Synthesis and activities of oxidative metabolites of the anti-arthritic drug candidate S-2474.
We have synthesized and characterized some oxidative metabolites of S-2474. In this study, we discovered a novel skeleton, the 2,3-dihydrobenzofuran derivative, which inhibited PGE(2) production at a very low concentration and was effective in the anti-carrageenin footpad edema assay.
Discovery Research Laboratories, Shionogi & Co., Ltd., Fukushima-ku, 553-0002, Osaka, Japan. masanao.inagaki@shionogi.co.jp
Masanao
M
Inagaki
Hirokuni
H
Jyoyama
Takashi
T
Ono
Katsutoshi
K
Yamada
Mika
M
Kobayashi
Takahiko
T
Baba
Akira
A
Touchi
Kouji
K
Iwatani
Tomoyuki
T
Ohkawa
Saichi
S
Matsumoto
Tatsuo
T
Tsuri
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000494:pharmacology; D003499:Cyclic S-Oxides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004487:Edema / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D013844:Thiazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology
C409872:((E)-(5)-(3,5-di-tert-butyl-4-hydroxybenzylidene)- 2-ethyl-1,2-isothiazolidine-1,1-dioxide); D000893:Anti-Inflammatory Agents; D001572:Benzofurans; D003499:Cyclic S-Oxides; D007375:Interleukin-1; D016859:Lipoxygenase Inhibitors; D013844:Thiazoles; D007975:Leukotriene B4; D015232:Dinoprostone