Kev tsim kho thiab cov khoom ntawm 2,6-dihydroxy-3-methylpurine yog dab tsi?
Ib tus neeg pab purine ib txwm nrog cov ntawv qhia ua ke C6H6N4O2 yog oxypurinol, lossis2, 6-Dihydroxy-3-methylpurine. Nws txoj kev txhim kho sub-atomic tswj cov purine cov zej zog hydroxyl bundles tsim ntawm 2 thiab 6 txoj haujlwm, koom nrog methyl pob ntawm 3 txoj haujlwm. Raws li kev pom dav dav xws li hypoxanthine, oxipurinol hloov pauv los ntawm qhov muaj cov hydroxyl ntxiv-ua ke.
Oxipurinol yog ib qho metabolite ntawm allopurinol, uas yog siv los kho hyperuricemia thiab gout. Allopurinol mus dhau los ntawm kev pib oxidation rau thav duab oxypurinol, uas yog tsim nyog los ntawm kev ntxiv oxidation los ua oxipurinol. Txoj kev metabolic no qhia pom kev pom rau txoj haujlwm uas oxipurinol ua si hauv cov tshuaj pharmacological ntawm allopurinol.
Oxipurinol, ib qho metabolite ntawm allopurinol, txhim kho cov tshuaj tiv thaiv, tshwj xeeb tshaj yog txo qis uric acid ua rau muaj kev puas tsuaj xws li gout. Vim tias nws qhov tseem ceeb zoo sib xws rau hypoxanthine, oxipurinol tuaj yeem tswj tau lub zog xanthine oxidase tiag tiag, uas tau kaw nrog kev ua rau uric puas. Qhov no alleviates hyperuricemia-txog cov kev mob tshwm sim.
Thaum tsis ntseeg, oxipurinol cia siab tias yuav yog ib feem tseem ceeb hauv cov tshuaj pharmacological ntawm allopurinol, uas qhia txog nws qhov tseem ceeb hauv kev koom tes ntawm gout thiab lwm yam mob uas tau piav qhia los ntawm kev nce qib uric.
Oxipurinol qhia ob peb yam khoom pom tseeb uas ntxiv rau nws cov tshuaj pharmacological thiab sensibility raws li kev kho mob rau cov mob xws li gout:
Kev Tiv Thaiv Xanthine Oxidase: Oxipurinol mus tej zaum yog ib qho teeb meem loj inhibitor ntawm lub impetus xanthine oxidase, tiag tiag cuam tshuam qhov kev hloov ntawm hypoxanthine rau xanthine thiab ntxiv rau uric puas. Oxipurinol txo qis qib uric corrosive hauv lub cev los ntawm kev cuam tshuam lub voj voog enzymatic, tom qab ntawd txo qis cov tsos mob thiab kev phiv ntawm hyperuricemia thiab gout.
Yam Ntxim Saib Ntxim Ua:2, 6-Dihydroxy-3-methylpurineqhia tau tias yog hmoov dawb ntawm chav tsev kub. Nws muaj 288-290 degree softening point uas yog siab me ntsis. Nws txoj kev cia siab thiab kev yooj yim ntawm kev cuam tshuam nrog hauv cov phiaj xwm tshuaj yog qhov tshwm sim ntawm cov khoom zoo no.
Kev Tiv Thaiv UV: Oxipurinol muaj qhov siab tshaj UV ingestion ntawm 260 nm, yog li cov tswv yim pom zoo tuaj yeem siv los txheeb xyuas thiab ntsuas nws.
Solubility: Oxipurinol lub peev xwm yaj hauv dej thiab cov kuab tshuaj polar xws li ethanol ua rau nws yog ib tus neeg sib tw zoo rau kev siv tshuaj. Txawm li cas los xij, nws tsis txaus soluble hauv cov kuab tshuaj tsis muaj polar xws li diethyl ether.
pKa qhov tseem ceeb: pKa qhov muaj peev xwm nce ntawm oxipurinol, ntsuas ntawm 7.4 thiab 11.8, qhia nws cov ionization lead thiab protonation xeev nyob rau hauv cov pH sib txawv, uas tuaj yeem cuam tshuam nws cov tshuaj pharmacokinetics thiab pharmacodynamics.
Feem ntau hais lus, oxipurinol tuaj yeem sib tw endogenous substrates rau kev txwv rau xanthine oxidase nyob rau hauv lub teeb ntawm nws cov ntsiab lus, piv txwv li, nws hydroxyl sib sau ua ke thiab ze rau purine bases. Qhov no, koom nrog nws lub cev thiab cov khoom siv, ua rau oxipurinol haum rau kev siv los ua cov metabolic subordinate ntawm allopurinol hauv kev kho mob gout thiab lwm yam mob uas tau piav qhia los ntawm kev nce qib uric puas tsuaj.
oxipurinol zoo li cas los ntawm allopurinol?
Allopurinol, uas yog lwm yam hu ua Zyloprim, yog thawj zaug hloov mus rau hauv oxypurinol ua ntej ntxiv rau oxidized rau hauv oxipurinol. Ntawm no yog ib daim duab ntawm yuav ua li cas oxipurinol yog framed los ntawm allopurinol:
1. Kev noj ntawm qhov ncauj: Allopurinol nkag mus rau hauv cov qauv kwj dej tom qab tawm hauv plab hnyuv thaum noj qhov ncauj.
2. Ua ib txoj hauv kev rau oxypurinol: Hauv daim siab thiab cov ntaub so ntswg sib txawv, xanthine oxidase sai hloov allopurinol rau hauv oxypurinol. Qhov no yog tag nrho enamoring metabolite.
3. Ntxiv oxidation rau oxipurinol: Oxypurinol yog ntxiv rau oxidized rau hauv lub xeem muaj zog metabolite oxipurinol, rau feem ntau hu ua2, 6-Dihydroxy-3-methylpurine. Qhov no tshwm sim los ntawm hydroxylation ntawm 2 thiab 6 qhov chaw ntawm lub nplhaib purine.
4. Kev txwv ntawm cov protein: Oxipurinol forestalls kev txhim kho ntawm uric corrosive los ntawm kev mus ua ib tug haib inhibitor ntawm xanthine oxidase.2, 6-Dihydroxy-3-methylpurinemuaj tag nrho cov proclivity siab dua rau xanthine oxidase tshaj oxypurinol los yog allopurinol.
5. Kev tso tawm: Ob leeg oxypurinol thiab oxipurinol yog dej ntau dua li allopurinol, yog li lawv yog cov xa tawm sai dua. Qhov ib nrab ntawm oxipurinol nyob ib ncig ntawm 15 teev.
Txhawm rau ua kom tiav, thaum xanthine oxidase oxidizes allopurinol ob zaug ua ke, nws tsim cov dynamic metabolite oxipurinol. Cov lus teb hydroxylation ua rau muaj feem cuam tshuam nrog purine kom meej meej tswj cov protein ntau uas tso tawm allopurinol.
Dab tsi yog txoj hauv kev biosynthesis rau oxipurinol?
Tsis yog biosynthesized ib txwm los ntawm lub cev, oxypurinol yog tsim los ua cov metabolite ntawm cov tshuaj allopurinol. Txoj kev biosynthetic yog txuam nrog ob los yog peb cov lus teb enzymatic:
1. Kev noj tshuaj ntawm allopurinol: Allopurinol yog tswj los ntawm qhov ncauj thiab noj rau hauv cov qauv dissipating.
2.Hydroxylation: Xanthine oxidase hydroxylates allopurinol ntawm txoj hauj lwm 2, nqa txog kev npaj ntawm oxypurinol.
3.Ring Qhib: Ib qho nruab nrab 4-hydroxypurine compound yog tsim thaum lub nplhaib pyrazole ntawm oxypurinol qhib.
4.Methylation: Ib pob methyl ntxiv rau 4-hydroxypurine tsom rau ntawm 3 txoj haujlwm.
5. Ntxiv Hydroxylation:2, 6-Dihydroxy-3-methylpurine, feem ntau hu ua oxipurinol, yog xa tawm thaum lub pob hydroxyl ntxiv rau qhov chaw methylated ntawm txoj hauj lwm 6 los ntawm xanthine oxidase.
6.Enzyme Limitation: Oxipurinol ua raws li kev pheej hmoo inhibitor ntawm xanthine oxidase, tiv thaiv kev hloov pauv ntawm hypoxanthine rau xanthine thiab uric puas.
Txawm hais tias tsis yog ncaj qha biosynthesized, oxypurinol yog tsim los ntawm kev siv allopurinol los ntawm kev nce qib ntawm cov tshuaj catalyzed hydroxylation thiab cov lus teb methylation. Cov metabolite tom ntej mus feem ntau yuav yog cov khoom inhibitor ntawm xanthine oxidase, thaum kawg txo qis uric horrendous qib hauv lub cev. Lub voj voog no qhia txog kev hloov pauv ntawm prodrug rau hauv kev ua haujlwm inhibitor ntawm endogenous metabolic txoj hauv kev.
Cov ntaub ntawv:
Hnub, RO, Miners, JO, Birkett, DJ, Whitehead, A., Naidoo, D., Hayes, J., & Graham, GG (1988). Allopurinol metabolism thiab oxypurinol concentrations hauv ib txwm kawm. British phau ntawv Journal of Clinical Pharmology, 26(2), 235–242.
Elion, GB (1989). Txoj kev purine rau chemotherapy. Science (New York, NY), 244(4900), 41–47.
Mandala, A., McKay, W., Ashby, D., & Belcher, J. (2020). Allopurinol. [Hloov kho 2022 Nov 13]. Hauv: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Peb -. Muaj los ntawm:
Pacher, P., Nivorozhkin, A., & Szabó, C. (2006). Kev kho cov teebmeem ntawm xanthine oxidase inhibitors: renaissance ib nrab xyoo tom qab nrhiav pom ntawm allopurinol. Pharmacological xyuas, 58(1), 87–114.
Yog li, A., & Thorens, B. (2010). Uric acid thauj thiab kab mob. Phau ntawv Journal of Clinical Research, 120(6), 1791–1799.