Author/Authors :
Sanath K. Meegalla، نويسنده , , Mark J. Wall، نويسنده , , Jinsheng Chen، نويسنده , , Kenneth J. Wilson، نويسنده , , Shelley K. Ballentine، نويسنده , , Renee L. DesJarlais، نويسنده , , Paul B. Sigler and Carsten Schubert، نويسنده , , Carl S. Crysler، نويسنده , , Yanmin Chen، نويسنده , , Christopher J. Molloy، نويسنده , , Margery A. Chaikin، نويسنده , , Carl L. Manthey، نويسنده , , Mark R. Player، نويسنده , , Bruce E. Tomczuk، نويسنده , , Carl R. Illig، نويسنده ,
Abstract :
An anti-inflammatory 1,2,4-phenylenetriamine-containing series of FMS inhibitors with a potential to form reactive metabolites was transformed into a series with equivalent potency by incorporation of carbon-based replacement groups. Structure-based modeling provided the framework to efficiently effect this transformation and restore potencies to previous levels. This optimization removed a risk factor for potential idiosyncratic drug reactions.
Keywords :
cFMS , FMS , M-CSF , Colony-stimulating factor-1 , macrophages , Anti-inflammatory activity , Idiosyncratic drug reactions , CSF-1R
