- 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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p. 2530 - 2543
(2020/10/19)
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- Mechanistic Studies into the Oxidative Addition of Co(I) Complexes: Combining Electroanalytical Techniques with Parameterization
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The oxidative addition of organic electrophiles into electrochemically generated Co(I) complexes has been widely utilized as a strategy to produce carbon-centered radicals when cobalt is ligated by a polydentate ligand. Changing to a bidentate ligand prov
- Sandford, Christopher,Fries, Lydia R.,Ball, Tyler E.,Minteer, Shelley D.,Sigman, Matthew S.
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p. 18877 - 18889
(2019/11/28)
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- 2,6,7,8 SUBSTITUTED PURINES AS HDM2 INHIBITORS
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The present invention provides 2,6,7,8 Substituted Purines as described herein or a pharmaceutically acceptable salt thereof. The representative compounds are useful as inhibitors of the HDM2 protein. Also disclosed are pharmaceutical compositions compris
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