Author/Authors :
Walter Yu، نويسنده , , Jeffrey M. Dener، نويسنده , , Daniel A. Dickman، نويسنده , , Paul Grothaus، نويسنده , , Yun-Ling Zheng، نويسنده , , Liang Liu، نويسنده , , Chris Havel، نويسنده , , Kimberly Malesky، نويسنده , , Tania Mahajan، نويسنده , , Colin O’Brian، نويسنده , , Emma J. Shelton، نويسنده , , David Sperandio، نويسنده , , Zhiwei Tong، نويسنده , , Robert Yee، نويسنده , , Joyce J. Mordenti، نويسنده ,
Abstract :
The metabolites of the tryptase inhibitor CRA-9249 were identified after exposure to liver microsomes. CRA-9249 was found to be degraded rapidly in liver microsomes from rabbit, dog, cynomolgus monkey, and human, and less rapidly in microsomes from rat. The key metabolites included cleavage of an aryl ether, in addition to an unexpected hydroxylation of the amide side chain adjacent to the amide nitrogen. The chemical structures of both metabolites were confirmed by synthesis and comparison to material isolated from the liver microsomes. Several suspected hydroxylated metabolites were also synthesized and analyzed as part of the structure identification process.
Keywords :
Metabolism , Metabolite identification , synthesis , Active metabolite
