Title of article :
2-Alkylamino- and alkoxy-substituted 2-amino-1,3,4-oxadiazoles—O-Alkyl benzohydroxamate esters replacements retain the desired inhibition and selectivity against MEK (MAP ERK kinase)
Author/Authors :
Joseph S. Warmus، نويسنده , , CathlinFlamme، نويسنده , , Lu Yan Zhang، نويسنده , , Stephen Barrett، نويسنده , , Alexander Bridges، نويسنده , , Huifen Chen، نويسنده , , Richard Gowan، نويسنده , , Michael Kaufman، نويسنده , , Judy Sebolt-Leopold، نويسنده , , Wilbur Leopold، نويسنده , , Ronald Merriman، نويسنده , , Jeffrey Ohren، نويسنده , , Alexander Pavlovsky، نويسنده , , Sally Przybranowski، نويسنده , , Haile Tecle، نويسنده , , Heather Valik، نويسنده , , Christopher Whitehead، نويسنده , , Erli Zhang، نويسنده ,
Abstract :
This paper reports a second generation MEK inhibitor. The previously reported potent and efficacious MEK inhibitor, PD-184352 (CI-1040), contains an integral hydroxamate moiety. This compound suffered from less than ideal solubility and metabolic stability. An oxadiazole moiety behaves as a bioisostere for the hydroxamate group, leading to a more metabolically stable and efficacious MEK inhibitor.
Keywords :
Oxadiazole , Hydroxamic ester , MEK , MAP ERK kinase , Bioisostere , CI-1040
