1. Identification of 2-oxo-N-(phenylmethyl)-4-imidazolidinecarboxamide antagonists of the P2X(7) receptor.
- Author
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Abberley L, Bebius A, Beswick PJ, Billinton A, Collis KL, Dean DK, Fonfria E, Gleave RJ, Medhurst SJ, Michel AD, Moses AP, Patel S, Roman SA, Scoccitti T, Smith B, Steadman JG, and Walter DS
- Subjects
- Administration, Oral, Animals, Biological Availability, Half-Life, Haplorhini, Imidazolines administration & dosage, Imidazolines chemistry, Imidazolines pharmacokinetics, Purinergic Antagonists administration & dosage, Purinergic Antagonists chemistry, Purinergic Antagonists pharmacokinetics, Rats, Imidazolines pharmacology, Purinergic Antagonists pharmacology, Receptors, Purinergic P2X7 drug effects
- Abstract
A backup molecule to compound 2 was sought by targeting the most likely metabolically vulnerable site in this molecule. Compound 18 was subsequently identified as a potent P2X(7) antagonist with very low in vivo clearance and high oral bioavailability in all species examined. Some evidence to support the role of P2X(7) in the etiology of pain is also presented., (Copyright © 2010 Elsevier Ltd. All rights reserved.)
- Published
- 2010
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