19838-02-9Relevant academic research and scientific papers
Structure-activity relationships of agonists for the orphan G protein-coupled receptor GPR27
Blavier, Jeremy,Charles, Ma?lle,Hanson, Julien,Kronenberger, Thales,Laschet, Céline,Müller, Christa E.,Pillaiyar, Thanigaimalai,Rosato, Francesca,Wozniak, Monika
, (2021/08/27)
GPR27 belongs, with GPR85 and GPR173, to a small subfamily of three receptors called “Super-Conserved Receptors Expressed in the Brain” (SREB). It has been postulated to participate in key physiological processes such as neuronal plasticity, energy metabolism, and pancreatic β-cell insulin secretion and regulation. Recently, we reported the first selective GPR27 agonist, 2,4-dichloro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (I, pEC50 6.34, Emax 100%). Here, we describe the synthesis and structure-activity relationships of a series of new derivatives and analogs of I. All products were evaluated for their ability to activate GPR27 in an arrestin recruitment assay. As a result, agonists were identified with a broad range of efficacies including partial and full agonists, showing higher efficacies than the lead compound I. The most potent agonist was 4-chloro-2,5-difluoro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7y, pEC50 6.85, Emax 37%), and the agonists with higher efficacies were 4-chloro-2-methyl-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7p, pEC50 6.04, Emax 123%), and 2-bromo-4-chloro-N-(4-(N-phenylsulfamoyl)phenyl)benzamide (7r, pEC50 5.99, Emax 123%). Docking studies predicted the putative binding site and interactions of agonist 7p with GPR27. Selected potent agonists were found to be soluble and devoid of cellular toxicity within the range of their pharmacological activity. Therefore, they represent important new tools to further characterize the (patho)physiological roles of GPR27.
Nitrogen-containing polyhydroxylated aromatics as HIV-1 integrase inhibitors: Synthesis, structure-activity relationship analysis, and biological activity
Yu, Shenghui,Zhang, Linna,Yan, Shifeng,Wang, Peng,Sanchez, Tino,Christ, Frauke,Debyser, Zeger,Neamati, Nouri,Zhao, Guisen
, p. 628 - 640 (2012/10/29)
Four series of forty-five nitrogen-containing polyhydroxylated aromatics based on caffeic acid phenethyl ester were designed and synthesized as HIV-1 integrase (IN) inhibitors. Most of these compounds inhibited IN catalytic activities in low micromolar range. Among these new analogues, compounds 9e and 9f were the most potent IN inhibitors with IC50 value of 0.7 μM against strand transfer reaction. Their key structure-activity relationships were also discussed.
Design and synthesis of novel nitrogen-containing polyhydroxylated aromatics as HIV-1 integrase inhibitors from caffeic acid phenethyl ester
Wang, Peng,Liu, Chuan,Sanches, Tino,Zhong, Yuan,Liu, Bo,Xiong, Junlong,Neamati, Nouri,Zhao, Guisen
supporting information; experimental part, p. 4574 - 4578 (2010/04/24)
A series of nitrogen-containing polyhydroxylated aromatics from caffeic acid phenethyl ester were designed and synthesized as HIV-1 integrase inhibitors. Most of these compounds exhibited potent inhibitory activities at micromolar concentrations against HIV-1 integrase in the 3′-end processing and the strand transfer. Their key structure-activity relationship was also discussed.
