Firocib TxhajPuas yog cov lus tsis txaus ntseeg los tiv thaiv kev siv tshuaj (NSAID) Nws cov khoom siv nquag, cov hluav taws xob, ua haujlwm raws li kev xaiv los ntawm cyclooxygenase {}} 2 (cox {}} 2) inhibitor. Los ntawm kev tsim txom cov khoom siv ntau lawm xws li prostaglandins xws li prostaglandins xws li prostaglandins xws li anti {{o {o; antipyretic teebmeem. Thaum lub sij hawm txo qis kev tiv thaiv kev pheej hmoo txaus ntshai nrog cov tsis xaiv NSAIDS 'inhibition ntawm cov plab zom mov thiab lub raum cox-1. Qhov kev txhaj tshuaj no yog feem ntau qhia rau kev tswj cov postoperative mob thiab osteoarthritis-cuam tshuam o hauv cov nees. Nws cov kev tsim tshwj xeeb ua kom muaj kev cuam tshuam sai sai thiab ntev ntev muab kev tswj hwm rau ntau dua 24 teev), muab kev tswj hwm yooj yim rau cov tsiaj loj. Hauv cov ntawv thov canine, nws tseem raug pom zoo rau kev tswj kev mob thiab mob tshwm sim los ntawm osteoarthritis. Siv yuav tsum tau saib xyuas cov tsiaj ua haujlwm nruj me ntsis Firepaib kev txhaj tshuaj sawv cev rau txoj kev nce qib tseem ceeb hauv cov kws kho tsiaj rau cov tshuaj kho mob rau kev tswj hwm qhov mob. Nws txoj kev xaiv siab thiab ncua sij hawm txhim kho ntau ntxiv rau kev noj qab haus huv thiab kev soj ntsuam ntawm tus khub thiab cov tsiaj ua tau zoo.
Piv nrog rau kev npaj rau ntawm qhov ncauj, txhaj tshuaj ntawm kev pib sai thiab siab dua cov kev tswj hwm kev mob hnyav lossis cov xwm txheej uas tsis tuaj yeem. Tsis yog rocoxib kev txhaj tshuaj sai sai refamps thiab mob los ntawm inhibiting {}} 2}}} 2 (PGE2), thaum txo cov kev pheej hmoo ntawm kev mob plab zom mov. Nws lub sij hawm ntev-ua haujlwm tuaj yeem txo cov zaus ntawm cov thawj coj ntawm kev tswj hwm ntawm kev tswj hwm thiab txhim kho kev ua raws li kev ua raws.
Peb Cov Khoom
Cov ntaub ntawv ntxiv ntawm kev sib txuas lus:
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Ketoconazole +. coa
Pharmacologism Ntsuas Thiab Lub Hom Phiaj
Xaiv Kev Txiav Kev Txiav Txim Siab ntawm Cox-2
Firocib Txhajinhibits kev hloov pauv ntawm arghaidonic acid rau PEGE2 los ntawm tshwj xeeb thaiv lub nquag ntawm cox-2 enzyme, yog li txo cov mob thiab mob kis. Nws txoj kev xaiv sib piv rau Cox-2 yog qhov siab li 380 zaug (dev tag nrho cov ntshav kuaj cov ntaub ntawv hauv cov nsaids (xws li Meloxicam nrog kev xaiv piv ntawm 16 lub sijhawm). Qhov kev xaiv siab no tau txais txiaj ntsig cov roj ntsha cox-1
Kev sib piv nrog lwm NSAIDs
Kev ruaj ntseg plab zom mov:
Anti inflammatory nyhuv: nyob rau hauv canine eplearthritis txhaj yuav txo cov kev sib koom ua kua los ntawm 60%, thaum ibuprofen tsuas yog txo nws los ntawm 35%.
Analgesic nyhuv: Kev txhaj tshuaj postative tau qhia tau tias tsis muaj kev txhaj tshuaj uas tsis muaj peev xwm ua kom lub sijhawm ntsuas kev kho kom zoo rau 12 teev, thaum Ketoprofen yog 8 teev.
Kev tswj hwm mob hauv cov dev
Cov Postoperative Analgesia: Cov koob tshuaj pom zoo yog 2mg / kg, tswj los ntawm kev txhaj tshuaj tiv thaiv kev ua kom muaj kev phom sij rau 24 teev. Haum rau kev phais mob orthopedic (xws li kev hloov kho hip), xws li phais hniav), thiab kho hniav. Cov kev tshawb fawb soj ntsuam tau pom tias cov qhab nia mob ncua rov qab los ntawm 40% ntawm 6 teev thiab 65% ntawm 12 teev.
Kev raug mob hnyav: xws li pob txha lov lossis mos mos raug mob los ntawm kev sib tsoo tsheb, ntog los ntawm qhov siab, tuaj yeem tswj xyuas thiab mob. Qhia txog kev sib xyaw nrog cov tshuaj opioid kom txo cov siv opioid los ntawm 30% -50%.
Cov xwm txheej tshwj xeeb: Rau cov dev nrog ntuav (xws li ntuav ntuav hnyav (maj nrawm) lossis cov neeg mob comatose, txhaj tshuaj yog qhov kev xaiv nkaus xwb.
Kev tshawb nrhiav cov ntawv thov miv
Txawm hais tias cov ntsiav tshuaj Fexorubicin tam sim no tsuas pom zoo siv rau hauv miv, thiab tsis tau ua npaws ntawm 0.75}}}} {} Txawm li cas los xij, vim muaj qhov siab rhiab ntawm cov miv mus rau NSAIDS thiab tsis muaj cov ntaub ntawv kev nyab xeeb ntawm cov khoom siv kev nyab xeeb, nws tseem muaj kev pheej hmoo thiab cov txiaj ntsig yuav tsum tau ua tib zoo ntsuas.
Cov yam ntxwv ntawm cov chaw ua ke
Pharpacynamics ntawm dev
Kev nqus thiab faib: Kev txhaj tshuaj tiv thaiv kev nkag siab, Fipronil tau nrawm nrawm nrawm (CMAX) ntawm 2.5 μ g / Peak lub sijhawm (TMAX) ntawm 1 teev. Qhov pom tseeb muab faib ntim (VD) yog 3L / KG, dav faib hauv kev sib koom ua kom huv si synovial kua, leeg, thiab adipose ntaub so ntswg.
Cov metabolism thiab ua kom zoo nkauj: feem ntau yog metabolized los ntawm CYP450 cov kab ke hauv daim siab, tsim direkylated thiab glucuronide metabolites, uas tau tawm los ntawm bile thiab feces. Ib nrab - lub neej (T1 / 2) yog 6-8 teev, thiab qhov kev tshem tawm (Caws) yog 0.5l / h.
Dose Hloov Kho: Cov dev nrog daim siab ua haujlwm yuav tsum tau txo cov koob tshuaj mus rau 1mg / kg, thaum dev muaj los kho cov tshuaj, tab sis ntshav muaj creatinine thiab urera nitrogen yuav tsum tau saib xyuas.
Kws kho mob ntawm cov nees
Kev nqus thiab faib khoom: Tom qab kev txhaj tshuaj tiv thaiv kev txhaj tshuaj, CMAX yog 1.8 μ GS G / ML, TMAX yog 0.5 teev, thiab VD yog 4L / kg.
Cov metabolism thiab ua kom zoo nkauj: cov kev sib tw metabols zoo ib yam li cov dev, tab sis ib nrab {} Lub neej yog txuas ntxiv rau 12 teev, uas yuav cuam tshuam nrog qis dua ntawm daim siab daim siab ua kom tuag.
Dose Hloov Kho: Cov neeg laus nees nrog cov kab mob plawv yuav tsum pib nrog cov ntshav qis (0.05mg / kg) thiab kaw ntshav siab thiab electrocardiogram.
Muab cov phiaj xwm thiab tswj hwm txoj kev npaj
Txheem - noj
Cov dev: 2mg / kg, intramuscularFirocib Txhajib zaug txhua hnub. Txog kev mob mob hnyav, nws tuaj yeem nce mus rau 3mg / kg, tab sis nplooj siab thiab raum muaj nuj nqi yuav tsum tau saib xyuas.
Nees: 0.1Mg / kg, txhaj tshuaj tag ib hnub. Txog kev sib tw nees, qhov kev sib tw kev sib tw tuaj yeem ua kom luv rau 12 teev, tab sis kev pheej hmoo yuav tsum tau ntsuas.
Cov kev tsis zoo thiab kev tiv thaiv pheej hmoo thiab tswj
Cov plab zom mov: ntuav (10% -15%), raws plab (8% -12%), tsawg%), feem ntau yog kev tshem tawm tus kheej.
Hepatotoxicity: Kev siv ntev ntev yuav ua rau nce qib ntawm Alp thiab Alp, muaj qhov tshwm sim ntawm kwv yees li 3% -5%, xav tau kev soj ntsuam li cas.
Lub raum lom zem: lub cev qhuav dej lossis hypovolemia tuaj yeem yooj yim ua rau muaj kev puas tsuaj raum, manifested li Hematuria, oliguria, lossis siab bun / cr.
Cov ntshav plab los ntawm cov ntshav: Cov quav dub thiab cov ntshav ntuav tsawg dua 1%, xav tau kev txwv tsis pub muaj tshuaj thiab endoscopic kev cuam tshuam.
Kev ua xua: pob khaus, khaus, angioedema, tsis tshua muaj tab sis feem ntau lub neej nyob hauv {}} kev hem.
Cov Txheej Txheem Cardiovascular: Tachycardia, tej zaum yuav cuam tshuam nrog cov qib prostaclin tsawg los ntawm COX-2 Inhibition.
Ua ntej tshuaj ntsuam xyuas: cais cov mob rwj, kev mob siab mob thiab mob raum, cev xeeb tub lossis paub meej tias cov tsiaj muaj mob khaub thuas.
Kev sib cuam tshuam yeeb tshuaj: Zam kev ua ke nrog glucocorticoids, lwm nsaids, thiab anticocants; Thaum siv kev sib xyaw ua ke nrog AceI, ntshav siab saib xyuas yog yuav tsum tau ua.
Kev Kho Mob Xwm Ceev: Tsum cov tshuaj kho tam sim ntawd thiab hu rau tus kws kho tsiaj thaum xws li cov zis ntshav, cov zis tsawg dua, thiab lwm yam tshwm sim.
Firocoxib, raws li ib tug xaiv siab cox - 2 inhibitor, muaj qhov tseem ceeb los tiv thaiv anti-mob thiab yog dav siv nyob rau hauv cov kws kho tsiaj. Kev tshawb fawb ntawm nws cov txheej txheem synthesis yog qhov tseem ceeb rau kev txhim kho cov tshuaj zoo thiab txo cov nqi ntau lawm.
Cov Khoom Siv Tshuaj Tsoos Ib Leeg
1.1 Synthesis txoj kev pib los ntawm Benzyl sulfide
1.1.1 Txoj Kev Txheej txheem cej luam
Txoj kev no pib nrog Benzyl sulfide raws li qhov pib cov khoom siv, bromrony, oxidation, ESERIFATION, ESERIFATION, ESERIFATION, ESERATION, thiab Cyclization. Cov kauj ruam tshwj xeeb yog raws li hauv qab no:
Friedel Crafts cov tshuaj tiv thaiv:
Ua kom cov tshuaj tiv thaiv kab ntsig ua ke los ntawm cov tshuaj tiv thaiv Friedel
Bromination tiv thaiv:
MethythioCetophenone undergoes ib qho txawv txav ntawm cov tshuaj tiv thaiv hydrobricrof thiab DMSYO, tsim 2-methyl-2-(4- methylthio) pheny) propan-1-ib.
Hydrolysis tiv thaiv:
2-bromo-2-Methyl-1- (4- (Methylthio) Phenyefs, ua 2-hydrot-1- (4- meyltio) Phenylas Propan-1-Ib.
Oxidation |
2-hydroxy-2-Methyl-1- (4- (Methylfe) Phenyes) Proxidant nyob rau hauv qhov kev txiav txim siab oxoidant (xws li mex-oxo-2-(methylsulfonyl) phenyl) propan-1-ib.
Esterification tiv thaiv:
2-oxo-2-Methyl-1- (Methylsulfonyl) PhenyylsulfaRide DMF, cov tshuaj reahly-1- (methylsulfonyl) phenylsl) -2- (2-acetoxyacetoxy) -1-commanone.
Ntiv nplhaib kaw:
2-methyl-1- [4- (methylsulfonyl) phenyl] -2- (2-acetoxyacetoxy) -1-propanone undergoes ring closing reaction under the action of DBU, generating 3-hydroxy-5,5-dimethyl-4- [4- (methylsulfonyl) phenyl] -2 (5H) - furanone.
Methylation Refaulation:
3 {- hydroxy-5,5-dimethyl-4- [MethylsulfraweL) Penanone underylrethane nyob rau hauv qhov kev txiav txim siab ntawm lub hauv paus (licloporbrombethanes nyob rau hauv qhov kev txiav txim siab ntawm lub hauv paus (licloporbrombethanes nyob rau hauv qhov kev txiav txim siab ntawm lub hauv paus (xws li nah, sodium methoxide, thiab lwm yam) los ua rocuroniu.
1.1.2 Txoj Kev Coj Zoo
Ntau cov kauj ruam:
Txoj kab kev no cuam tshuam cov kauj ruam ntau, kev ua haujlwm nyuaj, thiab siab yuav tsum muaj rau cov kev mob.
Cov Khoom Siv Raw Ua Tau Zoo:
Qee cov ntaub ntawv raw (xws li benzyl sulfide, isobutyryryrylinelchloride, thiab lwm yam) muaj cov nqi ntau lawm, uas nce ntau lawm tus nqi.
Lub siab ib puag ncig:
Qee cov reagents siv nyob rau hauv cov txheej txheem cov tshuaj tiv thaiv (xws li kua txheem bromine, chloroform, thiab lwm yam) tsis yog tus phooj ywg nyab xeeb.
1.2 Synthesis txoj kev pib los ntawm P - bromhothenylacetone
1.2.1 Txoj Kev Txheej txheem cej luam
Txoj kev no siv P - Bromophenylacetone raws li cov kauj ruam pib xws li kev pib siv methylation, kev ua haujlwm, thiab cmyas. Cov kauj ruam tshwj xeeb yog raws li hauv qab no:
Methylation Refaulation:
Pib los ntawm P - bromhotianes reascation, thiab lwm yam) poov xab ua rau meteroxide, thiab lwm yam) los tsim ua ntej theem nrab.
Sulfation |
Thawj zaug nruab nrab undergoes ib cov kev tawm tsam sulfation nrog sodium methylsulfite nyob rau hauv lub catalyylsulfite nyob rau hauv kev tsim ntawm ob nrab thib ob hauv nruab nrab.
Hydroxylation Txawv:
Lub thib ob nruab nrab underghoes hydroxylation cov tshuaj tiv thaiv nyob rau hauv lub catalysis ntawm n} promosuccinimide (nbs}
Esterification tiv thaiv:
Tsis rocuronium intermediate incledice interification cov kev tshuaj tiv thaiv nrog acetoxyacetyl chloride nyob rau hauv qhov kev txiav txim ntawm lub hauv paus (
Ntiv nplhaib kaw:
2-methyl-1- [4- (methylsulfonyl) phenyl] -2- (2-acetoxyacetoxy) -1-propanone undergoes ring closing reaction under the action of DBU, generating 3-hydroxy-5,5-dimethyl-4- [4- (methylsulfonyl) phenyl] -2 (5H) - furanone.
Methylation Refaulation:
3 {{{{}} hydroxy-5,5-dimethyl-4- [MethylsulforAl)
1.2.2 Txoj Kev Coj Ua
Cov kauj ruam yooj yim:
Piv rau txoj kev pib los ntawm Benzyl sulfide, txoj kev no ua kom yooj yim qee cov tshuaj tiv thaiv thiab txhim kho cov tshuaj tiv thaiv kev ua tau zoo.
Tus phooj ywg zoo:
Zam kev siv cov tshuaj tiv thaiv ib puag ncig tsis zoo (xws li kua tawg, chloroform, thiab lwm yam), txo ib puag ncig.
Muaj kev yooj yim ntawm cov khoom raw:
Qee cov ntaub ntawv raw (xws li p - bromhothenylacetone, sodium methylsulfite, thiab lwm yam) muaj qhov yooj yim kom tau txais.
Cov khoom lag luam
Txhim kho txoj kev synthesis
Txhim kho cov kev tshwm sim zoo
Los ntawm kev ua kom zoo tshaj plaws cov tshuaj tiv thaiv cov kev mob ib txwm muaj, cov tshuaj tiv thaiv tawm thiab cov nqi kev coj dawb huv tuaj yeem raug txo kom tsawg. Piv txwv li:
Kev xaiv catalyst ntau ntxiv: xws li catalys siv tau zoo (xws li palladium catalyststs, thiab lwm yam) tuaj yeem txhim kho cov tshuaj tiv thaiv thiab xaiv tau.
Kev xaiv cov kuab: Xaiv qhov kev daws teeb meem ntau dua (xws li polar tsis muaj cov tshuaj solubents, thiab lwm yam) thiab lwm yam.
Cov tshuaj tiv thaiv kub thiab sijhawm: Ua kom tau zoo rau cov tshuaj tiv thaiv kub thiab sijhawm tuaj yeem zam dhau qhov tshwm sim ntawm cov khoom siv sab nraud thiab txhim kho cov txiaj ntsig ntawm cov khoom lag luam.
Taw qhia txog cov kev tawm tsam tshiab tshiab
Qhia cov tshuaj tiv thaiv tshiab xws li Microwave {{} Pab hluavtaws, thiab muaj peev xwm ua rau Synthesis, thiab tuaj yeem nrawm cov tshuaj tiv thaiv kev ua haujlwm. Piv txwv li:
Microwave pab cov hluavtaws: los ntawm kev siv cov kev nrawm thiab kev sib txawv ntawm microwave cua sov, cov kev txiav txim siab tuaj yeem ua kom luv thiab cov tshuaj tiv thaiv tawm tuaj yeem hloov kho.
Ultrasonic pab cov khoom siv hluav taws xob: los ntawm kev siv cov cavitation thiab kev sib cav sib ceg ntawm cov neeg sib cav sib ceg ntawm cov kev sib cav sib ceg
Cim npe nrov: Cov Hluav Taws Xob Hluav Taws Xob, Chaw Tsim Tshuaj, Chaw Tsim Tshuaj, Hoobkas, lag luam Wholesale, Yuav, Nqe, loj, rau muag