drug design 蒋学华、王凌 四川大学华西药学院...
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drug design 蒋学华、王凌 四川大学华西药学院 临床药学与药事管理学系. 药物设计 —— drug design. 根据药物体内过程，设计理想的药物与药物制剂的理论、技术和方法。 理想的药物 药效－药理毒理 药动－ ADME 新药研究开发 筛选 设计. 药物设计. 利用分子生物学、细胞生物学、免疫学、遗传学、生物化学、药物化学、结构化学、生物药剂学、药动学、药理学及计算机的技术与方法，交叉渗透，形成的一门新兴学科。 - PowerPoint PPT Presentation
Transcript of drug design 蒋学华、王凌 四川大学华西药学院...
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drug design
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drug design
ADME
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0.91.3
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lead compoundprototype
drug delivery system,DDS
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(Accidentally Discover)
(From Active Component Of Natural Resources)
From Immanent Active Substance
From Side-Effect Of Medicine
From Active MetabolitesBy Combinatorial Chemistry
(Rational Drug Design, RDD) Computer-aided Drug Design, CADD
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(optimization)
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target-based drug design:
structure-based drug design:
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Properties Based Drug Design, PBDDADME
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Structure-pharmacokinetics Relationship, SPRStructure-activity Relationship, SAR
Quantitative Structure-pharmacokinetics Relationship, QSPRQuantitative structure-pharmacokinetics relationship QSPR
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Absorption, ADistribution, DMetabolism, MpH Excretion, E
Transport(Elimination) Disposition)
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/ (Passive transport) (Carrier-mediated transport) (Membrane mobile transport )
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/
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TransportersMembrane Transport Proteins -ACEPepT1
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Paracellular TransportTight Junction, TJ30100nm
6080 nm2938 nm23 nm
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logD7.4pH
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rifampicinrifamycinVdClrifabutin
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710 m7 mMPS6090%2%10%3%10%50 nm
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Drug Likeness
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ADME
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LipinskiThe LipinskiRule of Five
501000logDpKa
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logPlogDlogPPlog PHanschLopPADME
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pHlogDlogDlogPpKapH
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IAMCaco-2MDCK
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PAMPAUV
5%PAMPACaco-2PAMPA
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11793242124641500110020
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>5005100
>551
>1052
logP>5(ClogP)>4.15(MlogP)(51)
90%
(Rule of Five)
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BayesianACDAvailable Chemicals Directory Database3500CMC3500CMC90%ACD10%MDDRMDL Drug Data Report80%
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metoprololCYP2D6betaxolol
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amlodipinefelodipinenifedipinenitrendipine
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Solid DispersionInclusion CompoundsMicroemulsionsEmulsionMicroparticles Microcapsules MicrospheresNanoparticles Nanospheres NanocapsulesLiposomes
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BCS
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37pH1-7.5/D:S)250ml90%FDA/Caco-290%
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Coating MaterialMembrane WallMicrocapsules/MicrospheresMicroparticles1250 mMicroencapsulation
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(Nanospheres)(Nanocapsules)(Nanoparticles)101000nm
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ADME/T
ADME/T
ADME/T
ADME/T
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1964198431950.4%ADME/T
*2002FDA10030
*R&D
*QC
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