Synthesis of the metabolites of 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide (KRP-197/ONO-8025).
We synthesized the six presumed metabolites (2--7) of 4-(2-methyl-1H-imidazol-1-yl)-2,2-diphenylbutanamide [KRP-197/ONO-8025, 1], a urinary incontinence therapeutic agent, in order to confirm the structures of the metabolites. Metabolite (2) was synthesized via glucuronidaion of compound (1) and methyl 2,3,4-tri-O-benzoyl-1-methanesulfonyl-alpha-D-glucopyranuronate. Metabolite (3) was synthesized via 3-(tert-butoxycarbonyl)-2-methyl-1,3-imidazolidine-4,5-dione. Metabolites (4--7) were synthesized via 4-amino-2-diphenylbutanamide, respectively. The structures of the metabolites (2--7) in humans were identified by means of synthesis of the authentic compounds.
Araya
Ichiro
I
Research Center, Kyorin Pharmaceutical Co., Ltd, Nogi, Tochigi, Japan. ichirou.araya@mb.kyorin-pharm.co.jp
Tsubuki
Takeshi
T
Saito
Tatsuhiro
T
Numata
Makoto
M
Akita
Hiroyuki
H
D000818:Animals; D006801:Humans; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000138:chemical synthesis / Q000737:chemistry
D007093:Imidazoles; D018727:Muscarinic Antagonists; C120953:imidafenacin