301672-76-4Relevant academic research and scientific papers
Design, Synthesis, and in vitro Evaluation of P2X7 Antagonists
Durner, Anna,Koufaki, Maria,Kritsi, Eftichia,Nicke, Annette,Papakostas, Alexios,T. Pournara, Dimitra,Zoumpoulakis, Panagiotis
, p. 2530 - 2543 (2020/10/19)
The P2X7 receptor is a promising target for the treatment of various diseases due to its significant role in inflammation and immune cell signaling. This work describes the design, synthesis, and in vitro evaluation of a series of novel derivatives bearing diverse scaffolds as potent P2X7 antagonists. Our approach was based on structural modifications of reported (adamantan-1-yl)methylbenzamides able to inhibit the receptor activation. The adamantane moieties and the amide bond were replaced, and the replacements were evaluated by a ligand-based pharmacophore model. The antagonistic potency of the synthesized analogues was assessed by two-electrode voltage clamp experiments, using Xenopus laevis oocytes that express the human P2X7 receptor. SAR studies suggested that the replacement of the adamantane ring by an aryl-cyclohexyl moiety afforded the most potent antagonists against the activation of the P2X7 cation channel, with analogue 2-chloro-N-[1-(3-(nitrooxymethyl)phenyl)cyclohexyl)methyl]benzamide (56) exhibiting the best potency with an IC50 value of 0.39 μΜ.
Discovery of potent and selective adamantane-based small-molecule P2X 7 receptor antagonists/interleukin-1β inhibitors
Furber, Mark,Alcaraz, Lilian,Bent, Janice E.,Beyerbach, Armin,Bowers, Keith,Braddock, Martin,Caffrey, Moya V.,Cladingboel, David,Collington, John,Donald, David K.,Fagura, Malbinder,Ince, Frank,Kinchin, Elizabeth C.,Laurent, Celine,Lawson, Mandy,Luker, Timothy J.,Mortimore, Michael M. P.,Pimm, Austen D.,Riley, Robert J.,Roberts, Nicola,Robertson, Mark,Theaker, Jill,Thorne, Philip V.,Weaver, Richard,Webborn, Peter,Willis, Paul
, p. 5882 - 5885 (2008/03/30)
A novel series of antagonists of the human P2X7 receptor is described. Modification of substituents enabled identification of compounds selective for the rat P2X7 receptor and provides useful pharmacological tools for evaluation of t
Adamantane derivatives
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, (2008/06/13)
The invention provides compounds of general formula in which m, A, R1and Ar have the meanings defined in the specification; a process for their preparation; pharmaceutical compositions containing them; a process for preparing the pharmaceutical compositions; and their use in therapy.
