Author/Authors :
Michael J. Breslin، نويسنده , , Mark E. Duggan، نويسنده , , Wasyl Halczenko، نويسنده , , George D. Hartman، نويسنده , , Le T. Duong، نويسنده , , Carmen Fernandez-Metzler، نويسنده , , Michael A Gentile، نويسنده , , Donald B. Kimmel، نويسنده , , Chih-Tai Leu، نويسنده , , Kara Merkle، نويسنده , , Thomayant Prueksaritanont، نويسنده , , Gideon A. Rodan، نويسنده , , Sevgi B. Rodan، نويسنده , , John H Hutchinson، نويسنده ,
Abstract :
Subtle modifications were incorporated into the structure of clinical candidate 1. These changes were designed to maintain potency and selectivity while inducing changes in physical properties leading to improved pharmacokinetics in three species. This approach led to the identification of 4 as a potent, selective αvβ3 receptor antagonist that was selected for clinical development based on an improved PK profile and efficacy demonstrated in an in vivo model of bone turnover.
