title: 2-[3-(1,1-Dimethylethyl)-5-methoxyphenyloxazolo[4,5-b]pyridine, a new topical antiinflammatory and analgesic compound lacking systemic activity and gastric side effects.
abstract: The substituted oxazolopyridine 2-[3-(1,1-dimethylethyl)-5-methoxyphenyl]oxazolo[4,5-b]pyridine (OZP) inhibits phorbol myristate acetate-induced increases in vascular permeability and neutrophil accumulation in rat ears with ED50 of 253 and 200 micrograms, respectively. This compound is as potent as indomethacin to inhibit UV-induced erythema in guinea pig skin and is an effective analgesic when applied topically to the rat footpad in the yeast hyperalgesia model. OZP is a cyclooxygenase inhibitor with an IC50 of 0.06 mumol/l and inhibits prostaglandin E2, but not leukotriene C4 synthesis, by mouse peritoneal macrophages. This compound is inactive in the carrageenan paw edema assay at 90 mg/kg when administered orally or intraperitoneally, but is effective when injected into the paw. OZP is not a contact allergen and does not cause gastric irritation in rats at doses up to 180 mg/kg orally. OZP is rapidly metabolized by rat liver microsomes in a concentration and time dependent manner. Furthermore, when administered orally, OZP is cleared rapidly in rats with plasma levels being detected only at 5 and 30 min following a 2 mg/kg dose. There was no drug in the gastrointestinal tract of rats 3 h after an oral dose. Thus, this compound appears to be a new, potent and safe topical antiinflammatory and an analgesic agent lacking systemic effects.
mesh_terms: D000700:Analgesics; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000517:prevention & control; D004890:Erythema / Q000517:prevention & control; D005260:Female; D006099:Granuloma / Q000517:prevention & control; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D011725:Pyridines / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012669:Seminal Vesicles / Q000378:metabolism; D013276:Stomach Ulcer / Q000139:chemically induced
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D011725:Pyridines; C045915:2-(3-(1,1-dimethylethyl))-5-methoxyphenyloxazolo(4,5-b)pyridine