Identification of novel glycine sulfonamide antagonists for the EP1 receptor

Bioorganic and Medicinal Chemistry Letters

Volumn 17, Issue 6, 2007, Pages 1750-1754

  McKeown, Stephen C ^a   Hall, Adrian ^a   Blunt, Richard ^a   Brown, Susan H ^a   Chessell, Iain P ^a   Chowdhury, Anita ^a   Giblin, Gerard M P ^a   Healy, Mark P ^a   Johnson, Matthew R ^a   Lorthioir, Olivier ^a   Michel, Anton D ^a   Naylor, Alan ^a   Lewell, Xiao ^a   Roman, Shilina ^a   Watson, Stephen P ^a   Winchester, Wendy J ^a   Wilson, Richard J ^a  

^a GLAXOSMITHKLINE   (United Kingdom)

Author keywords

EP1 antagonist; Pain; Prostanoid; Pyrazole

Indexed keywords

GLYCINE SULFONAMIDE DERIVATIVE; PROSTAGLANDIN E RECEPTOR; PROSTAGLANDIN RECEPTOR BLOCKING AGENT; SULFONAMIDE; UNCLASSIFIED DRUG;

ARTICLE; DRUG POTENCY; DRUG SYNTHESIS; HIGH THROUGHPUT SCREENING; STRUCTURE ACTIVITY RELATION;

ANIMALS; CELL MEMBRANE; CHO CELLS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; CRICETINAE; CRICETULUS; CYTOCHROME P-450 ENZYME SYSTEM; DINOPROSTONE; DRUG EVALUATION, PRECLINICAL; GLYCINE AGENTS; HUMANS; INDICATORS AND REAGENTS; RECEPTORS, PROSTAGLANDIN E; RECEPTORS, PROSTAGLANDIN E, EP1 SUBTYPE; SULFONAMIDES;

EID: 33847119963     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2006.12.060     Document Type: Article

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14. 2. Calcium-sensitive dye (Fluo-3) was assessed using a Fluorimetric Image Plate Reader (FLIPR). Values are means of at least two experiments unless specified.
15. 6
16. 2 (3 nM final assay concentration) were incubated in a final volume of 100 μL for 30 min at 30 °C. The radioactivity retained was measured by liquid scintillation counting in a Packard TopCount scintillation counter. Values are means of at least four experiments.
17. 50 values in the absence and presence of antagonist were obtained. Dose ratios were calculated and then the log (dose ratio - 1) was plotted against Log (antagonist) concentration to produce the Schild graph from which the pA2 value and the slope were determined by linear regression.
18. Alkylating agents 11 and 12 can be prepared by coupling the appropriate amine in DMF with bromoacetic acid using DIC.