259540-82-4Relevant academic research and scientific papers
Structure activity relationship of 3-nitro-2-(trifluoromethyl)-2H-chromene derivatives as P2Y6 receptor antagonists
Jung, Young-Hwan,Jain, Shanu,Gopinatth, Varun,Phung, Ngan B.,Gao, Zhan-Guo,Jacobson, Kenneth A.
supporting information, (2021/04/23)
Various 6-alkynyl analogues of a known 3-nitro-2-(trifluoromethyl)-2H-chromene antagonist 3 of the Gq-coupled P2Y6 receptor (P2Y6R) were synthesized using a Sonogashira reaction to replace a 6-iodo group. The analogues were tested in a functional assay consisting of inhibition of calcium mobilization in P2Y6R-expressing astrocytoma cells elicited by native P2Y6R agonist UDP. 6-Ethynyl and 6-cyano groups were installed, and the alkynes were extended through both alkyl and aryl spacers. The most potent antagonists, with IC50 of ~1 μM, were found to be trialkylsilyl-ethynyl 7 and 8 (3–5 fold greater affinity than reference 3), t-butyl prop-2-yn-1-ylcarbamate 14 and p-carboxyphenyl-ethynyl 16 derivatives, and 3 and 8 displayed surmountable antagonism of UDP-induced production of inositol phosphates. Other chain-extended terminal carboxylate derivatives were less potent than the corresponding methyl ester derivatives. Thus, the 6 position in this chromene series is suitable for derivatization with flexibility of substitution, even with sterically extended chains, without losing P2Y6R affinity. However, a 3-carboxylic acid or 3-ester substitution did not serve as a nitro bioisostere, as the affinity was eliminated. These compounds provide additional ligand tools for the underexplored P2Y6R, which is a target for inflammatory, neurodegenerative and metabolic diseases.
N-(p-Ethynylbenzoyl) derivatives of amino acid and dipeptide methyl esters - Synthesis and structural study
Ei?mann, Frank,Weber, Edwin
experimental part, p. 121 - 128 (2012/01/04)
A series of N-(p-ethynylbenzoyl) derivatives (1-4) of the amino acids glycine and l-alanine as well as the dipeptides glycylglycine and l-alanylglycine has been synthesized via a two-step reaction sequence including the reaction of an appropriate N-(p-bro
