Εξειδίκευση τύπου :	Άρθρο σε επιστημονικό περιοδικό
Τίτλος:	Design, synthesis, and in vitro evaluation of P2X7 antagonists
Δημιουργός/Συγγραφέας:	Pournara, Dimitra T. Durner, Anna Kritsi, Eftichia Papakostas, Alexios [EL] Ζουμπουλάκης, Παναγιώτης[EN] Zoumpoulakis, Panagiotis Nicke, Annette [EL] Κουφάκη, Μαρία[EN] Koufaki, Maria
Εκδότης:	Wiley
Ημερομηνία:	2020-12-15
Γλώσσα:	Αγγλικά
ISSN:	1860-7179 1860-7187
DOI:	10.1002/cmdc.202000303
Άλλο:	32964578
Περίληψη:	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 μM.
Τίτλος πηγής δημοσίευσης:	ChemMedChem
Τόμος/Κεφάλαιο:	15
Τεύχος:	24
Σελίδες:	2530-2543
Θεματική Κατηγορία:	[EL] Χημική Βιολογία[EN] Chemical Biology [EL] Χημεία (Γενικά)[EN] Chemistry (General) [EL] Φαρμακευτική χημεία[EN] Pharmaceutical chemistry
Λέξεις-Κλειδιά:	P2X7 antagonists Adamant-1-yl Aryl-cyclohexyl Structure-Activity Relationship Two-electrode voltage clamp Adamantane Animals Benzamides Cyclohexanes Drug Design Humans Molecular Structure Purinergic P2X Receptor Antagonists Receptors, Purinergic P2X7 Structure-Activity Relationship Xenopus laevis
Κάτοχος πνευματικών δικαιωμάτων:	Copyright © 2020 John Wiley & Sons, Inc. All rights reserved
Ηλεκτρονική διεύθυνση στον εκδότη (link):	https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/cmdc.202000303
Ηλεκτρονική διεύθυνση περιοδικού (link) :	https://chemistry-europe.onlinelibrary.wiley.com/journal/18607187
Εμφανίζεται στις συλλογές:	Ινστιτούτο Χημικής Βιολογίας - Επιστημονικό έργο