Weixu Zhai,
Neil Flynn,
Daniel A Longhi,
Joseph A Tino,
Brian J Murphy,
Dorothy Slusarchyk,
David A Gordon, Anna Pendri,
Shuhao Shi,
Robert Stoffel,
Baoqing Ma,
Michael J Sofia,
Samuel W Gerritz
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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 alpha-methyl stereochemistry of the phenoxyacetamide sidechain on GHSR activity.
Bioorganic & medicinal chemistry letters 09/2008; 18(18):5083-6. · 2.65 Impact Factor
