1.
J Med Chem
; 47(3): 519-29, 2004 Jan 29.
Artículo
en Inglés
| MEDLINE
| ID: mdl-14736234
RESUMEN
We have previously described a series of antagonists that showed high potency and selectivity for the NK(1) receptor. However, these compounds also had the undesirable property of existing as a mixture of interconverting rotational isomers. Here we show that alteration of the 2-naphthyl substituent can modulate the rate of isomer exchange. Comparisons of the NK(1) receptor affinity for the various conformational forms has facilitated the development of a detailed NK(1) pharmacophore model.
Asunto(s)
Naftalenos/síntesis química , Antagonistas del Receptor de Neuroquinina-1 , Animales , Disponibilidad Biológica , Encéfalo/metabolismo , Línea Celular Tumoral , Perros , Gerbillinae , Humanos , Técnicas In Vitro , Espectroscopía de Resonancia Magnética , Ratones , Modelos Moleculares , Naftalenos/química , Naftalenos/farmacología , Arteria Pulmonar/efectos de los fármacos , Arteria Pulmonar/metabolismo , Conejos , Ensayo de Unión Radioligante , Receptores de Neuroquinina-1/química , Receptores de Neuroquinina-1/metabolismo , Estereoisomerismo , Relación Estructura-Actividad
2.
Bioorg Med Chem Lett
; 15(10): 2503-7, 2005 May 16.
Artículo
en Inglés
| MEDLINE
| ID: mdl-15863305
RESUMEN
Using structure-based design, a new class of inhibitors of protein tyrosine phosphatase-1B (PTP1B) has been identified, which incorporate the 1,2,5-thiadiazolidin-3-one-1,1-dioxide template.