- Synthesis and structure activity relationship studies of benzothieno[3,2-b]furan derivatives as a novel class of IKKβ inhibitors
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As a novel class of IKKβ inhibitors, a series of tricyclic furan derivatives was designed and synthesized based on the structure of known thiophene IKKβ inhibitors. Among the various fused furan derivatives synthesized, a benzothieno[3,2-b]furan derivative 13a displayed potent inhibitory activity towards IKKβ in enzymatic and cellular assays. The potent inhibitory activity originates from an intramolecular non-bonded S...O interaction which was confirmed by the X-ray structure of JNK3 with 16k. The introduction of further substituents on the core structure led to the discovery of the 6-alkoxy derivatives, which possessed a comparable IKKβ inhibitory activity to 13a and an improved metabolic stability. Among these, appropriately lipophilic compounds 16a, h, i, and 13g (logD>2) were found to possess good oral bioavailability.
- Sugiyama, Hideyuki,Yoshida, Masato,Mori, Kouji,Kawamoto, Tomohiro,Sogabe, Satoshi,Takagi, Terufumi,Oki, Hideyuki,Tanaka, Toshimasa,Kimura, Hiroyuki,Ikeura, Yoshinori
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p. 613 - 624
(2008/02/13)
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- Analgesic compositions consisting of 2H-benzothieno[3,2-c]pyrazol-3-amine derivatives
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Herein is disclosed 2H-benzothieno[3,2-c]pyrazol-3-amine derivatives, therapeutically acceptable acid addition salts thereof, processes for their preparation, methods of using the derivatives and pharmaceutical compositions. The derivatives are useful for
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