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ID:7895500
大小:2.19 MB
页数:137页
时间:2018-03-02
《smith, d pharmacokinetics and metabolism in drug design外语英文电子书》由会员上传分享,免费在线阅读,更多相关内容在教育资源-天天文库。
1、PharmacokineticsandMetabolisminDrugDesign1EditedbyD.A.Smith,H.vandeWaterbeemd,D.K.Walker,R.Mannhold,H.Kubinyi,H.TimmermanCopyright©2001Wiley-VCHVerlagGmbHISBNs:3-527-30197-6(Hardcover);3-527-60021-3(Electronic)1PhysicochemistryAbbreviationsCPCCentrifugalp
2、artitionchromatographyCoMFAComparativefieldanalysis3D-QSARThree-dimensionalquantitativestructure–activityrelationshipsIUPACInternationalUnionofPureandAppliedChemistryMLPMolecularlipophilicitypotentialRP-HPLCReversed-phasehighperformanceliquidchromatograph
3、yPGDPPropyleneglycoldipelargonateSFShakeflask,referringtotraditionalmethodtomeasurelogPorlogDSymbols∆logDDifferencebetweenlogDinoctanol/waterandlogDinalkane/water∆logPDifferencebetweenlogPinoctanol/waterandlogPinalkane/waterfRekkerorLeo/Hanschfragmentalco
4、nstantforlogPcontributionKaIonizationconstantΛPolarityterm,mainlyrelatedtohydrogenbondingcapabilityofasolutelogPLogarithmofthepartitioncoefficient(P)ofneutralspecieslogDLogarithmofthedistributioncoefficient(D)ataselectedpH,usuallyassumedtobemeasuredinocta
5、nol/waterlogDoctLogarithmofthedistributioncoefficient(D)ataselectedpH,measuredinoctanol/waterlogDchexLogarithmofthedistributioncoefficient(D)ataselectedpH,measuredincyclohexane/waterlogD7.4Logarithmofthedistributioncoefficient(D)atpH7.4MWMolecularweightπH
6、anschconstant;contributionofasubstituenttologPpKaNegativelogarithmoftheionizationconstantKa21Physicochemistry1.1PhysicochemistryandPharmacokineticsThebodycanbeviewedasprimarilycomposedofaseriesofmembranebarriersdi-vidingaqueousfilledcompartments.Thesememb
7、ranebarriersarecomprisedprin-cipallyofthephospholipidbilayerswhichsurroundcellsandalsoformintracellularbarriersaroundtheorganellespresentincells(mitochondria,nucleus,etc.).Theseareformedwiththepolarionizedheadgroupsofthephospholipidfacingtowardstheaqueous
8、phasesandthelipidchainsprovidingahighlyhydrophobicinnercore.Tocrossthehydrophobicinnercoreamoleculemustalsobehydrophobicandabletosheditshydrationsphere.Manyoftheprocessesofdrugdispositiondependontheabilityorinabilit
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