If you can't read please download the document
Upload
nariko
View
460
Download
13
Embed Size (px)
DESCRIPTION
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
Citation preview
drug design
drug design
ADME
0.91.3
lead compoundprototype
drug delivery system,DDS
;
(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
(optimization)
target-based drug design:
structure-based drug design:
Properties Based Drug Design, PBDDADME
Structure-pharmacokinetics Relationship, SPRStructure-activity Relationship, SAR
Quantitative Structure-pharmacokinetics Relationship, QSPRQuantitative structure-pharmacokinetics relationship QSPR
Absorption, ADistribution, DMetabolism, MpH Excretion, E
Transport(Elimination) Disposition)
/ (Passive transport) (Carrier-mediated transport) (Membrane mobile transport )
/
//
TransportersMembrane Transport Proteins -ACEPepT1
Paracellular TransportTight Junction, TJ30100nm
6080 nm2938 nm23 nm
logD7.4pH
rifampicinrifamycinVdClrifabutin
710 m7 mMPS6090%2%10%3%10%50 nm
Drug Likeness
ADME
LipinskiThe LipinskiRule of Five
501000logDpKa
logPlogDlogPPlog PHanschLopPADME
pHlogDlogDlogPpKapH
IAMCaco-2MDCK
PAMPAUV
5%PAMPACaco-2PAMPA
11793242124641500110020
>5005100
>551
>1052
logP>5(ClogP)>4.15(MlogP)(51)
90%
(Rule of Five)
BayesianACDAvailable Chemicals Directory Database3500CMC3500CMC90%ACD10%MDDRMDL Drug Data Report80%
metoprololCYP2D6betaxolol
amlodipinefelodipinenifedipinenitrendipine
Solid DispersionInclusion CompoundsMicroemulsionsEmulsionMicroparticles Microcapsules MicrospheresNanoparticles Nanospheres NanocapsulesLiposomes
BCS
37pH1-7.5/D:S)250ml90%FDA/Caco-290%
Coating MaterialMembrane WallMicrocapsules/MicrospheresMicroparticles1250 mMicroencapsulation
(Nanospheres)(Nanocapsules)(Nanoparticles)101000nm
ADME/T
ADME/T
ADME/T
ADME/T
1964198431950.4%ADME/T
*2002FDA10030
*R&D
*QC
*
**