889676-37-3Relevant articles and documents
Structure-Guided Modification of Heterocyclic Antagonists of the P2Y14 Receptor
Yu, Jinha,Ciancetta, Antonella,Dudas, Steven,Duca, Sierra,Lottermoser, Justine,Jacobson, Kenneth A.
supporting information, p. 4860 - 4882 (2018/06/20)
The P2Y14 receptor (P2Y14R) mediates inflammatory activity by activating neutrophil motility, but few classes of antagonists are known. We have explored the structure-activity relationship of a 3-(4-phenyl-1H-1,2,3-triazol-1-yl)-5-(aryl)benzoic acid antagonist scaffold, assisted by docking and molecular dynamics (MD) simulation at a P2Y14R homology model. A computational pipeline using the High Throughput MD Python environment guided the analogue design. Selection of candidates was based upon ligand-protein shape and complementarity and the persistence of ligand-protein interactions over time. Predictions of a favorable substitution of a 5-phenyl group with thiophene and an insertion of a three-methylene spacer between the 5-aromatic and alkyl amino moieties were largely consistent with empirical results. The substitution of a key carboxylate group on the core phenyl ring with tetrazole or truncation of the 5-aryl group reduced affinity. The most potent antagonists, using a fluorescent assay, were a primary 3-aminopropyl congener 20 (MRS4458) and phenyl p-carboxamide 30 (MRS4478).
A method of preparing amide compounds
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Paragraph 0033-0036, (2017/02/09)
The invention belongs to the field of organic compound preparation, and particularly relates to a method for preparing an amide compound. Specifically, cyano compounds are subjected to selective hydrolysis with a mixed solvent of a protic solvent and a non protonic solvent as a reaction medium under the conditions of heating and alkaline catalysis in the air atmosphere, so as to efficiently produce corresponding amide compounds; at the same time, carbon-carbon coupling reaction can be further utilized to react a compound containing cyano group and halogen group with a boronic acid compound, so as to prepare coupled amide compound through a one-step preparation method. The method avoids the usage of traditional toxic and harmful oxidants such as hydrogen peroxide, and is simple, efficient and green synthesis method for preparing the amide compound.
