Title of article :
Discovery and optimization of (R)-prolinol-derived agonists of the Growth Hormone Secretagogue receptor (GHSR)
Author/Authors :
Weixu Zhai، نويسنده , , Neil Flynn، نويسنده , , Daniel A. Longhi، نويسنده , , Joseph A. Tino، نويسنده , , Brian J. Murphy، نويسنده , , Dorothy Slusarchyk، نويسنده , , David A. Gordon، نويسنده , , Anna Pendri، نويسنده , , Shuhao Shi، نويسنده , , Robert Stoffel، نويسنده , , Baoqing Ma، نويسنده , , Michael J. Sofia، نويسنده , , Samuel W. Gerritz، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2008
Abstract :
The discovery and optimization of a novel series of prolinol-derived GHSR agonists is described. This series emerged from a 11,520-member solid-phase library targeting the GPCR protein superfamily, and the rapid optimization of low micromolar hits into single-digit nanomolar leads can be attributed to the solid-phase synthesis of matrix libraries, which revealed multiple non-additive structure–activity relationships. In addition, the separation of potent diastereomers highlighted the influence of the α-methyl stereochemistry of the phenoxyacetamide sidechain on GHSR activity.
Keywords :
Solid-phase library , Hit to lead , combinatorial chemistry , Non-linear SAR , GHSR , Growth hormone secretagogue receptor , G-protein coupled receptor , GPCR , Non-additive SAR , solid-phase synthesis , parallel synthesis , GPCR agonist , Matrix library
Journal title :
Bioorganic & Medicinal Chemistry Letters
Journal title :
Bioorganic & Medicinal Chemistry Letters
