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Document Figure 14 2-Dimensional structures of small molecules that exhibit IL-1 modulating activities. They are tenidap, ciprofloxacin, 3-Deazaadenosine, (SK&F 86002), E5110, DMARDs (Chloroquine, Auranofin, Sodium aurothiomalate and Dexamethasone) tiaprofenic acid, dexamethasone, tricyclic-ylidene-acetic acid and its derivative, Probucol, eicosapentenoic acid + docosahexenoic, pentoxifylline, Denbufylline, and Romazarit (Ro-31-3948). http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_422.html (1 of 2) [4/5/2004 5:49:57 PM] Page 422
Document Page 423 American Home Products has patented molecules ranging from substituted quinoline, piperidine, and naphthpyridine compounds as immunomodulators. Ciprofloxacin, a quinolone antibiotic, reduced the extracellular IL-1 activity in human monocytes and delayed the peak production of IL-1α IL-β by 24 h and decreased total IL-1β production, but did not change total IL-1α production [75,76]. Tenidap, an antiarthritic drug, has shown efficacy both in rheumatoid arthritis and osteoarthritis [77,78]. It is a known inhibitor of 5-lipoxygenase and cyclooxygenase (5-LO/CO) and in vitro studies indicate that it also inhibits the synthesis of mature IL-1 and pro IL-1 [77,79]. Kadin reports analogs of Tenidap as antiinflammatory agents and analgesics [80]. An antiarthritic molecule, 3- Deazaadenosine, has been demonstrated to inhibit IL-1 production by LPS- stimulated human PBMCs acting at the level of RNA synthesis and also by blocking the effects of IL-1α on EL4 cells and induction of PGE 2 release by human fibroblast [81,82]. Another 5-LO/CO inhibitor (SK&F 86002) has been reported to inhibit the synthesis of IL-1 in human monocytes and human synovial cells in a dose-dependent manner [83,84]. Analogs of this compound http://legacy.netlibrary.com/nlreader/nlReader.dll?bookid=12640&filename=Page_423.html [4/5/2004 5:50:16 PM]
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Document 122. Marshall WS, Beaton G
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Document dine) and didanosine (dide
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Document [Protease targets] serinyl
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