TABLE 6

Mass spectral analysis of brivanib metabolites detected in rats, monkeys, and humans

Metabolites M7, M25, M26, and M28 were further characterized by NMR. M9 and M31 were further characterized using synthetic standards.

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Metabolite[M + H]+Major FragmentMetabolic Pathway(s)Species
Brivanib371353, 313, 164Rat, monkey, human
M2489313, 285, 175, 164O-Dealkylation, glucuronidationRat, monkey, human
M6393313, 285, 175, 164O-Dealkylation, sulfationRat, monkey, human
M7387369, 329, 311HydroxylationRat, monkey
M9313285, 164, 149O-DealkylationRat, monkey
M13329182, 149O-Dealkylation, hydroxylationRat
M17409329, 311O-Dealkylation, hydroxylation, sulfationMonkey
M19467387, 369, 329Hydroxylation, sulfationRat, monkey, human
M25451371, 353, 313SulfationRat, monkey, human
M26401383, 343CarboxylationRat, monkey, human
M28547371, 353, 313GlucuronidationMonkey, human
M30371313, 148Carboxylation, decarboxylationRat, monkey
M31369312, 148Oxidation to a ketoneRat, monkey, human
M32423343, 325O-Dealkylation, sulfation, carboxylationRat, monkey, human
M33481401, 383, 343Carboxylation, sulfationMonkey, human
M34343325O-Dealkylation, carboxylationRat