41862-11-7Relevant articles and documents
Structure-Affinity Relationships and Structure-Kinetics Relationships of Pyrido[2,1-f]purine-2,4-dione Derivatives as Human Adenosine A3 Receptor Antagonists
Xia, Lizi,Burger, Wessel A. C.,Van Veldhoven, Jacobus P. D.,Kuiper, Boaz J.,Van Duijl, Tirsa T.,Lenselink, Eelke B.,Paasman, Ellen,Heitman, Laura H.,Ijzerman, Adriaan P.
, p. 7555 - 7568 (2017)
We expanded on a series of pyrido[2,1-f]purine-2,4-dione derivatives as human adenosine A3 receptor (hA3R) antagonists to determine their kinetic profiles and affinities. Many compounds showed high affinities and a diverse range of k
Development of Covalent Ligands for G Protein-Coupled Receptors: A Case for the Human Adenosine A3 Receptor
Yang, Xue,Van Veldhoven, Jacobus P. D.,Offringa, Jelle,Kuiper, Boaz J.,Lenselink, Eelke B.,Heitman, Laura H.,Van Der Es, Daan,Ijzerman, Adriaan P.
, p. 3539 - 3552 (2019/04/16)
The development of covalent ligands for G protein-coupled receptors (GPCRs) is not a trivial process. Here, we report a streamlined workflow thereto from synthesis to validation, exemplified by the discovery of a covalent antagonist for the human adenosine A3 receptor (hA3AR). Based on the 1H,3H-pyrido[2,1-f]purine-2,4-dione scaffold, a series of ligands bearing a fluorosulfonyl warhead and a varying linker was synthesized. This series was subjected to an affinity screen, revealing compound 17b as the most potent antagonist. In addition, a nonreactive methylsulfonyl derivative 19 was developed as a reversible control compound. A series of assays, comprising time-dependent affinity determination, washout experiments, and [35S]GTPγS binding assays, then validated 17b as the covalent antagonist. A combined in silico hA3AR-homology model and site-directed mutagenesis study was performed to demonstrate that amino acid residue Y2657.36 was the unique anchor point of the covalent interaction. This workflow might be applied to other GPCRs to guide the discovery of covalent ligands.
Synthesis and evaluation of antitumour activities of novel fused tri-And tetracyclic uracil derivatives
Elkalyoubi, Samar,Fayed, Eman
, p. 771 - 777 (2017/01/03)
Simple one-pot syntheses of indenopyrrolopyrimidines and indolopyrrolopyrimidines were achieved via the cyclocondensation of 6-Aminouracils and, respectively, ninhydrin and isatin in the presence of catalytic amounts of glacial acetic acid. Similarly, 5,6-diaminouracil derivatives were used as starting materials for the synthesis of indenopteridines and indolopteridines via their reaction with ninhydrin and isatin, respectively. The synthesised compounds were evaluated for antitumour activity against a human hepatocellular carcinoma cell line (HepG2), some showing antitumour activity comparable with 5-fluorouracil and imatinib.
