Author/Authors :
Andrew G. Cole، نويسنده , , Ilana L. Stroke، نويسنده , , Lan-Ying Qin، نويسنده , , Zahid Hussain، نويسنده , , Srilatha Simhadri، نويسنده , , Marc-Raleigh Brescia، نويسنده , , Frank S. Waksmunski، نويسنده , , Barbara Strohl، نويسنده , , John E. Tellew، نويسنده , , John P. Williams، نويسنده , , John Saunders، نويسنده , , Kenneth C. Appell، نويسنده , , Ian Henderson، نويسنده , , Maria L. Webb، نويسنده ,
Abstract :
The discovery and synthesis of a series of (dimethoxyphenoxy)alkylamino acetamides as orexin-2 receptor antagonists from a small-molecule combinatorial library using a high-throughput calcium mobilization functional assay (HEK293—human OX2-R cell line) is described. Active compounds show a good correlation between high-throughput single concentration screening data and measured IC50s. Specific examples exhibit IC50 values of not, vert, similar20 nM using human orexin A as the peptide agonist for the orexin-2 receptor.
Keywords :
combinatorial chemistry , Hypocretin , orexin , ECLiPSTM , GPCR
