Synthesis and Activity of a Metabolite of (S)-6-Amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione (CX-659S)

Yoshiaki Isobe; Masanori Tobe; Osamu Takahashi; Yuso Goto; Yoshifumi Inoue; Fumihiro Obara; Masami Tsuchiya; Hideya Hayashi

doi:10.1248/cpb.50.1418

Notes

Synthesis and Activity of a Metabolite of (S)-6-Amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione (CX-659S)

Yoshiaki Isobe, Masanori Tobe, Osamu Takahashi, Yuso Goto, Yoshifumi Inoue, Fumihiro Obara, Masami Tsuchiya, Hideya Hayashi

Author information

Keywords: CX-659S, metabolite, CHR, ROS, antioxidative activity

JOURNAL FREE ACCESS

2002 Volume 50 Issue 10 Pages 1418-1420

DOI https://doi.org/10.1248/cpb.50.1418

Details

Abstract

CX-659S (1) [(S)-6-amino-5-(6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxamido)-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione], has been developed as a new type anti-inflammatory agent for the treatment of dermatitis. The structure of a major metabolite of CX-659S was determined as (S)-6-amino-5-[2-hydroxy-2-methyl-4-(2,4,5-trimethyl-3,6-dioxo-1,4-cyclohexadienyl)butanamide]-3-methyl-1-phenyl-2,4-(1H,3H)-pyrimidinedione (2) by direct comparison with the synthesized authentic compound. The anti-inflammatory activity of 2 was equipotent with that of 1 on the contact hypersensitivity reaction (CHR) induced by picryl chloride (PC) in mice, suggesting that compound 2 contributes, at least in part, to the anti-inflammatory activity of CX-659S.

Corresponding author

Register with J-STAGE for free!