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Synthesis and evaluation of homo-bivalent GnRHR ligands.

Abstract：

:G protein coupled receptors (GPCRs) are important drug targets in pharmaceutical research. Traditionally, most research efforts have been devoted towards the design of small molecule agonists and antagonists. An interesting, yet poorly investigated class of GPCR modulators comprise the bivalent ligands, in which two receptor pharmacophores are incorporated. Here, we set out to develop a general strategy for the synthesis of bivalent compounds that are projected to bind to the human gonadotropin-releasing hormone receptor (GnRHR). Our results on the dimerisation of a known GnRHR antagonist, with as key step the Huisgen 1,3-cycloaddition, and their ability to bind to and antagonize GnRH-induced GnRHR stimulation, are presented here.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Bonger KM,van den Berg RJ,Heitman LH,IJzerman AP,Oosterom J,Timmers CM,Overkleeft HS,van der Marel GA

doi

10.1016/j.bmc.2007.04.065

subject

Has Abstract

pub_date

2007-07-15 00:00:00

pages

4841-56

issue

14

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(07)00392-6

journal_volume

15

pub_type

杂志文章

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