Ondansetronyog ib qho kev xaiv 5-HT3 receptor antagonist nrog cov tshuaj npe N-(2-methoxy-1H-pyrrol-3-yl)-1,2,3,{ {10}}tetrahydro-9-methanol Cyl-3-(2-methylpropyl)-4H-oxyquinolin-4-ib qho, cov mis mos molecular yog C18H19N3O, qhov hnyav molecular yog 293.37, CAS tus lej yog 99614-02-5. Nws cov tsos yog dawb los yog daj me ntsis hmoov, yooj yim soluble nyob rau hauv dej thiab methanol, nrog zoo stability, thiab muaj peev xwm tswj tau nws cov nyhuv tshuaj rau lub sij hawm ntev thaum khaws cia nyob rau hauv qhuav tej yam kev mob. Raws li ib tug 5-HT3 receptor antagonist, Ondansetron tuaj yeem cuam tshuam cov 5-HT3 receptors hauv plab hnyuv thiab txo qhov xeev siab thiab ntuav. Nws lub luag haujlwm tseem ceeb ntawm kev ua haujlwm yog txhawm rau tiv thaiv 5-HT3 receptors ntawm phab ntsa plab hnyuv kom tsis txhob raug txhawb los ntawm 5-HT cov tshuaj tso tawm hauv lub cev, yog li txo cov tsos mob ntawm xeev siab thiab ntuav.
Tam sim no, Ondansetron tau siv dav hauv kev kho mob xeev siab thiab ntuav tshwm sim los ntawm kev ntuav tom qab ntuav thiab tshuaj kho mob, thiab tseem siv rau hauv kev kho mob xeev siab thiab ntuav los ntawm kev kho hluav taws xob, xeev siab thiab ntuav los ntawm ntuav thaum cev xeeb tub lig thiab ntuav los ntawm kev hnoos. zog.
Daim ntawv thov ntawm Ondansetron muaj cov yam ntxwv hauv qab no:
1. Kev yooj yim ntawm kev siv: Ondansetron tuaj yeem siv ntau txoj hauv kev xws li kev tswj hwm qhov ncauj, kev txhaj tshuaj intramuscular, thiab txhaj tshuaj intravenous, thiab siv tau yooj yim.
2. Ua tau zoo thiab nyab xeeb: Ondansetron muaj txiaj ntsig zoo thiab nyab xeeb, thiab tsis tshua muaj tshwm sim thaum kho.
3. Kev kho ntau yam: Ondansetron tsis tuaj yeem kho cov tsos mob xws li xeev siab thiab ntuav, tab sis kuj tuaj yeem siv los kho xeev siab thiab ntuav cov tsos mob tshwm sim los ntawm lwm yam kab mob, xws li xeev siab los ntawm cov tshuaj antiepileptic, xeev siab los ntawm subacute leukemia chemotherapy, thiab lwm yam. .
4. tuaj yeem siv los ua kev kho mob ntxiv: Ondansetron tuaj yeem siv los ua kev kho mob ntxiv rau lwm yam kev kho mob, xws li kev kho hluav taws xob thiab tshuaj khomob, kom txo tau nws cov kev mob tshwm sim ntawm xeev siab thiab ntuav.
Nyob rau hauv xaus, Ondansetron yog ib tug nquag siv xaiv 5-HT3 receptor antagonist, uas yuav siv tau los kho ntau yam tsos mob ntawm xeev siab thiab ntuav, thiab yog dav siv nyob rau hauv cov tshuaj kho mob.
Lub architecture ntawm Ondansetron yog raws li nram no:
Ib txoj hauv kev zoo ondansetron synthesis yuav tsum suav nrog ntau cov kauj ruam, xws li xaiv cov substrates tsim nyog, ligands, tej yam kev mob, thiab lwm yam. Cov txheej txheem hluavtaws ntawm ob peb isomers ntawm Ondansetron yuav qhia hauv qab no.
Thawj txheej txheem hluavtaws ntawm Ondansetron:
Txoj kev dav dav rau kev sib txuas ntawm Ondansetron yog ua kom hnov mob 4-phenoxycarboxamide-2,3,5,6-tetrahydroimidazole nrog kev sib xyaw ntawm txhuas trichloride thiab sulfonyl chloride. Cov khoom uas tau tshwm sim yog reacted nrog 2-chloro-1-cyclopropylformamide, uas nyob rau hauv lem decarboxylates lub compound nrog phthalic anhydride thiab tsim cov Ondansetron. Txoj kev no tuaj yeem tau txais Ondansetron nyob rau hauv ib qho kev tawm los, tab sis nws kuj tseem nrog cov teeb meem ntawm cov khoom pov tseg thiab cov nqi siab.
Qhov thib ob synthesis txoj kev ntawm Ondansetron:
Cov neeg xws li TLDavies tau tshaj tawm lwm hom kev sib xyaw ntawm Ondansetron, thiab cov kauj ruam ua tiav yog raws li hauv qab no:
Ua ntej, acetylacetone tau hloov mus rau 3-bromo-5, 5-dimethylcyclohexane-1, 2-dione los ntawm cov tshuaj tiv thaiv nucleophilic hloov pauv. Tom qab ntawd, los ntawm kev tswj cov pH, lub diketone raug txo mus rau cov cawv sib xws thiab hnov mob nrog ethyl N-phenylnitrosobutyrate nyob rau hauv cov pa roj-theem chlorinated thionyl chloride / siab boiling point hnyav sib tov. Cov khoom tau dhau los ua cov tshuaj tiv thaiv txiv neej hydrazide, thiab tom qab ntawd nkag mus rau Hydrodehalogenation cov tshuaj tiv thaiv los tsim Ondansetron. Txoj kev no muaj cov txiaj ntsig tseem ceeb xws li cov pov tseg tsawg dua, tsis tas yuav tsum muaj aluminium trichloride thiab siab yield.
Qhov thib peb synthesis txoj kev ntawm Ondansetron:
Tsis tas li ntawd, Nenad et al. tshaj tawm ib txoj kev tshiab rau ib-kauj ruam synthesis ntawm Ondansetron los ntawm flutecavir precursors, uas yog, synthesis ntawm Ondansetron los ntawm ib kauj ruam cov tshuaj tiv thaiv catalyzed los ntawm Tanzanian liab FGL52 phosphate. Txoj kev tshuaj tiv thaiv tshwj xeeb yog: txoj kev no muaj qhov zoo ntawm kev nkag tau yooj yim rau cov ntaub ntawv raw, lub sijhawm luv luv, thiab cov txiaj ntsig siab.
Plaub txheej txheem hluavtaws ntawm Ondansetron:
Andrási et al. tshaj tawm txoj kev yooj yim thiab ceev ceev rau kev sib txuas ntawm Ondansetron. Txoj kev no siv 4-hydroxy-2,3,5,6-tetrahydroimidazole ua cov khoom pib, thiab ua cov tshuaj hloov pauv, thaum kawg tau Ondansetron. Cov kauj ruam tshwj xeeb yog: condense 4-hydroxy-2, 3,5, 6-tetrahydroimidazole nrog isoamyl cawv los ua isoamyl compound, thiab ua acylation cov tshuaj tiv thaiv ntawm cov tshuaj no nrog acetylacetone, thiab tom qab ntawd ua carboxylated rau hauv acid anhydride lub cev, thiab thaum kawg tsim Ondansetron los ntawm ib tug series ntawm txo thiab cua kub tshwm sim. Txoj kev muaj qhov zoo ntawm cov tshuaj tiv thaiv me me, txoj hauv kev yooj yim thiab muaj txiaj ntsig zoo.
Ondansetron yog ib qho tseem ceeb heev digestive system antiemetic tshuaj. Muaj ntau txoj hauv kev zoo rau cov tshuaj no, xws li acetylacetone txoj kev, nucleophilic hloov cov tshuaj tiv thaiv txoj kev, hybridization cov tshuaj tiv thaiv thiab lwm yam. Txawm li cas los xij, tseem muaj qee qhov teeb meem hauv kev sib txuas ntawm Ondansetron, xws li kev siv cov catalysts, kev tsim cov khoom lag luam hauv cov tshuaj tiv thaiv, thiab cov txheeb ze complexity ntawm cov txheej txheem. Yog li ntawd, kev tshawb fawb tob ntxiv thiab kev ua kom zoo ntawm txoj kev sib txuas ntawm Ondansetron tseem xav tau los ua kom tau raws li qhov xav tau ntawm kev kho mob.
Ondansetron yog ib qho 5-HT3 receptor antagonist uas tuaj yeem siv los tiv thaiv thiab kho xeev siab thiab ntuav cuam tshuam nrog kev kho hluav taws xob thiab tshuaj khomob. Nws tau tsim los ntawm lub tuam txhab tshuaj British nto moo GlaxoSmithKline. Hauv qab no yog keeb kwm kev tshawb pom ntawm Ondansetron:
Thaum ntxov xyoo 1980s, pab pawg tshawb fawb thiab kev tsim kho ntawm GlaxoSmithKline pib kawm cov metabolites zog tshiab, vam tias yuav tsim cov tshuaj tshiab rau xeev siab thiab ntuav. Hauv ib txoj kev tshawb fawb, cov kws tshawb fawb tau txheeb xyuas qhov 5-HT3 receptor qhia hauv plab hnyuv epithelial hlwb, ib qho ion channel uas cuam tshuam nrog lwm cov ion channel receptors xws li choline receptors thiab amide receptors zoo ib yam.
Xyoo 1984, pab pawg tshawb fawb tau sim nrog txoj hnyuv plab hauv cov nas thiab txheeb xyuas lub luag haujlwm ntawm 5-HT3 receptor hauv kev tswj cov xeev siab thiab ntuav. Pab pawg kuj tau txheeb xyuas qee cov tshuaj sulfonythiazole, uas muaj peev xwm inhibit 5-HT3 receptors. Cov sulfonythiazoles tau pom sai sai tias yog cov khoom cog lus zoo tshaj plaws rau kev tiv thaiv xeev siab thiab ntuav.
Xyoo 1987, pab pawg tshawb fawb tau xaiv ib qho chaw los ntawm ntau txhiab sulfonythiazole tebchaw. Cov tshuaj no tau pom tias muaj zog inhibitory nyhuv nyob rau hauv ntuav kev sim ntawm cov nas thiab nas, thiab nws muaj zog inhibitory nyhuv dua li lwm cov tebchaw. High affinity thiab ntau dua selectivity. Tom qab ntawd, ntau qhov kev sim hauv vivo thiab hauv vitro tau ua los txheeb xyuas cov teebmeem pharmacological, metabolic kinetics thiab toxicological zog ntawm cov tshuaj no, thiab nws tau pom tias nws muaj kev nyab xeeb pharmacological.
Nyob rau hauv 1988, lub compound yog hu ua Ondansetron thiab kuj patented los ntawm GlaxoSmithKline. Ob xyoos tom qab, FDA pom zoo cov tshuaj, ua tiav kev txhim kho ntawm Ondansetron. Txij thaum ntawd los, Ondansetron tau siv dav hauv kev kho hluav taws xob thiab tshuaj tua kab mob ntsig txog xeev siab thiab ntuav, thiab suav tias yog ib qho tshuaj zoo tshaj plaws rau kev kho tus mob no.