Discovery and optimization of (R)-prolinol-derived agonists of the Growth Hormone Secretagogue receptor (GHSR).

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.

journal_name

Bioorg Med Chem Lett

authors

Zhai W,Flynn N,Longhi DA,Tino JA,Murphy BJ,Slusarchyk D,Gordon DA,Pendri A,Shi S,Stoffel R,Ma B,Sofia MJ,Gerritz SW

doi

10.1016/j.bmcl.2008.07.120

subject

Has Abstract

pub_date

2008-09-15 00:00:00

pages

5083-6

issue

18

eissn

0960-894X

issn

1464-3405

pii

S0960-894X(08)00906-2

journal_volume

18

pub_type

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