Molnupiravir hmoov CAS 2349386-89-4

Synthesis txoj kev ntawm Molnupiravir

Raws li lub cim tshiab ntawm kev tiv thaiv COVID-19 cov khoom lag luam, Molnupiravir tsis ntev los no tau tshaj tawm los txo qis kev mus pw hauv tsev kho mob thiab kev tuag ntawm cov neeg mob. Cov khoom lag luam muaj qhov zoo ntawm kev ruaj ntseg metabolic, siab bioavailability, siab ntsws faib tus nqi, dav spectrum thiab tsawg toxicity. Lub compound yog Ameslikas tsim los ntawm Merck, thiab txoj kev hluavtaws yog tsim nyob rau hauv 2019. Qhov siab tshaj plaws tawm los tsuas yog 17% hauv tsib kauj ruam. Pab neeg ntawm Xib Fwb Li Zhiyu, Dean ntawm Tsev Kawm Ntawv Pharmacy, Tuam Tshoj Pharmaceutical University, tau tshaj tawm cov lus luv luv hauv 11 qhov teeb meem ntawm English Journal of Pharmacy hauv 2021 los kawm txog cov txheej txheem synthesis ntawm molnupiravir, txhawm rau kom tau txais txoj hauv kev uas yooj yim rau. scale nce, yooj yim rau kev khiav lag luam thiab kev lag luam ntau dua.

Hauv cov txheej txheem tshawb fawb, los ntawm kev tshawb nrhiav cov tshuaj tiv thaiv, qhov tseem ceeb hydroxylamine intermediate tuaj yeem tau los ntawm ib-kauj ruam condensation cov tshuaj tiv thaiv, uas tsis txhob muaj teeb meem ntawm kev ua haujlwm nyuaj thiab tsis tshua muaj txiaj ntsig hauv txoj hauv kev qub. Tsis tas li ntawd, thaum lub sij hawm kawg hydrolysis ntawm kev tiv thaiv pab pawg, tus sau tau pom tias trifluoroacetic acid tuaj yeem tshem tawm acetone diav rawg nrog cov txiaj ntsig siab thiab kev xaiv siab. Cov txheej txheem hluavtaws kawg muaj qhov zoo ntawm cov khoom siv yooj yim, cov tshuaj tiv thaiv me me, kev ua haujlwm yooj yim, cov khoom lag luam siab thiab cov khoom lag luam yooj yim.

cov ntaub ntawv:

Npaj los tiv thaiv SARS-CoV-2 tus neeg sawv cev EIDD-2801 los ntawm txoj hauv kev ua tau zoo thiab muaj peev xwm ua tau, thiab kev ntsuas nrawm ntawm kev kawm tshuab

Zhen Qin, Bin Dong, Renbing Wang, Dechun Huang, Jubo Wang*, Xi Feng, Jinlei Bian*, Zhiyu Li*

Acta Pharm Sin B 2021;11(11):3678-3682

Yuav ua li cas yog lub mechanism ntawm kev txiav txim ntawm Molnupiravir?

Cytosine nucleoside yog cov khoom siv raw rau RNA synthesis.

Molnupiravir hmoovyog ib qho analog ntawm cytosine nucleoside, uas yuav yuam kev rau cytosine nucleoside los ntawm tus kab mob RNA polymerase (RdRp) thiab embedded nyob rau hauv tshiab synthesized RNA, ua rau "txoj kev tuag" ua rau tus kab mob no replicate ntxiv.

Molnupiravir yog tib yam li endogenous cytosine nucleoside.

Molnupiravir thiab nws cov active metabolite (NHC) tsis yog lub ntsiab inhibitors los yog inducers ntawm tshuaj-metabolizing enzymes thiab transporters.

Molnupiravir yog ib qho sib xyaw zoo ib yam li Remdesivir, thiab ob qho khoom ua haujlwm los ntawm kev ua cov ribonucleotides (cov khoom tseem ceeb ntawm RNA molecules). Thaum lub sij hawm tus txheej txheem ntawm tus kab mob replication, cov molecules ntawm cov tshuaj no yuav muab tov rau hauv cov kab mob RNA kab mob los hloov cov nucleic acid puag ib theem zuj zus generated thaum lub sij hawm thawj ib txwm replication ntawm ib co kab mob, ua yuam kev nyob rau hauv lub nucleic acid theem ntawm tus kab mob replication, thiab cov tsub zuj zuj ntawm cov kab mob tuag nucleic acid ua kom raug, uas yog, kev hloov pauv sib txawv, tuaj yeem tiv thaiv tus kab mob rov ua dua tshiab, nthuav dav thiab kis tau.

Qhov txawv ntawm remdesivir, Molnupiravir thiab Paxlovid yog dab tsi?

Tam sim no, muaj peb yam khoom tau lees paub los kho COVID-19 hauv ntiaj teb, uas yog Remdesivir tsim los ntawm Gilead, Molnupiravir tsim los ntawm Merck thiab Paxlovid tsim los ntawm Pfizer. Cov khoom no txhua tus muaj cov tshuaj tiv thaiv kab mob thiab siv los tiv thaiv kev rov ua dua ntawm Covid-19 hauv tib neeg lub cev, tab sis lawv cov tshuaj siv tshuaj sib txawv.

1. Molnupiravir

Molnupiravir hmoovtuaj yeem ua ke nrog A thiab G tib lub sijhawm, yog li nws yuav ua rau kev hloov pauv ntawm tus kabmob tsis raug thiab tig mus rau lwm cov RNA chains. Cov ntaub ntawv kho mob ntawm Molnupiravir tuaj yeem txo cov kab mob hnyav thiab kev tuag ntawm 50%, thiab cov txiaj ntsig zoo. Txawm li cas los xij, qhov kev pheej hmoo ntawm cov khoom no yog tias muaj qee lub caij nyoog ntawm kev hloov pauv mus rau tus kab mob tshiab thiab muaj zog dua tom qab tus kab mob no muaj kev puas tsuaj, thiab cov khoom no kuj tseem tuaj yeem koom nrog DNA rov ua dua qub thiab ua rau muaj kev hloov caj ces hauv tib neeg lub cev. Yog li ntawd, nyob rau hauv cov xwm txheej uas qhov kev pheej hmoo ntawm cov khoom no tsis yog qhov tseeb, cov kws kho mob tau ceev faj ntau dua rau kev siv nws, thiab nws tseem txwv tsis pub cov poj niam cev xeeb tub siv nws.

2. Paxlovid

Paxlovid yog qhov ua ke ntawm ob yam khoom (Paxlovid / Ritonavir). Paxlovid inhibits tus kab mob replication los ntawm inhibiting cov kev ua ntawm ib tug protease, tab sis Paxlovid yog yooj yim metabolized los ntawm P450 enzyme, yog li Ritonavir yuav tsum tau siv los inhibit qhov kev ua ntawm P450 enzyme kom tswj cov concentration ntawm Paxlovid nyob rau hauv cov ntshav. Muaj ntau qhov txwv tsis pub siv Paxlovid, vim tias muaj ntau yam nyob ntawm P450 enzyme metabolism, yog li thaum siv Paxlovid, peb yuav tsum tsis txhob siv cov khoom no lossis nrhiav cov khoom siv hloov pauv, thiab cov neeg muaj lub siab tsis zoo thiab lub raum ua haujlwm tau zoo dua tsis siv lawv. Txawm li cas los xij, Paxlovid muaj cov ntaub ntawv zoo tshaj plaws hauv kev sim tshuaj, uas tuaj yeem txo tus mob hnyav thiab kev tuag ntawm 90%, yog li nws yog thawj qhov kev xaiv los kho COVID-19.

3. Remdesivir

Yooj yim muab tso, Remdesivir yuav hloov mus rau GS-441524 tom qab nkag mus rau tib neeg lub cev, zais cov nucleotide, thiab sib tw nrog lwm cov nucleotides los koom nrog cov kab mob sib kis. Thaum GS-441524 molecule tau muab tso rau hauv cov khoom lag luam luam tawm, cov ntawv luam tawm yuav raug txiav tawm ntxov, yog li inhibiting cov txheej txheem hloov pauv ntawm tus kab mob RNA. Txawm li cas los xij, cov ntaub ntawv ntawm Remdesivir hauv kev sim tshuaj tsis zoo, thiab nws muaj kev cuam tshuam me ntsis ntawm qhov hnyav thiab kev tuag, tab sis nws yuav ua rau cov kab mob luv luv thiab zoo dua sai dua.

Ntau tus tswv miv yuav tsum paub txog Remdesivir. Cov tshuaj cawm neeg txoj sia nto moo GS-441524, uas tseem yog tus kabmob coronavirus, yog cov tshuaj kho dua tshiab tom qab phosphorylation.

Raws li cov kws tshuaj ntawm peb cov khoom lag luam saum toj no, nws tuaj yeem pom tau tias cov ntsiab lus ntawm Remdesivir thiab Molupiravir zoo ib yam, ob qho tib si cuam tshuam nrog cov kab mob sib kis. Hauv txoj kev xav, Molupiravir yuav tsum tau siv los kho cov kab mob hauv plab, thiab cov nyhuv yuav tsum zoo dua. Yog li ntawd, qee cov neeg txawv teb chaws yeej sim siv Molupiravir los kho miv mob plab. Raws li tsab xov xwm los ntawm FIP Warriors, lawv tau txais cov ntaub ntawv los ntawm Molupiravir cov chaw tsim khoom, uas suav nrog 286 tus neeg mob kis kabmob kis kabmob kis thoob ntiaj teb, ntawm 28 tus neeg tau kho tom qab siv Molupiravir rau rau lub lis piam, 258 tus neeg mob tau kho tom qab siv. Molupiravir rau yim lub lis piam, tsis muaj leej twg tuag, thiab tsis muaj rov tshwm sim tom qab 3-5 hli.