Analgesic thiab Antipyretic Activities ntawm 4-Hydroxyisophthalic Acid

4-HYDROXYISOPHTHALIO Acidyog cov khoom lag luam los ntawm kev tsim cov salicylic acid los ntawm Kolbe-Schmitt cov tshuaj tiv thaiv thiab tau pom tias yog ib qho tseem ceeb ntawm' cov hmoov av xim av' residues los ntawm sublimation txheej txheem rau purification ntawm salicylic acid1 • Kev soj ntsuam ntawm ib tug raug qauv ntawm' xim av plua plav' Nws tau pom tias muaj 10 feem pua ​​​​ntawm salicylic, 82 feem pua ​​​​ntawm 4-hydroxyisophthalic thiab 3 feem pua ​​​​ntawm 2-hydroxyisophthalic acids, ua ke nrog qee cov khoom siv tsis zoo.

Los ntawm qhov chaw no muaj yog li muaj peev xwm muaj ntau yam ntawm 4-hydroxyisophthalic acid, chemistry uas tau raug tshuaj xyuas raws li ib feem ntawm kev tshawb fawb ntawm Kolbe-Schmitt cov tshuaj tiv thaiv ntawm Chemical Research Laboratory •. Los ntawm kev txiav txim siab ntawm nws cov qauv zoo sib xws rau salicylic acid, nws tau tawm tswv yim ntawm Chemical Research Laboratory tias 4-hydroxyisophthalic acid kuj tseem muaj cov tshuaj pharmacological zoo sib xws. Raws li, nyob rau lub Ob Hlis 1954, kev tshawb fawb tshuaj tau pib ntawm Ware thiab, txij li qhov kev tshawb pom tau zoo, kev tshawb fawb biochemical kuj tau ua.

Hauv kev sim thawj zaug, cov tshuaj tau siv los ntawm txoj hauv kev intraperitoneal, tshuaj aspirin thiab phthalic acid derivatives raug tshem tawm hauv 5 feem pua ​​​​ntawm cov pos hniav acacia. Hauv kev sim tshuaj tua kab mob, ib daim ntawv yooj yim ntawm cov tshuaj tua kab mob ntawm Green, Young thiab Godfrey3 tau siv, uas ntsuas cov lus teb ntawm lub siab, siv rau lub ntsis ntawm tus Tsov tus tw, yuav tsum tau tshem tawm squeak los ntawm ib tug hluas nas. Txoj kev no tau pom tias 4-hydroxyisophthalic acid tsis muaj qhov tsis txaus ntseeg muaj cov khoom siv tshuaj tua kab mob, nws cov koob tshuaj nruab nrab yog 303 ( txwv 261-353) mgm. rau kgm. Hauv kev sib piv nws tau nthuav tawm 4·1 ( txwv 3·2-5·5) ib xees ntawm cov dej num ntawm codeine. Qhov koob tshuaj nruab nrab (LD50) rau cov nas me yog 1,071 ( txwv 968-1,185) mgm. ib kgm., thiab ib koob tshuaj 600 mgm. rau kgm. raug zam los ntawm tag nrho yim caum xya nas uas tau txais nws. Kev sib piv ntawm LD50 ntawm 4-hydroxyisophthalic acid nrog cov ntaub ntawv luam tawm sib xws rau codeine4 qhia tias nws muaj li ntawm 10 feem pua ​​​​ntawm cov tshuaj lom ntawm codeine. Piv nrog rau 4-hydroxyisophthalic acid, aspirin yog ob qho tib si tshuaj lom thiab tsis zoo. LD50 yog 541 (tso 485-603) mgm. ib kgm., thiab ib koob tshuaj 300 mgm. ib kgm., uas tau zam los ntawm tag nrho cov nas, ua tsis tau tej yam analgesic nyhuv, txawm hais tias ntau dua koob tshuaj tshwm sim. Hauv kev sib piv ntawm cov tshuaj tiv thaiv kab mob hauv cov luav, nws tau pom tias 4-hydroxyisophthalic acid tau zoo li cov tshuaj aspirin hauv kev tiv thaiv kev kub taub hau los ntawm kev npaj pyrogen los ntawm Proteus vulgaris.

Txij li thaum 4-hydroxyisophthalic acid tau cog lus tias yuav muaj txiaj ntsig kho mob ntawm ib hom zoo ib yam li, tab sis ntau dua, cov tshuaj aspirin, kev kuaj mob toxicity tau ua los ntawm kev tswj hwm cov tshuaj ntawm 0·5 thiab 1·0 feem pua ​​​​hauv kev noj zaub mov rau cov nas. lub sij hawm ntawm kaum plaub lub lis piam. Hauv qhov kev sim no, nws pom muaj cov tshuaj toxicity tsawg heev, ntawm tib qho kev txiav txim raws li cov tshuaj aspirin, uas tau siv rau kev siv. Kev ntsuam xyuas analgesic kuj tau ua nrog 2-hydroxyisophthalic, phthalic, terephthalic thiab isophthalic acids. 2-hydroxy acid yog hais txog equipotent rau 4-hydroxy, thaum lub unsubstituted acids qhia me ntsis kev ua.

Kev tshawb nrhiav ua ntej ntawm kev tso tawm ntawm 4-hydroxyisophthalic acid los ntawm nas pom tias tsis pub dhau 24 teev. txog 40 feem pua ​​​​ntawm 10-mgm. koob tshuaj tau muab los ntawm lub plab raj tau tawm tsis hloov pauv hauv cov zis thiab li ntawm 25 feem pua ​​​​ntawm cov freces. Cov txheej txheem ntawm kev kwv yees tau ua raws li cov xim liab-liab xim tsim thaum cov kua qaub tso cai rau cov tshuaj ferric nitrate. Acid hydrolysis ua tsis tau kom nce tus nqi ntawm cov dawb 4-hydroxyisophthalic acid, qhia tias tsis muaj qee cov ntaub ntawv conjugated los ntawm cov zis, thaum tsis muaj lwm yam metabolites, xws li salicylic, p-hydroxybenzoic thiab gentisic acids, tau qhia los ntawm daim ntawv. electrophoresis. Kev sim tshuaj ntsuam xyuas los soj ntsuam cov kev siv kho mob tau zoo ntawm cov kev tshawb pom no tab tom ua tiav.