Shaanxi BLOOM Tech Co., Ltd. yog ib tug ntawm cov uas paub txog manufacturers thiab lwm tus neeg ntawm raloxifene hmoov cas 84449-90-1 nyob rau hauv Suav teb. Txais tos rau cov lag luam wholesale bulk zoo raloxifene hmoov cas 84449-90-1 muag ntawm no los ntawm peb lub hoobkas. Kev pabcuam zoo thiab tus nqi tsim nyog muaj.
Raloxifene hmoov,Raloxifen, tshuaj formula C28H27NO4S, CAS 84449-90{15}}1, molecular hnyav 473.6 g/mole. Cov qauv molecular muaj lub nplhaib benzothiophene thiab ib lub nplhaib benzene, uas txuas nrog ua ke los ntawm pawg ketone. Ib tug dawb mus rau lub teeb daj crystalline hmoov. Nws yuav luag insoluble hauv dej, tab sis soluble hauv cov kuab tshuaj organic xws li ethanol, dichloromethane, thiab ethyl acetate. Nws solubility hauv dej yog qhov tsawg, kwv yees li 0.0002 mg / mL. Txawm li cas los xij, nws cov solubility yog siab hauv cov kuab tshuaj organic, xws li hauv ethanol, uas tuaj yeem ncav cuag 0.8 mg / mL. Nws muaj cov roj solubility nruab nrab thiab n-hexane / dej faib coefficient (logP tus nqi) ntawm kwv yees li 3.3. Cov qauv siv lead ua tau raug txiav txim siab los ntawm X-ray diffraction technology. Raws li cov ntaub ntawv muaj feem xyuam, cov khoom siv lead ua ntawm Raloxifen belongs rau monoclinic system thiab muaj cov txheej txheem tshwj xeeb thiab spatial pawg. Nws yog ib qho tshuaj uas muaj cov tshuaj estrogen receptor modulator (SERM) cov teebmeem. Feem ntau yog siv nyob rau hauv kev kho mob ntawm postmenopausal osteoporosis nyob rau hauv cov poj niam.
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Tshuaj Formula |
C28H27NO4S |
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Exact Mass |
473 |
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Molecular Luj |
473 |
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m/z |
473 (100.0%), 474 (30.3%), 475 (4.5%), 475 (2.7%), 475 (1.7%), 476 (1.4%) |
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Elemental Analysis |
C, 71.01; H, 5.75; N, 2.96; O, 13.51; S, 6.77 |
Melting point 250-253℃C, Boiling point 728.2 ± 60.0℃C (predicted), ceev 1.289 ± 0.06 g / cm3 (predicted), Cia txias desicate ntawm + 4℃C, Solubility DMSO: 28 mg / ml, soluble ± 8.1 (Acidity) (predicted), Daim ntawv khoom, Xim lub teeb daj
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Raloxifene, raws li kev xaiv tshuaj estrogen receptor modulator (SERM), tau dhau los ua cov tshuaj tseem ceeb rau kev kho mob pob txha hauv cov poj niam tom qab yug me nyuam txij li thaum nws pib thaum xyoo 1990. Nws ua kom muaj kev tswj hwm ob qho tib si hauv lub hom phiaj hauv nruab nrog cev xws li pob txha, hlab plawv, lub mis, thiab lub tsev menyuam los ntawm cov ntaub so ntswg- cov txheej txheem tshwj xeeb, khaws cov pob txha tiv thaiv cov tshuaj estrogen thaum tsis txhob muaj kev pheej hmoo ntawm kev loj hlob.
Cov ntsiab lus tseem ceeb ntawm raloxifene yog los tiv thaiv thiab kho cov pob txha pob txha hauv cov poj niam tom qab yug me nyuam, tshwj xeeb tshaj yog rau cov neeg muaj kev pheej hmoo ntawm pob txha. Kev tshawb fawb thoob ntiaj teb multicenter tau pom tias qhov koob tshuaj txhua hnub ntawm 60mg tuaj yeem txo qhov tshwm sim ntawm pob txha pob txha los ntawm 30% -50%, tab sis kev tiv thaiv kev tiv thaiv ntawm pob txha pob txha tseem tsis tau meej. Nws mechanism ntawm kev txiav txim yog ua tiav los ntawm inhibiting pob txha resorption:
Kev tswj cov pob txha metabolism: Raloxifene khi rau cov tshuaj estrogen receptors nyob rau saum npoo ntawm cov pob txha pob txha, ua kom osteoblast kev ua si thaum inhibiting osteoclast sib txawv, ua rau txo qis hauv cov pob txha hloov pauv cov cim (xws li - CTX) qib mus rau premenopausal ntau yam.
Kev txhim kho pob txha pob txha: Tom qab 2 xyoos ntawm kev kho mob, qhov nruab nrab ntawm cov pob txha ntom ntawm lub lumbar qaum tau nce los ntawm 2.6%, thiab lub duav pob txha ceev nce 1.6%, uas yog piv rau cov nyhuv ntawm bisphosphonates.
Fracture risk stratification: Rau cov neeg mob uas muaj FRAX cov qhab nia Ntau dua lossis sib npaug li 3% lossis keeb kwm ntawm pob txha pob txha, raloxifene tuaj yeem txo qhov kev pheej hmoo ntawm cov pob txha rov qab, tab sis nws yuav tsum tau ua ke nrog cov tshuaj calcium (1000-1200mg ib hnub) thiab vitamin D (800IU ib hnub twg).
Raloxifene hmoovnthuav tawm excitatory lossis antagonistic cuam tshuam nyob rau hauv cov ntaub so ntswg sib txawv los ntawm kev khi rau cov tshuaj estrogen receptor (ER) alpha thiab beta subtypes, tsim tshwj xeeb pharmacological nta:
Skeletal system: Nws nthuav tawm cov teebmeem estrogenic muaj zog hauv cov pob txha, ua kom txoj hauv kev ER, txhawb kev tsim cov pob txha, thiab inhibiting pob txha resorption. Cov kev sim tsiaj tau pom tias nws cov pob txha tiv thaiv yog 60% muaj zog dua li estrogen, tab sis tsis muaj kev pheej hmoo ntawm uterine hyperplasia.
Cov kab mob plawv: Los ntawm ER - kho cov lipid metabolism hauv kev tswj hwm, nws txo qis tag nrho cov roj (TC) los ntawm 5% -10% thiab qis-cov roj lipoprotein ceev (LDL-C) los ntawm 10% -15%, thaum tsis hloov cov roj lipoprotein ntau (HDL) thiab cov roj (cholesterol) siab ({10}) qib triglycerides. Qhov loj-scale randomized tswj mus sib hais (Ntxiv cov kev tshawb fawb) tau lees paub tias nws tuaj yeem txo qhov kev pheej hmoo ntawm kab mob plawv los ntawm 35%.
Lub mis thiab lub tsev menyuam: nyob rau hauv cov ntaub so ntswg ntawm lub mis, nws qhia tau hais tias ER antagonism, inhibits estrogen induced cell proliferation, thiab txo qhov kev pheej hmoo ntawm mob cancer ntawm lub mis los ntawm 76%. Tsis muaj qhov cuam tshuam rau endometrium, thiab tsis muaj qhov hloov pauv tseem ceeb hauv endometrial thickness ua ntej thiab tom qab kev kho mob, zam qhov kev pheej hmoo los ntshav ntawm cov tshuaj hormone hloov kho (HRT).
Kev pheej hmoo ntawm venous thrombosis: Nws yog ib qho tseem ceeb kom paub tias qhov kev pheej hmoo ntawm cov hlab ntsha sib sib zog nqus (DVT) thiab pulmonary embolism (PE) nce 2-3 zaug, tshwj xeeb tshaj yog thaum thawj 4 lub hlis ntawm kev kho mob thaum muaj kev pheej hmoo siab tshaj. Nws raug pom zoo kom tsis txhob siv rau cov neeg mob uas muaj keeb kwm ntawm venous thromboembolism (VTE), immobilization txheej xwm, lossis hypercoagulability.
Kev tshawb fawb ntxiv (Ntau qhov txiaj ntsig ntawm Kev Ntsuam Xyuas Mob cancer mis): 7705 cov poj niam postmenopausal tau suav nrog. Kev ua raws li 4 xyoos tau pom tias qhov kev pheej hmoo ntawm pob txha pob txha hauv pawg raloxifene raug txo los ntawm 30%, qhov kev pheej hmoo ntawm mob qog noj ntshav tau txo los ntawm 76%, thiab kev pheej hmoo ntawm mob qog noj ntshav endometrial tsis nce. Tab sis qhov tshwm sim ntawm kub flashes nce 10% piv rau cov pab pawg placebo.
Txoj kev tshawb fawb CORE (Txuas Ntxiv Cov txiaj ntsig cuam tshuam rau Evista): Txuas ntxiv ua raws- txog li 8 xyoo tau lees paub tias muaj kev tiv thaiv kev tiv thaiv ntawm raloxifene ntawm cov pob txha uas tsis yog vertebral thiab txo qis 35% ntawm kev pheej hmoo mob plawv.
Cov ntaub ntawv hauv ntiaj teb tiag tiag: Kev tshuaj xyuas ntawm US cov ntaub ntawv kho mob qhia tau hais tias kev kho mob ua raws li raloxifene yog 68%, siab dua li ntawm bisphosphonates (52%), feem ntau yog vim yog kev tswj hwm ib zaug ib hnub thiab tsawg dua kev mob plab hnyuv. Txawm li cas los xij, nws yuav tsum tau muab sau tseg tias nws cov tshuaj tiv thaiv pob txha tsis muaj zog dua li ntawm denosumab hauv cov neeg mob uas muaj pob txha loj (T tus nqi tsawg dua lossis sib npaug ntawm -3.5).
Qhov no yog peb cov khoom siab heevraloxifene hmoov
Lus Cim: BLOOM TECH (Txij li xyoo 2008), ACHIEVE CHEM-TECH yog lub chaw pabcuam ntawm peb.
Raloxifen yog ib qho tshuaj tiv thaiv estrogen uas tuaj yeem ua ke los ntawm reacting Raloxifen hydrochloride nrog rau lwm cov tshuaj reagents. Cov hauv qab no yog cov txheej txheem synthesis ntawm raloxifene thiab nws qhov sib npaug ntawm cov tshuaj:
1) React para bromobenzoic acid nrog ethyl acrylate nyob rau hauv alkaline tej yam kev mob los tsim ethyl propylene para bromobenzoic acid ester.
C6H5CH2COV + CH2=CHCOOC2H5 → C6H5CH2COOB2COJ (CH3)C2H5
2) Cov tshuaj tiv thaiv ntawm ethylpropenyl p-bromobenzoate nrog hydrocyanic acid tsim cov nitrile sib txuas.
C6H5CH2COOB2CH (CH3)C2H5+HCN → C6H5CH2C(CN)(COOS2CH (CH3)C2H5)
3) React nitrile compounds nrog dej thiab sulfuric acid los tsim cov amino acids.
C6H5CH2C(CN)(COOS2CH (CH3)C2H5) +2H2O+H2YOG4 → C6H5CH2CH (NH2)COH + CO2+ (CH3)2CHOH
4) Thaum kawg, cov amino acids reacted nrog hydrochloric acid los tsim raloxifene hydrochloride.
C6H5CH2CH (NH2)COOH+HCl → C6H5CH2CH (NH3) COJ
Raloxifene synthesis txoj kev ntawm raloxifen:
(1)
2-(4-hydroxyphenyl) benzo [b] thiophene-6-ol yog esterified los ntawm methylsulfonyl chloride, thiab qhov tshwm sim diester reacted nrog 4-(2-piperidinylethoxy) benzoyl chloride kom tau raloxifen los ntawm hydrolysis.
(2)
Siv 3-methoxyphenylthiophenol thiab 4-methoxy- -bromoacetophenone ua cov khoom pib, 6-methoxy-2-(4-acetyloxyphenyl) benzo [b] thiophene tau txais los ntawm kev hloov cov tshuaj tiv thaiv thiab cyclization cov tshuaj tiv thaiv.
(3)
Friedel-Cov tshuaj tiv thaiv khoom siv tes ua tau ua nrog 4-[2-(1-piperidinyl)ethoxy] benzoyl chloride, ua raws li cov tshuaj tiv thaiv demethylation.
(4)
Cov khoom lag luam tau txais los ntawm kev tsim cov tshuaj ntsev hauv tsib kauj ruam tseem ceeb.
(5)
Cov txiaj ntsig: Cov qauv ntawm lub hom phiaj sib xyaw tau lees paub los ntawm IR, 1H NMR thiab MS.
Xaus: Txoj kev no muaj cov tshuaj tiv thaiv me me, kev ua haujlwm yooj yim, thiab txhim kho cov txiaj ntsig. Raloxifene yog benzothiophene xaiv estrogen receptor modulator (SERM), uas muaj cov tshuaj estrogen agonistic cuam tshuam rau cov pob txha thiab cov ntshav lipids, thiab muaj cov tshuaj estrogen antagonistic cuam tshuam rau lub mis thiab lub tsev menyuam. Raloxifene yog siv rau hauv kev tshawb fawb mob qog noj ntshav thiab osteoporosis.
Raloxifen hmoovyog ib qho tshuaj estrogen receptor modulator (SERM) feem ntau siv rau kev tiv thaiv thiab kho pob txha. Cov hauv qab no yog kev tshawb fawb thiab kev loj hlob keeb kwm ntawm Raloxifen:
Kev tshawb fawb thaum ntxov:
Raloxifen txoj kev tshawb fawb tau pib ua los ntawm Eli Lilly thiab Tuam Txhab hauv Tebchaws Meskas. Lawv vam tias yuav tsim cov tshuaj uas tuaj yeem hloov kho cov tshuaj estrogen ib txwm muaj, muab cov txiaj ntsig ntawm cov pob txha muaj zog ntxiv thaum txo cov kev tsis zoo ntawm lub mis thiab lub tsev menyuam.
Kev sim tshuaj:
Hauv kev sim tshuaj thaum ntxov, cov kws tshawb fawb pom tias Raloxifene muaj cov txiaj ntsig ntawm kev tiv thaiv cov pob txha thiab tuaj yeem txo qhov kev pheej hmoo ntawm mob qog noj ntshav. Tsis tas li ntawd, piv rau cov tshuaj estrogen therapy, Raloxifene kuj pom muaj kev phiv tsawg dua, xws li lub mis hyperplasia thiab endometrial hyperplasia.
Kev pom zoo rau npe:
Raws li kev sim tshuaj ntsuam xyuas, Raloxifene tau txais kev pom zoo los ntawm US Food and Drug Administration (FDA) hauv xyoo 1997 rau kev tiv thaiv thiab kho pob txha. Nws kuj tau txais kev pom zoo los ntawm lwm lub teb chaws thiab cheeb tsam raws li ib qho tseem ceeb kho tshuaj.
Kev tshawb fawb ntxiv:
Nyob rau tib lub sijhawm, kev tshawb fawb tsom mus rau Raloxifen tau nthuav dav ntxiv, tshawb nrhiav nws cov peev txheej hauv lwm qhov chaw. Piv txwv li, cov kws tshawb fawb tau pom tias Raloxifene kuj muaj qee yam kev cuam tshuam hauv kev kho mob qog noj ntshav mis, thiab tab tom tshawb fawb txog nws kev siv ua ke nrog lwm cov tshuaj.
Zuag qhia tag nrho, kev tshawb fawb thiab kev txhim kho keeb kwm ntawmraloxifene hmoovtau dhau los ntawm cov txheej txheem los ntawm kev sim ua ntej mus rau kev pom zoo rau kev lag luam tawm. Raws li SERM, nws ua lub luag haujlwm tseem ceeb hauv kev kho mob pob txha thiab txuas ntxiv mus tshawb nrhiav thiab siv hauv kev tshawb fawb txog lwm yam kab mob. Nyob rau hauv tus txheej txheem ntawm kev tshawb fawb thiab kev loj hlob keeb kwm no, kev nyab xeeb thiab zoo dua lwm txoj kev kho mob tau coj, muab kev pab ntau dua rau cov neeg mob.
Cov lus nug nquag
Puas yog "tus neeg ua yeeb yam" lossis "cov neeg tuaj saib" hauv cov pob txha pob txha? Vim li cas nws txawv kiag li ntawm ibuprofen?
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Hauv cov pob txha pob txha, nws yog qhov tseeb 'cov neeg tuaj saib' es tsis yog 'tus neeg ua yeeb yam'. Tom qab khi rau cov tshuaj estrogen receptors, nws tsis qhib lub classical estrogen teb lub caij (ERE), tab sis es tsis txhob cuam tshuam cov kev ua ntawm lwm yam agonists xws li estradiol. Qhov no txawv kiag li ntawm Idoxifene, uas yog ib tug muaj zog agonist ntawm ERE nyob rau hauv cov pob txha hlwb. Txawm hais tias ob qho tib si yog SERMs uas thaum kawg tiv thaiv cov pob txha, lawv cov kev ua tau zoo sib txawv heev.
Dab tsi yog nws cov hmoov ntshai? Cov xwm txheej khaws cia hnyav npaum li cas?
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It's actually quite sturdy. The raw material powder can be stored in the dark at -20 ° C during drying, and its stability can last up to 3 years. Once prepared into a solution, it must be stored at -20 ° C and used within one month. Repeated freeze-thaw cycles can lead to a decrease in potency. It is almost insoluble in water, but has excellent solubility in DMSO (>90 mg / mL), ua rau nws yog ib qho hnyav hnyav rau hauv vitro thwmsim.
Yuav ua li cas ua tau "selectivity"? Qhov twg yog ob tus yuam sij tso siab rau?
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Nws tso siab rau qhov hloov ntawm AF-1 thiab AF-2 domains. Hauv lub mis thiab uterine hlwb, nws khi rau receptors thiab thaiv cov haujlwm tseem ceeb AF-2, ua rau cov noob hloov mus rau 'silence'; Hauv cov pob txha pob txha thiab daim siab, nws tso cai rau AF-1 kom qhib tau, ua kom muaj kev qhia ntawm qee cov noob muaj txiaj ntsig. Cov kev hloov pauv uas lub koom haum no tso siab rau yog lub hauv paus molecular rau nws cov kev xaiv.
Tshaj li 90% ntawm nws nyob hauv cov hlab ntsha, leej twg yog tus zoo tshaj 'tus khub mus ncig'?
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Nws khi rau ntau dua 95% ntawm cov ntshav plasma proteins, feem ntau yog albumin, thiab ib nrab khi rau alpha 1-acid glycoproteins. Qhov no txhais tau hais tias nws yog qhov yooj yim tsis yog 'dawb txav'. Yog li ntawd, thaum siv nrog rau cov tshuaj nrog tib lub siab ntawm cov protein losis tswvyim dabtsi (xws li warfarin thiab diazepam), nws yuav ua rau muaj kev hloov pauv hauv cov concentration dawb thiab yuav tsum tau ua tib zoo saib xyuas.
Cim npe nrov: raloxifene hmoov cas 84449-90-1, lwm tus neeg, manufacturers, hoobkas, lag luam wholesale, yuav, nqe, tej, kev muag khoom