94749-73-2Relevant articles and documents
Novel Bivalent Ligands Based on the Sumanirole Pharmacophore Reveal Dopamine D2 Receptor (D2R) Biased Agonism
Bonifazi, Alessandro,Yano, Hideaki,Ellenberger, Michael P.,Muller, Ludovic,Kumar, Vivek,Zou, Mu-Fa,Cai, Ning Sheng,Guerrero, Adrian M.,Woods, Amina S.,Shi, Lei,Newman, Amy Hauck
, p. 2890 - 2907 (2017/04/21)
The development of bivalent ligands has attracted interest as a way to potentially improve the selectivity and/or affinity for a specific receptor subtype. The ability to bind two distinct receptor binding sites simultaneously can allow the selective activation of specific G-protein dependent or β-arrestin-mediated cascade pathways. Herein, we developed an extended SAR study using sumanirole (1) as the primary pharmacophore. We found that substitutions in the N-1- and/or N-5-positions, physiochemical properties of those substituents, and secondary aromatic pharmacophores can enhance agonist efficacy for the cAMP inhibition mediated by Gi/o-proteins, while reducing or suppressing potency and efficacy toward β-arrestin recruitment. Compound 19 was identified as a new lead for its selective D2 G-protein biased agonism with an EC50 in the subnanomolar range. Structure-activity correlations were observed between substitutions in positions N-1 and/or N-5 of 1 and the capacity of the new bivalent compounds to selectively activate G-proteins versus β-arrestin recruitment in D2R-BRET functional assays.
An efficient and practical synthesis of salmeterol
Lu, Yongping,Xu, Xinliang,Zhang, Xingxian
, p. 168 - 172 (2015/05/20)
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SUBSTITUTED ETHANOLAMINES
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Page/Page column 20, (2010/02/17)
The present invention relates to new substituted ethanolamine adrenergic receptor modulators, pharmaceutical compositions thereof, and methods of use thereof.