Synthesis and biological activity of a series of tetrasubstituted-imidazoles as P2X(7) antagonists

Bioorganic & Medicinal Chemistry Letters
Robert J GleaveSac-Pham Tang

Abstract

A series of analogues of the pyrazole lead 1 were synthesized in which the heterocyclic core was replaced with an imidazole. A number of potent antagonists were identified and structure-activity relationships (SAR) were investigated both with respect to activity at the P2X(7) receptor and in vitro metabolic stability. Compound 10 was identified as a potent P2X(7) antagonist with reduced in vitro metabolism and high solubility.

References

Nov 19, 1997·Neuropharmacology·G ColloG Buell
Sep 25, 2001·Xenobiotica; the Fate of Foreign Compounds in Biological Systems·S E Clarke, P Jeffrey
Apr 12, 2008·Purinergic Signalling·Jane P HughesIain P Chessell
Apr 16, 2008·Expert Opinion on Therapeutic Targets·Romeo RomagnoliStefania Gessi

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Citations

May 2, 2012·Purinergic Signalling·Karina Kaczmarek-HájekAnnette Nicke
Dec 4, 2012·Indian Journal of Pharmaceutical Sciences·M S Y KhanM Rashid
Sep 17, 2014·Trends in Pharmacological Sciences·Beáta Sperlágh, Peter Illes
Oct 16, 2015·Journal of Medicinal Chemistry·Francisco Lopez-TapiaAndré Alker
Jun 24, 2015·ACS Medicinal Chemistry Letters·Brad M SavallMichael A Letavic

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