- 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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- 2-substituted homotaurine derivative
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The invention provides preparation and applications of a 2-substituted homotaurine derivative or a stereoisomer or a salt thereof, wherein the 2-substituted homotaurine derivative is represented by aformula I. According to the invention, the pharmacodynamic test results show that the 2-substituted homotaurine derivative is excellent in alcohol inhibition effect and has ideal application prospectof alcohol inhibition drugs.
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Paragraph 0084-0086
(2020/01/25)
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- HETEROCYCLIC COMPOUNDS AND USE THEREOF AS MODULATORS OF TYPE III RECEPTOR TYROSINE KINASES
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Provided herein are heterocyclic compounds for treatment of CSF1R, FLT3, KIT, and/or PDGFRβ kinase mediated diseases. Also provided are pharmaceutical compositions comprising the compounds and methods of using the compounds and compositions.
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Paragraph 0570
(2016/08/03)
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- Synthesis of oxazolidin-2-ones and imidazolidin-2-ones directly from 1,3-diols or 3-amino alcohols using iodobenzene dichloride and sodium azide
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A general and efficient method for the synthesis of oxazolidin-2-ones and imidazolidin-2-ones directly from 1,3-diols and 3-amino alcohols has been developed using the same reagent combination of iodobenzene dichloride (PhICl2) and sodium azide (NaN3).
- He, Tian,Gao, Wen-Chao,Wang, Wei-Kun,Zhang, Chi
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supporting information
p. 1113 - 1118
(2014/04/03)
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- Synthesis and biological evaluation of cryptophycin analogs with substitution at C-6 (fragment C region)
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Analogs of the antitumor agents cryptophycins 1 and 8 with dialkyl substitution at C-6 (fragment C) were synthesized and evaluated for in vitro cytotoxicity against human leukemia cells (CCRF-CEM). The activity of these analogs decreased as the size of the substituents at C-6 increased. The C-6 spirocylopropyl compound (2g) was highly potent in vitro and showed excellent antitumor activity in animal models.
- Varie, David L.,Shih, Chuan,Hay, David A,Andis, Sherri L.,Corbett, Tom H.,Gossett, Lynn S.,Janisse, Samantha K.,Martinelli, Michael J.,Moher, Eric D.,Schultz, Richard M.,Toth, John E.
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p. 369 - 374
(2007/10/03)
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