Potent oxadiazole CGRP receptor antagonists for the potential treatment of migraine.

Autor: Nichols PL; Department of Medicinal Chemistry, Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. paula.l.nichols@gsk.com, Brand J, Briggs M, D'Angeli M, Farge J, Garland SL, Goldsmith P, Hutchings R, Kilford I, Li HY, MacPherson D, Nimmo F, Sanderson FD, Sehmi S, Shuker N, Skidmore J, Stott M, Sweeting J, Tajuddin H, Takle AK, Trani G, Wall ID, Ward R, Wilson DM, Witty D
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2010 Feb 15; Vol. 20 (4), pp. 1368-72. Date of Electronic Publication: 2010 Jan 11.
DOI: 10.1016/j.bmcl.2010.01.012
Abstrakt: A pharmacophore model was built, based on known CGRP receptor antagonists, and this was used to aid the identification of novel leads. Analogues were designed, modelled and synthesised which incorporated alternative 'LHS' fragments linked via either an amide or urea to a privileged 'RHS' fragment commonly found in CGRP receptor antagonists. As a result a novel series of oxadiazole CGRP receptor antagonists has been identified and the subsequent optimisation to enhance both potency and bioavailability is presented.
(Copyright 2010 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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