Author/Authors :
Keith P. Moore، نويسنده , , Hong Zhu، نويسنده , , Hemaka A. Rajapakse، نويسنده , , Georgia B. McGaughey، نويسنده , , Dennis Colussi، نويسنده , , Eric A. Price، نويسنده , , Sethu Sankaranarayanan، نويسنده , , Adam J. Simon، نويسنده , , Nicole T. Pudvah، نويسنده , , Jerome H. Hochman، نويسنده , , Timothy Allison، نويسنده , , Sanjeev K. Munshi، نويسنده , , Samuel L. Graham، نويسنده , , Joseph P. Vacca، نويسنده , , Philippe G. Nantermet، نويسنده ,
Abstract :
This letter describes replacements for the P3 amide moiety present in previously reported tertiary carbinamine macrolactones. Although P-gp efflux issues associated with these amide-macrolactones were solved and full brain penetration was measured in one case, potency was compromised in the process.
Keywords :
Glycine 230 , Macrolactone , Negishi coupling , 10s loop , Macrocyclic N-arylation , Tertiary carbinamine , BACE-1 , Alzheimer’s Disease , P-gp efflux pump
