Shaanxi BLOOM Tech Co., Ltd. yog ib qho ntawm cov tuam ntxhab thiab cov muag khoom ntawm filgotinib cas 1206161-97-8 hauv Suav teb. Txais tos rau cov lag luam wholesale bulk zoo filgotinib cas 1206161-97-8 muag ntawm no los ntawm peb lub hoobkas. Kev pabcuam zoo thiab tus nqi tsim nyog muaj.
FilgotinibCov mis mos molecular yog C21H23N6O3S, CAS 1206161-97{15}}8, thiab qhov hnyav molecular yog 441.52 g / mol. Nws yog cov hmoov dawb dawb, tsis muaj ntxhiab tsw. Soluble hauv DMSO ntawm chav tsev kub, me ntsis soluble hauv ethanol, insoluble hauv dej. Nws muaj cov thermal stability zoo thiab tuaj yeem khaws cia rau lub sijhawm ntev hauv cov xwm txheej ruaj khov. Nws yog ib qho nruab nrab ligand thiab tsis tuaj yeem koom ncaj qha rau hauv cov tshuaj tiv thaiv redox. Txawm li cas los xij, thaum complex nrog lwm cov hlau ions, redox zog tuaj yeem nthuav tawm. Hauv kev sim tshuaj, nws tau raug pov thawj tias muaj kev nyab xeeb ntawm cov tshuaj kho mob, tab sis hauv kev sim tsiaj, cov khoom siv tshuaj ntau yuav ua rau lub siab toxicity thiab kev loj hlob toxicity. Nws yog ib qho me me molecule compound rau kev kho qhov ncauj ntawm rheumatoid mob caj dab thiab lwm yam kab mob autoimmune. Txawm li cas los xij, thawj cov tshuaj uas tsim los ntawm Shaanxi Achieve chem-tech Co., Ltd tsuas yog siv nyob rau hauv lub chaw soj nstuam.
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Tshuaj Formula |
C21H23N5O3S |
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Exact Mass |
425 |
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Molecular Luj |
426 |
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m/z |
425 (100.0%), 426 (22.7%), 427 (4.5%), 427 (2.5%), 426 (1.8%), 428 (1.0%) |
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Elemental Analysis |
C, 59.28; H, 5.45; N, 16.46; O, 11.28; S, 7.53 |
Lub molecular qauv ntawm nws yog raws li nram no:
Nyob rau hauv tas li ntawd, lub nplhaib nruab nrab yog tsim los ntawm ib tug carbazole derivative thiab ib tug pyrrolopyrimidine derivative, thiab ob yog txuas los ntawm ib pawg methyl. Muaj ib qho pyridoxone oxygen atom, ib pawg alkylamino thiab ib pawg acrylamide ntawm lub heterocycle. Tag nrho cov molecule nthuav tawm cov duab sib tw helical, uas ua rau cov khoom lag luam muaj kev xaiv siab thiab kev sib raug zoo rau JAK1 txoj kev taw qhia.
Nws yog ib qho tshuaj lom neeg ruaj khov me me molecular compound uas tsis yooj yim rau decomposition tshuaj nyob rau hauv ib txwm muaj mob. Txawm li cas los xij, vim tias nws yog ib qho khoom siv electrophilic, cov tshuaj tiv thaiv ntxiv lossis cov tshuaj nucleophilic hloov pauv yuav tshwm sim hauv dej.
Tsis tas li ntawd, nws kuj tseem tuaj yeem koom nrog hauv cov tshuaj tiv thaiv amide hydrolysis, uas hydrolyzes pawg acrylamide rau hauv acrolein thiab amino compounds. Cov tshuaj tiv thaiv hydrolysis no tuaj yeem tshwm sim hauv vivo lossis hauv vitro metabolism, thiab tuaj yeem cuam tshuam rau cov tshuaj pharmacological thiab metabolic kinetics ntawm cov khoom.
Nyob rau hauv dav dav, raws li ib tug tshuaj nyob rau hauv lub qhov ncauj, nws yuav tsum tau absorbed nyob rau hauv lub digestive ib ntsuj av thiab nkag mus rau hauv cov ntshav ncig kom exert pharmacological teebmeem. Yog li ntawd, nws cov tshuaj tiv thaiv muaj qee yam cuam tshuam rau kev nqus tshuaj, metabolism thiab pharmacodynamics, uas yuav tsum tau xav txog hauv cov txheej txheem ntawm kev tsim tshuaj thiab kev npaj.
Filgotinibyog lub qhov ncauj me me molecule compound rau kev kho mob rheumatoid mob caj dab thiab lwm yam kab mob autoimmune. Nws yog Janus kinase (JAK) inhibitor uas thaiv ntau txoj hauv kev hauv lub hlwb, txo qhov mob thiab lub cev tsis muaj zog. Txhua yam kev siv khoom hauv chaw kho mob thiab ua ntej- chaw kho mob yuav raug piav qhia meej.
1. Kev kho mob rheumatoid mob caj dab:
Rheumatoid mob caj dab yog ib hom kab mob autoimmune uas cov neeg mob feem ntau ntsib cov tsos mob xws li pob qij txha thiab mob. Nws yog ib qho kev xaiv JAK1 inhibitor uas tuaj yeem txo cov tsos mob ntawm rheumatoid mob caj dab los ntawm kev hloov kho lub cev tiv thaiv kab mob. Ntau qhov kev sim tshuaj tau ua pov thawj tias nws tuaj yeem txhim kho cov tsos mob xws li kev sib koom ua haujlwm, mob thiab o hauv cov neeg mob rheumatoid mob caj dab.
2. Kev kho mob plab hnyuv kab mob:
Kab mob plab hnyuv, nrog rau Crohn's kab mob thiab cov kab mob plab hnyuv, yog ib qho mob ntev, tsis tuaj yeem mob plab hnyuv. Nws tuaj yeem txo cov kab mob plab hnyuv los ntawm inhibiting JAK1 signaling pathway, thiab xav tias yuav dhau los ua cov tshuaj tshiab rau kev kho mob plab hnyuv. Cov kev sim ua ntej kuaj pom tau hais tias nws muaj txiaj ntsig zoo hauv kev kho mob plab hnyuv.
3. Kho psoriasis:
Psoriasis yog ib hom kab mob autoimmune ntawm daim tawv nqaij uas muaj cov plaques, erythema, thiab scaling ntawm daim tawv nqaij. Nws tuaj yeem pab tswj kev ua haujlwm ntawm lub cev tiv thaiv kab mob thiab txo cov tsos mob ntawm cov neeg mob psoriasis los ntawm inhibiting JAK1 signaling pathway. Kev soj ntsuam tsis tu ncua Phase II yog ntsuas kev nyab xeeb thiab kev ua tau zoo ntawm cov khoom hauv kev kho mob psoriasis.
4. Kev kho mob ntawm cov kab mob lupus erythematosus:
Systemic lupus erythematosus yog ib hom kab mob autoimmune uas tsis paub etiology uas ua rau cov tsos mob xws li mob leeg, qaug zog thiab kub taub hau. Nws tuaj yeem txo cov lus teb inflammatory thiab kev ua haujlwm ntawm lub cev tiv thaiv kab mob hauv cov neeg mob uas muaj kab mob lupus erythematosus los ntawm inhibiting JAK1 teeb liab txoj kev, yog li txo cov tsos mob ntawm cov neeg mob. Tam sim no, nws tab tom nrhiav kev sim tshuaj ntsuam xyuas nws txoj kev nyab xeeb thiab kev ua tau zoo hauv kev kho mob lupus erythematosus.
5. Kev kho mob ntawm qhov muag qhuav:
Kab mob qhov muag qhuav yog ib yam kab mob qhov muag. Cov neeg mob yuav hnov qhov muag qhuav, stinging, qhov muag nkees thiab lwm yam tsos mob. Nws tuaj yeem txo cov tsos mob hauv cov neeg mob uas muaj kab mob qhov muag qhuav los ntawm kev txo qis cov lus teb inflammatory hauv lub cev. Ib txoj kev tshawb fawb tsis tu ncua qhia tau hais tias nws muaj peev xwm zoo rau kev kho mob ntawm qhov muag qhuav.
Zuag qhia tag nrho,Filgotinibyog ib qho dav -spectrum kho tshuaj uas tuaj yeem txo cov tsos mob cuam tshuam nrog ntau yam kab mob autoimmune los ntawm kev hloov kho cov haujlwm ntawm lub cev tiv thaiv kab mob. Nyob rau hauv lub neej yav tom ntej, nrog kev tso tawm ntau qhov kev sim tshuaj ntsuam xyuas, nws xav tias yuav dhau los ua cov tshuaj tshiab rau kev kho mob ntawm ntau yam kab mob autoimmune.
6. Core indications thiab mechanism ntawm kev txiav txim
1. Rheumatoid mob caj dab (RA)
Mechanism ntawm kev txiav txim: Fego tinib, raws li ib tug xaiv JAK1 inhibitor, lub hom phiaj lub teeb liab transduction ntawm pro-inflammatory cytokines xws li IL-6 thiab TNF - . Los ntawm inhibiting txoj kev JAK1-STAT3, txo cov theem ntawm inflammatory yam tseem ceeb nyob rau hauv synovitis, thiab slowing down tus txheej txheem ntawm kev puas tsuaj.
Kev sim tshuaj kho mob:
DARWIN series ntawm cov kev tshawb fawb: Phase III kev sim tshuaj (DARWIN 1/2/3) tau pom tias ntawm koob tshuaj 200mg QD, ACR20 teb tus nqi (20% kev txhim kho hauv cov tsos mob sib koom) mus txog 76% -80%, zoo dua li cov placebo pawg (43% -50%).
Kev ua tau zoo nyob rau lub sijhawm ntev: Txoj Kev Qhib Daim Ntawv Qhia Ntxiv (GLADIUS) tau pom tias kev kho mob tas mus li 4 xyoos txo qhov kev pheej hmoo ntawm kev sib koom ua ke ntawm kev kuaj pom (xws li pob txha yaig) los ntawm 46% thiab ua tiav qhov kev tshem tawm tsis tu ncua ntawm 60%.
Kev kho kom zoo: Piv nrog cov tshuaj hluavtaws DMARDs xws li methotrexate, fegolotinib muaj qhov pib ua haujlwm sai dua (txhim kho qhov mob hauv 2 lub lis piam) thiab tseem muaj txiaj ntsig zoo rau cov neeg mob RA refractory (cov neeg uas tsis muaj lus teb rau biologics).
2. Ulcerative colitis (UC)
Cov xwm txheej kho mob: Thawj qhov pom zoo ntawm qhov ncauj JAK inhibitor rau nruab nrab mus rau UC hnyav, sau qhov sib txawv ntawm kev kho mob rau cov neeg mob uas tsis txaus cov lus teb rau biologics xws li TNF monoclonal antibodies.
Kev sim tseem ceeb:
Kev Tshawb Fawb Kev Xaiv: Tag nrho ntawm 2040 tus neeg mob tau cuv npe, thiab qhov chaw kho mob tshem tawm tus nqi (Mayo qhab nia tsawg dua lossis sib npaug rau 2) hauv 200mg QD pab pawg tom qab 10 lub lis piam ntawm kev kho induction yog 26.1%, thaum tus nqi tso tawm tom qab 58 lub lis piam ntawm kev kho mob yog 37.2%.
Kev noj tshuaj kom zoo: Rau cov tib neeg uas hnyav dua 50kg lossis nrog lub siab nruab nrab thiab lub raum ua haujlwm tsis zoo, qhov ntau npaum li cas yuav tsum raug txo rau 100mg QD kom sib npaug ntawm kev ua tau zoo thiab kev nyab xeeb.
Cov yam ntxwv ua haujlwm: Los ntawm inhibiting JAK1-STAT1/3 txoj hauv kev, txo cov cytokines xws li IFN - thiab IL-17, txhim kho txoj hnyuv mucosal, thiab txo cov ntshav thiab raws plab.
Kev siv siab -kev ua tau zoo sib koom ua ke, CRA series tuaj yeem ua rau lub sijhawm nce los ntawm 25%, thiab cov khoom lag luam tuaj yeem ncav cuag lub ncov tshiab; kev vibration suppression algorithm tau hloov kho kom ua tiav qhov zoo los tiv thaiv - co nyhuv; tag nrho - parameter DH them nyiaj algorithm thiab TrueMotion algorithm yog kev txhawb nqa 2. 0.4 hli nyob rau hauv qhov kev hloov ntawm tus cwj pwm txav, thiab cov lus nkhaus yog qhov tseeb thiab ruaj khov.
3. Psoriatic mob caj dab (PsA)
Clinical pov thawj:
MANTA RAy txoj kev kawm: Kev kho mob nrog 200mg QD rau 13 lub lis piam ua rau cov lus teb ntawm 48% rau cov tsos mob ntawm daim tawv nqaij (PASI qhab nia qis dua lossis sib npaug li 50%) thiab 56% rau cov tsos mob sib koom (ACR20).
Mechanism of action: inhibit JAK1-STAT1/3 txoj hauv kev, txo cov cytokines xws li IL-17 thiab IL-23, thiab txhim kho cov quav hniav thiab cov kab mob sib txuas.
Kev kho kom zoo: Rau cov neeg mob PsA uas tsis txaus cov lus teb rau methotrexate, kev sib xyaw ntawm cov tshuaj tsis yog gefitinib thiab kev kho mob hauv zos tuaj yeem txhim kho lawv lub neej zoo.
Filgotinibyog lub qhov ncauj me me molecule compound rau kev kho mob rheumatoid mob caj dab thiab lwm yam kab mob autoimmune. Tag nrho cov txheej txheem hluavtaws rau cov khoom yuav raug piav qhia.
Lub synthesis ntawm nws pib nrog amination ntawm 5-fluoro-2-methylaniline. Ua ntej, hnov mob 5-fluoro-2-methylaniline nrog sodium isopropyl bisulfate los ua kom muaj qhov sib txuam amide intermediate. Tom qab ntawd, nyob rau hauv qhov kev txiav txim ntawm sodium carbonate thiab methanol, amide intermediate tau decomposed muab 5-fluoro-2-methylaniline.
Tom ntej no, muab 5-fluoro-2-methylaniline thiab cis- thiab trans-acrylonitrile ua ke nrog N, N-dimethylformamide (DMF) thiab triethylamine rau hauv cov tshuaj tiv thaiv fwj raws li, thiab siv DCC (di Carboxyl chloride chemistry) los yog DIC'excardicyclohide (N, N. cov activators. Tom qab cov tshuaj tiv thaiv, trans thiab cis-2-[(5-fluoro-2-methylphenyl)amino]-3-pyrrolidine-1-carbonitrile tau txais ua ob chiral isomers. Cov kauj ruam no kuj tseem hu ua Ugi cov tshuaj tiv thaiv.
Nyob rau hauv cov kauj ruam tom ntej, methylated tetracycline nyob rau hauv lub trans isomer yog xaiv oxidized siv ib tug xaiv catalyst nyob rau hauv lub xub ntiag ntawm formic acid thiab ethylene glycol los ua tus -CHO substituent. Tom qab ua tib zoo optimization, tau txais cov khoom lag luam siab.
Tom qab ntawd, cov trans isomer-2-[(5-fluoro-2-methylphenyl)amino]-3-(4-methoxymethylphenylthio)-pyrrolidin-1-ol tau tov nrog N- Chlorobutyldimethylcarbamate (CBDA) rau kev sib txuas sib txuas. Cov kev mob tshwm sim tau ua tiav ntawm qhov kub qis ntawm -78℃hauv qab cua nitrogen. Cov khoom kawg yog nws.
Saum toj no yog cov lus piav qhia ntxaws txog tag nrho cov txheej txheem hluavtaws ntawm cov khoom. Cov txheej txheem no tau tsim thiab ua kom zoo dua qub, lub sijhawm- siv lub chaw kuaj xyuas kom tau txais txiaj ntsig thiab cov khoom zoo huv si thiab xyuas kom cov khoom zoo raws li cov qauv kev lag luam kws tshuaj.
Kev taw qhia yav tom ntej thiab kev sib tw
● Cov Tshuaj Kho Mob Tus Kheej
Raws li peb txoj kev nkag siab ntawm pathophysiology ntawm cov kab mob autoimmune txuas ntxiv mus, muaj kev txaus siab ntxiv rau cov tshuaj kho tus kheej uas kho kho rau tus neeg mob tus yam ntxwv. Filgotinib qhov kev xaiv siab rau JAK1 ua rau nws yog tus neeg sib tw txaus nyiam rau kev kho tus kheej, vim nws tuaj yeem muab kev ua tau zoo thiab kev nyab xeeb hauv cov neeg mob tshwj xeeb. Kev tshawb fawb yav tom ntej yuav tsom rau kev txheeb xyuas biomarkers uas tuaj yeem kwv yees cov lus teb rau filgotinib thiab qhia kev txiav txim siab kho mob.
● Kev Kho Mob Ua Ke
Kev sib xyaw ua ke nrog filgotinib thiab lwm yam DMARDs lossis biologics tuaj yeem txhim kho kev ua tau zoo thiab txo qhov kev pheej hmoo ntawm cov xwm txheej tsis zoo. Cov kev sim tsis tu ncua tab tom tshawb nrhiav cov txiaj ntsig zoo ntawm kev sib txuas filgotinib nrog cov neeg ua haujlwm xws li qog necrosis factor (TNF) inhibitors, IL-17 inhibitors, thiab B-cell depleting agents. Cov kev tshawb fawb no yuav muab kev nkag siab zoo rau kev siv filgotinib hauv kev sib xyaw ua ke.
● Kev tswj hwm thiab kev ua lag luam nyuaj
Txawm hais tias nws cov ntaub ntawv kho mob tau txais txiaj ntsig, filgotinib tau ntsib cov teeb meem kev tswj hwm, tshwj xeeb hauv Tebchaws Meskas, qhov twg Lub Chaw Tswj Xyuas Khoom Noj thiab Tshuaj (FDA) tau tshaj tawm Tsab Ntawv Teb Ua tiav (CRL) xyoo 2020, hais txog kev txhawj xeeb txog qhov txiaj ntsig tag nrho- cov ntaub ntawv pheej hmoo ntawm cov tshuaj. Qhov kev txiav txim siab no tau ncua kev pom zoo ntawm filgotinib hauv Asmeskas kev lag luam, txawm hais tias nws tseem muaj nyob hauv Europe thiab Nyiv. Hais txog cov kev txhawj xeeb txog kev tswj hwm no thiab ua cov kev tshawb fawb ntxiv kom paub ntxiv txog kev nyab xeeb thiab kev ua tau zoo ntawm filgotinib yuav yog qhov tseem ceeb rau nws txoj kev pom zoo thoob ntiaj teb thiab kev lag luam ua tiav.
Cov lus nug nquag
Vim li cas nws cov metabolite nquag 10 npaug tsawg dua li cov tshuaj thawj zaug, tab sis tseem yog qhov tseem ceeb rau kev ua haujlwm hauv vivo?
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Vim tias qhov cuam tshuam ntawm cov metabolite hauv tib neeg lub cev yog 16-20 npaug siab dua li cov tshuaj qub, nws txaus los them rau nws cov txiaj ntsig tsis txaus. Qhov sib xyaw ua ke ntawm ob lub sijhawm ncua sijhawm inhibition ntawm cov tshuaj ntawm JAK1 txoj hauv kev.
Dab tsi yog qhov tshwj xeeb zoo ntawm kev pheej hmoo tshuaj yeeb tshuaj piv rau lwm yam JAK inhibitors?
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Nws tsis yog metabolized los ntawm daim siab CYP450 enzyme thiab yog substrate rau P-glycoprotein. Yog li ntawd, thaum siv ua ke nrog cov tshuaj tiv thaiv kab mob, tshuaj tua kab mob, lossis tshuaj kho mob plawv, qhov tshwm sim ntawm kev sib cuam tshuam tseem ceeb yog tsawg thiab feem ntau tsis tas yuav hloov tshuaj.
Vim li cas tus mob rheumatoid tseem tsis tau pom zoo rau kev kho mob hauv Tebchaws Meskas?
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Tsoomfwv Meskas cov cai tswjfwm tshuaj muaj kev txhawj xeeb txog qhov muaj peev xwm ua rau cov qog nqaij hlav toxicity. Qhov kev thov rau cov ntaub ntawv tshawb fawb ntau ntxiv ntawm nws qhov cuam tshuam rau cov phev tsis zoo hauv xyoo 2020 ncaj qha coj mus rau ncua sijhawm ntawm kev ntsuam xyuas ntawm nws cov kev qhia rau RA hauv Tebchaws Meskas.
Puas muaj qhov sib txawv tseem ceeb hauv kev ua tau zoo thiab kev nyab xeeb ntawm 200mg thiab 100mg koob tshuaj hauv kev kho mob rheumatoid mob caj dab?
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Hais txog kev ua tau zoo, kev tshawb fawb tau pom tias tsis muaj qhov sib txawv ntawm ob qho tib si. Tab sis qhov kev tshawb fawb txog kev nyab xeeb ntev ntev tshaj plaws qhia tau tias yuav muaj peev xwm sib cuam tshuam ntawm qhov koob tshuaj 200mg thiab muaj kev pheej hmoo ntau dua ntawm cov kab mob shingles, malignancy, thiab tag nrho - ua rau cov neeg mob tuag ntau dua 65 xyoo.
Dab tsi tshwj xeeb yuav cuam tshuam qhov kev ua tau zoo ntawm kev kho mob yav dhau los rau cov neeg mob uas muaj cov kab mob ulcerative colitis?
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Kev tshawb fawb tau pom tias cov kev kho mob siab dua (xws li biologics) uas tau siv yav dhau los, qhov ua tau zoo ntawm cov tshuaj tsis yog gefitinib yuav tsis zoo. Qhov no qhia tau hais tias nws txoj haujlwm ua ntu zus hauv txoj kev kho mob tuaj yeem cuam tshuam rau nws cov txiaj ntsig tiag tiag.
Cim npe nrov: filgotinib cas 1206161-97-8, lwm tus neeg, manufacturers, hoobkas, lag luam wholesale, yuav, nqe, tej, kev muag khoom