Isoxazolderivate und Verfahren zu deren Herstellung

摘要

1,164,510. Anti-inflammatory &c. compositions. IMPERIAL CHEMICAL INDUSTRIES Ltd; 10 May, 1968 [15 June, 1967], No. 27731/67. Heading A5B. [Also in Division C2] Pharmaceutical compositions having antiinflammatory, analgesic and antipyretic activity comprise, as active ingredient, an isoxazole derivative of the general formula in which Y and Z are each in the 3- or 5- position and wherein Y is a mono- or dihalophenyl group in which the halogen substituent(s) is or are selected from fluorine, chlorine and bromine atoms, and Z is a group of the formula -CR1R2R3, in which R1 and R2 are each a hydrogen atom or a methyl group and R3 is a group of the formula -CO 2 R4 or -CONHR5, in which R4 is a hydrogen atom or a C 1-6 alkyl, phenyl or benzyl group and R5 is a hydrogen atom or an amino or hydroxy group, or a pharmaceutically acceptable salt thereof, together with an inert, pharmaceutically acceptable diluent or carrier and, optionally, at least one known agent having antiinflammatory and/or analgesic activity, e.g. aspirin, paracetamol, codeine, chloroquine, phenylbutazone, oxyphenbutazone, indomethacin, mefenamic acid, flufenamic acid, ibufenac or an anti-inflammatory steroid such as prednisolone. The compositions may be administered in the form of tablets, pills, capsules, suppositories, non-sterile aqueous or non- aqueous solutions or suspensions, sterile injectable aqueous or non-aqueous solutions or suspensions, creams, lotions or ointments. Compositions intended for oral administration optionally also contain at least one anti-cholinergic agent, e.g. homatropine methyl bromide, and/or an antacid, e.g. aluminium hydroxide. Compositions designed for topical application may optionally, in addition, a vasodilating agent, e.g. tolazoline; a vasoconstricting agent, e.g. adrenaline; a local anaesthetic, e.g. amethocaine; a counter-irritant, e.g. capsicum; and/or at least one agent chosen from antibacterial agents, including sulphonamides and antibiotics having antibacterial action, e.g. neomycin; antifungal agents, e.g. hydroxyquinoline; antihistaminic agents, e.g. promethazine; rubefacient agents, e.g. methyl nicotinate; and uricosuric agents, e.g. probenecid. Examples of pharmaceutically acceptable salts are alkali and alkaline earth metal, e.g. sodium or calcium, salts, aluminium and ammonium salts, and salts with pharmaceutically acceptable organic bases of isoxazole derivatives of the above general formula wherein R3 is a carboxy group.