- Design, Synthesis, and in vitro Evaluation of P2X7 Antagonists
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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.
- Durner, Anna,Koufaki, Maria,Kritsi, Eftichia,Nicke, Annette,Papakostas, Alexios,T. Pournara, Dimitra,Zoumpoulakis, Panagiotis
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supporting information
p. 2530 - 2543
(2020/10/19)
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- Pharmacochemistry of the furoxan ring: Recent developments
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In the present work recent results obtained in the pharmacochemistry of the furoxan system are reported. In particular, after a brief description of the salient points of the furoxan chemistry, the synthesis and the properties of a series of Nifedipine and Prazosin analogues, containing this heterocyclic system, are described. Since we observed that a few furoxan derivatives are able to elicit both a dose-dependent rise in platelet cGMP levels and to promote a dose-dependent inhibition of AA-induced [Ca++] rise, and that many substituted furoxans show potent vasodilating and antiaggregatory activity, the possibility of using the furoxan system as a lead in the design of new vasodilators is also discussed.
- Calvino,Di Stilo,Fruttero,Gasco,Sorba,Gasco
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p. 321 - 334
(2007/10/02)
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- Unsymmetrically Substituted Furoxans, XIII. Phenylfuroxancarbaldehydes and Related Compounds
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The synthesis and structure of two isomeric phenylfuroxancarbaldehydes 7a and 7b, of the phenylfurazancarbaldehyde 6 and of the corresponding alcohols 3a, 3b and 5 are reported.Thermal equilibration of the furoxan derivatives and their oxidation to the co
- Gasco, Andrea Marcello,Fruttero, Roberta,Sorba, Giovanni,Gasco, Alberto
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p. 1211 - 1213
(2007/10/02)
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