Substituted terphenyl compounds as the first class of low molecular weight allosteric inhibitors of the luteinizing hormone receptor.
J Med Chem
; 52(7): 2036-42, 2009 Apr 09.
Article
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| MEDLINE
| ID: mdl-19296599
ABSTRACT
The luteinizing hormone (LH) receptor plays an important role in fertility and certain cancers. The endogenous ligands human chorionic gonadotropin (hCG) and LH bind to the large N terminal domain of the receptor. We recently reported on the first radiolabeled low molecular weight (LMW) agonist for this receptor, [(3)H]Org 43553, which was now used to screen for new LMW ligands. We identified a terphenyl derivative that inhibited [(3)H]Org 43553 binding to the receptor, which led us to synthesize a number of derivatives. The most potent compound of this terphenyl series, 24 (LUF5771), was able to increase the dissociation rate of [(3)H]Org 43553 by 3.3-fold (at 10 muM). In a functional assay, the presence of 24 resulted in a 2- to 3-fold lower potency of both Org 43553 and LH. Thus, the compounds presented in this paper are the first LMW ligands that allosterically inhibit the LH receptor.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Compuestos de Terfenilo
/
Receptores de HL
/
Carbamatos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Med Chem
Asunto de la revista:
QUIMICA
Año:
2009
Tipo del documento:
Article
País de afiliación:
Países Bajos