyrazole, and a more potent GIRK1/2 activator is identified with ≈12-fold selectivity against GIRK1/4. The metabolite ID study is reported which shows the instability of the amide bond as the major site of metabolism (nonNADPH mediated). This work discovers another highly potent and selective GIRK1/2 activator for use as an in vitro tool compound.
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Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies.
ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs.
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