Khoom physicochemical zog thiab molecular qauv ntaub ntawv
Cov ntaub ntawv yooj yim
Suav lub npe: Sildenafil
Lub npe Askiv: sildenafil
Lus Askiv alias: SIDANAFIL; Sildenafil; viagTa; Revatio;
CAS Nr .: 139755-83-2
Cov mis mos molecular: C22H30N6O4S
Tus qauv qauv:
Molecular Luj: 474.57600
Qhov tseeb: 474.20500
PSA: 121.80000
PIB: 2.56750
Lub cev thiab tshuaj muaj zog
Cov tsos mob thiab yam ntxwv: Dawb crystalline hmoov
Qhov ceev: 1.39g / cm3
Melting point: 187-189 ° C
Kub taw tes: 672.4 ºC ntawm 760 mmHg
Flash point: 360.5 ºC
Refractive Index: 1.664
Cia tej yam kev mob: Khaws nyob rau hauv thawj lub thawv nyob rau hauv ib tug txias qhov chaw tsaus
Chav siab: 6.1E-18mmHg ntawm 25 ° C
Cov ntaub ntawv kev nyab xeeb
Kev lis kev cai code: 2933990090
Hazard qeb code: R36/37/38
Cov lus qhia kev nyab xeeb: S22; S24/25; S36; S26
Cov khoom lag luam phom sij: Xi [1]
Cov ntaub ntawv molecular
1. Molar refractive index: 126.02
2. Molar ntim (cm/mol): 339.4
3. Tos Zhang Biarong (90.2K): 922.1
4. Nto nro (dyne/cm): 54.4
5. Polarization tus nqi (10-24cm3): 49.96
Xam cov ntaub ntawv tshuaj
1. Tus nqi siv rau hydrophobic parameter xam (XlogP): 1.5
2. Tus naj npawb ntawm cov nyiaj pub dawb hydrogen: 1
3. Tus naj npawb ntawm hydrogen daim ntawv lees txais: 7
4. Number of rotatable chemical bonds: 7
5. Tus naj npawb ntawm tautomers: 3
6. Topological molecular polarity nto thaj tsam 118
7. Tus naj npawb ntawm cov atom hnyav: 33
8. Nto nqi: 0
9. :838
10. Tus naj npawb ntawm isotopic atoms: 0
11. Txiav txim seb tus naj npawb ntawm atomic stereocenters: 0
12. Tsis paub tseeb tus naj npawb ntawm atomic stereocenters: 0
13. Txiav txim seb tus naj npawb ntawm cov tshuaj stereocenters: 0
14. Tus naj npawb ntawm cov tshuaj tsis paub tseeb stereocenters: 0
15. Number of covalent bond units: 1
Taw qhia rau kev sib txuas ntawm sildenafil raw cov ntaub ntawv
3-Propylpyrazole-5-carboxylic acid ethyl ester thiab dimethyl sulfate tau sib xyaw thiab ua rau kom tau 2-methyl-3-n-propylpyrazole-5{{licester. Muab nws tso rau hauv sodium hydroxide tov thiab hydrolyze nws kom tau 2-methyl-3-n-propylpyrazole-5-carboxylic acid. Ntxiv cov khoom siv hydrolysis hauv cov khoom siv rau cov kua qaub sib xyaw thiab nitration kom tau 1-methyl-4-nitro-3-n-propylpyrazole-5-carboxylic acid. Cov khoom lag luam nitration yog chlorinated nrog sulfonyl chloride los tsim acyl chloride, thiab tom qab ntawd ammonia nrog cov dej ntshiab ammonia kom tau 1-methyl-4-nitro-3-n-propylpyrazole-5-carboxamide. Cov carboxamide thiab tin dichloride dihydrate raug tshem tawm hauv ethanol thiab refluxed kom txo tau 4-amino-1-methyl-3-n-propylpyrazole-5-carboxamide. Dissolve cov khoom txo, 4-dimethylaminopyridine, thiab triethylamine hauv dichloromethane, thiab tom qab ntawd ntxiv cov tshuaj 2-ethylbenzoyl chloride hauv dichloromethane rau acylate kom tau 4- (2-ethylbenzoyl amino) -1-methyl-3-n-propylpyrazole-5-carboxamide. Cov khoom acylation tau cyclized nyob rau hauv qhov kev txiav txim ntawm sodium hydroxide tov thiab hydrogen peroxide kom tau 5- (2-ethoxyphenyl) -1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4,3d] pyridin-7-one. Ntxiv cov khoom lag luam cyclic hauv batch rau chlorosulfonic acid kom tau 5- (5-chlorosulfonyl-2-ethoxyphenyl) -1-methyl-3-n-propyl-1,6-dihydro-7H-pyrazolo [4,3d] pyridin-7-one. Tshem tawm cov khoom chlorosulfonation hauv ethanol, ntxiv 4-methylpiperazine, thiab do kom tau sildenafil.
Lub hom phiaj
Raws li ib qho kev xaiv inhibitor ntawm phosphodiesterase (PDE) V, nws tuaj yeem txhim kho cov lus teb physiological ntawm penile erection induced los ntawm TSIS tso rau hauv kev sib deev stimulation. Feem ntau yog siv rau erectile kawg ntawm noov.
Cov khoom lag luam pharmacokinetics
Sildenafil tau nqus sai sai tom qab kev tswj hwm qhov ncauj, noj cov txiaj ntsig hauv 10-40 feeb, nrog rau qhov bioavailability ntawm kwv yees li 40%. Cov tshuaj ntshav siab tshaj plaws (cmax) tau mus txog tom qab kev tswj hwm qhov ncauj ntawm lub plab khoob rau 30-120 feeb, thiab tom qab noj qhov ncauj tom qab noj mov rau 90-180 feeb. Cov neeg ua haujlwm pab dawb noj qab haus huv noj ib koob tshuaj ntawm 100mg, thiab tom qab 24 teev, cov tshuaj ntshav siab yog kwv yees li 2ng / ml, nrog rau cmax ntawm 440ng / ml. Lub siab ua haujlwm tsis zoo, lub raum tsis txaus, lossis nce qhov chaw nyob rau hauv qhov nkhaus (AUC) tom qab noj tshuaj rau cov neeg laus hnub nyoog 65 xyoos thiab siab dua. Sildenafil thiab nws cov loj circulating metabolites (N-demethylates) khi kwv yees li 96% rau plasma proteins, thiab cov protein binding tus nqi yog ywj siab ntawm tag nrho cov tshuaj concentration. Cov ntaub so ntswg tau muab faib zoo nrog lub ntim ntim (Vd) ntawm 105L. Sildenafil feem ntau yog tshem tawm los ntawm lub siab lub microsomal enzymes cytochrome P450 3A4 (CYP 3A4, thawj txoj hauv kev) thiab cytochrome P450 2C9 (CYP 2C9, theem nrab txoj hauv kev). Nws lub ntsiab metabolite (N-demethylate) muaj qhov zoo sib xws ntawm PDE xaiv rau sildenafil, nrog rau cov ntshav siab txog li 40% ntawm sildenafil. Yog li, kwv yees li 20% ntawm cov tshuaj pharmacological ntawm sildenafil los ntawm nws cov metabolites. Kev tshem tawm ib nrab ntawm lub neej ntawm sildenafil thiab nws cov metabolites yog kwv yees li 4 teev . 80% ntawm cov tshuaj noj yog tsuas yog tawm hauv daim ntawv ntawm metabolites los ntawm quav, thiab 13% yog tawm los ntawm ob lub raum . 90 feeb tom qab noj cov tshuaj, tus nqi ntawm cov tshuaj sildenafil tsawg dua 0% cov neeg noj qab haus huv tau ntsuas 0. koob.
Pharmacological teebmeem ntawm cov khoom
Sildenafil yog ib qho kev xaiv inhibitor ntawm cyclic guanosine monophosphate (cGMP) - tshwj xeeb hom 5 phosphodiesterase (PDE5) thiab yog ib qho tshuaj rau qhov ncauj siv los kho ED. Lub physiological mechanism ntawm ib txwm penile erection yuav tso tawm nitric oxide (NO) nyob rau hauv lub cev thaum lub sij hawm kev sib deev stimulation. Nitric oxide activates guanylate cyclase nyob rau hauv cov nqaij mos hlwb ntawm lub corpus cavernosum ntawm noov, ua rau ib tug nce nyob rau hauv cGMP theem, ua rau cov nqaij ntshiv nyob rau hauv lub corpus cavernosum kom so, lub cavernous sinus kom dilate, thiab cov ntshav ntws mus rau hauv, ua rau noov erection. Cov neeg mob uas muaj erectile kawg yog tshwm sim los ntawm cov nqaij ntshiv ntawm cov nqaij ntshiv nyob rau hauv lub corpus cavernosum ntawm noov. Sildenafil tsis muaj kev cuam tshuam ncaj qha rau tib neeg daim txhuam cev, tab sis tuaj yeem txhim kho cov txiaj ntsig ntawm nitric oxide los ntawm inhibiting kev tawg ntawm cGMP los ntawm PDE5 hauv daim txhuam cev. Thaum kev sib deev stimulation ua rau hauv zos tso tawm ntawm nitric oxide, sildenafil inhibits PDE5, nce cGMP qib hauv daim txhuam cev, so cov nqaij mos ntawm daim txhuam cev, thiab cov ntshav ntws mus rau hauv daim txhuam cev. Cov kev tshawb fawb tau pom tias cov lus teb erectile nce nrog cov koob tshuaj thiab cov ntshav plasma, thiab qhov ua tau zoo tuaj yeem kav ntev li 4 teev (tab sis tsis muaj zog dua li ntawm 2 teev). Kev sim hauv vitro tau pom tias sildenafil muaj kev xaiv siab rau PDE5, uas yog ntau dua 80 npaug ntawm PDE1, ntau dua 700 npaug ntawm PDE2 thiab PDE4, thiab 4000 npaug ntawm PDE3. Vim muaj kev sib raug zoo ntawm PDE3 thiab kev tswj ntawm myocardial contractility, thiab tsis muaj PDE5 nyob rau hauv myocardium, sildenafil tsis muaj qhov zoo inotropic nyhuv thiab tsis ncaj qha cuam tshuam rau myocardial contractility. Txawm li cas los xij, sildenafil tuaj yeem ua rau vasodilation ntawm cov hlab ntsha. Thaum noj qhov ncauj ntawm qhov koob tshuaj siab (100mg), nws tuaj yeem ua rau txo qis hauv supine ntshav siab [nrog qhov nruab nrab qhov siab tshaj plaws ntawm 1.12/0.73kPa (8.4/5.5mmHg)], thiab qhov txo qis hauv ntshav siab tshaj plaws tshwm sim 1-2 teev tom qab noj tshuaj. Yog li ntawd, kev ua plees ua yi tuaj yeem ua rau mob plawv thaum lub sijhawm ntshav siab tshaj plaws. Kev xaiv cov nyhuv ntawm sildenafil ntawm PDE5 tsuas yog 10 npaug ntawm PDE6, uas yog ib qho enzyme tam sim no nyob rau hauv lub retina. Yog li, sildenafil tuaj yeem ua rau pom xim txawv txav ntawm cov koob tshuaj ntau lossis cov tshuaj ntshav ntau. Ntxiv nrog rau cov nqaij leeg ntawm tib neeg corpus cavernosum, tsis tshua muaj siab ntawm PDE5 kuj tau pom nyob rau hauv platelets, hlab ntsha, visceral du nqaij, thiab pob txha pob txha. Sildenafil tuaj yeem txhim kho antiplatelet aggregation (hauv kev sim vitro), inhibit platelet thrombus tsim (hauv vivo kev sim), thiab nthuav cov hlab ntsha peripheral (hauv vivo thwmsim) los ntawm inhibiting PDE5 hauv cov ntaub so ntswg.
Cim npe nrov: sildenafil raw khoom dawb puag cas: 139755-83-2, Tuam Tshoj sildenafil raw khoom dawb puag cas: 139755-83-2 manufacturers, lwm tus neeg, Hoobkas
