1.
Bioorg Med Chem Lett
; 19(7): 2075-8, 2009 Apr 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-19250823
RESUMEN
Sulfonamides, exemplified by 3a, were identified as highly selective EP(2) agonists. Lead optimization led to the identification of CP-533536, 7f, a potent and selective EP(2) agonist. CP-533536 demonstrated the ability to heal fractures when administered locally as a single dose in rat models of fracture healing.
Asunto(s)
Osteogénesis/efectos de los fármacos , Piridinas/química , Receptores de Prostaglandina E/agonistas , Animales , Masculino , Piridinas/administración & dosificación , Piridinas/farmacocinética , Ratas , Ratas Sprague-Dawley , Receptores de Prostaglandina E/metabolismo , Subtipo EP2 de Receptores de Prostaglandina E , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Sulfonamidas/química , Sulfonamidas/farmacología
2.
Bioorg Med Chem Lett
; 16(7): 1799-802, 2006 Apr 01.
Artículo
en Inglés
| MEDLINE
| ID: mdl-16442794
RESUMEN
Heptanoic acid lactams, exemplified by 2, were identified as highly selective EP4 agonists via high throughput screening. Lead optimization led to the identification of lactams with a 30-fold increase in EP4 potency in vitro. Compounds demonstrated robust bone anabolic effects when administered in vivo in rat models of osteoporosis.
