Potent oxadiazole CGRP receptor antagonists for the potential treatment of migraine

Bioorganic and Medicinal Chemistry Letters

Volumn 20, Issue 4, 2010, Pages 1368-1372

  Nichols, Paula L ^a   Brand, Jonathan ^a   Briggs, Michael ^a   D'Angeli, Mathilde ^a   Farge, Jennifer ^a   Garland, Stephen L ^a   Goldsmith, Paul ^a   Hutchings, Rio ^a   Kilford, Ian ^a   Li, Ho Y ^a   MacPherson, David ^a   Nimmo, Fiona ^a   Sanderson, Francis Dominic ^a   Sehmi, Sanjeet ^a   Shuker, Nicola ^a   Skidmore, John ^a   Stott, Michael ^a   Sweeting, Jennifer ^a   Tajuddin, Hasmi ^a   Takle, Andrew K ^a   Trani, Giancarlo ^a   Wall, Ian D ^a   Ward, Robert ^a   Wilson, David M ^a   Witty, David ^a   more..

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

CGRP; CGRP receptor antagonists; Migraine; Oxadiazoles

Indexed keywords

ANTIMIGRAINE AGENT; CALCITONIN GENE RELATED PEPTIDE RECEPTOR ANTAGONIST; METHYLCELLULOSE; OXADIAZOLE DERIVATIVE;

ANIMAL EXPERIMENT; AREA UNDER THE CURVE; ARTICLE; CONTROLLED STUDY; DRUG ABSORPTION; DRUG BIOAVAILABILITY; DRUG FORMULATION; DRUG IDENTIFICATION; DRUG PENETRATION; DRUG POTENCY; DRUG SOLUBILITY; DRUG SYNTHESIS; MAXIMUM PLASMA CONCENTRATION; NONHUMAN; PHARMACOPHORE; PROCESS OPTIMIZATION; RAT; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; ANIMALS; DRUG DESIGN; MIGRAINE DISORDERS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; OXADIAZOLES; RATS; RECEPTORS, CALCITONIN GENE-RELATED PEPTIDE;

EID: 75449111000     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2010.01.012     Document Type: Article

References (18)

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13. i) for antagonism of CGRP-stimulated increases in intracellular cAMP was determined in HEK 293 cells expressing the human recombinant receptor. Compounds which had encouraging potency in the absence of HSA were then screened in the presence of HSA to give a better prediction of the in vivo potency. For details of this assay, see: Nichols, P. L.; Skidmore, J.; Ward, R. W.; Wilson, D. M. WO2009/000819 A1.
14. Scheme 1 details the most common route used to synthesise compounds of the type 9a-t. Alternative syntheses can be found in Nichols, P. L.; Skidmore, J.; Ward, R. W.; Wilson, D. M. WO2009/000819 A1.
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