19077-98-6Relevant articles and documents
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Marschall et al.
, p. 597 (1938)
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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.
Method for synthesizing salazosulfapyridine by utilizing 2-aminopyridine as raw material
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Paragraph 0043, (2016/10/10)
The invention discloses a method for synthesizing salazosulfapyridine by utilizing 2-aminopyridine as a raw material. The method comprises the steps: step 1, performing a sulfamation reaction on 2-aminopyridine and para-acetylaminobenzene sulfonyl chloride in an aqueous solution of potassium carbonate; step 2, firstly performing hydrolyzation in DMSO-water mixed solution of sodium hydroxide, and then performing hydrochloric acid acidification; step 3, performing a diazo-reaction in an aqueous solution dissolving hydrochloric acid and sodium nitrite; step 4, performing a coupling reaction on diazonium salt and salicylic acid in an aqueous solution of sodium hydroxide. According to the method for synthesizing salazosulfapyridine by utilizing the 2-aminopyridine as the raw material, the 2-aminopyridine is taken as a starting raw material, and then is sequentially subjected to the sulfamation reaction, the hydrolyzation, the acidification, the diazo-reaction and the coupling reaction to obtain the salazosulfapyridine. The diazo-reaction and the coupling reaction have high conversation rate and a few side reaction so as to improve the purity of products and ensure the efficiency; furthermore, the source of the 2-aminopyridine is easy, the production cost is reduced, and the industrial production cost is large.