藥物化學(xué)先導(dǎo)化合物的發(fā)現(xiàn)課件

第二節(jié)先導(dǎo)化合物的發(fā)現(xiàn)LeaddiscoveryVaudononlychAsposeslidesforNET4odientPEvaluationonly.CreatedwithAsposeSlidesforNET4.0dientProfilo71Copyright2019-2019AsposePtyL■新藥開發(fā)過程的幾個階段先導(dǎo)化合物的探索和選定階段臨床前實(shí)驗(yàn)研究階段臨床研究(臨床治療和效果驗(yàn)證階段)醫(yī)藥生產(chǎn)申請及審批階段售后效果以及副作用的調(diào)查統(tǒng)計階段藥品合理性再審查階段VaudononlychAsposeslidesforNET4odientPEvaluationonly.CreatedwithAsposeSlidesforNET4.0dientProfilo71Copyright2019-2019AsposePtyL新藥的定義口新的化學(xué)實(shí)體INewChemicalEntity,NCE口新的藥用化合物口制成各種制劑供臨床上使用VaudononlychAsposeslidesforNET4odientPEvaluationonly.CreatedwithAsposeSlidesforNET4.0dientProfilo71Copyright2019-2019AsposePtyLNewChemicalEntityaAnewchemicalentity(nce)isacompoundnotpreviouslydescribedintheliteratureVaudononlychAsposeslidesforNET4odientPEvaluationonly.CreatedwithAsposeSlidesforNET4.0dientProfilo71Copyright2019-2019AsposePtyL新藥的藥物化學(xué)研究分兩個階段口發(fā)現(xiàn)先導(dǎo)化合物(LeadGeneration)■為尋求新的先導(dǎo)化合物(LeadCompound)■類型衍化口對先導(dǎo)化合物進(jìn)行優(yōu)化LeadOptimization)■尋找該先導(dǎo)化合物系列衍生物中的最佳化合物■系列設(shè)計VaudononlychAsposeslidesforNET4odientPEvaluationonly.CreatedwithAsposeSlidesforNET4.0dientProfilo71Copyright2019-2019AsposePtyLLeadgeneration口發(fā)現(xiàn)先導(dǎo)化合物aLeadgenerationisthetermappliedtostrategiesdevelopedtoidentifycompoundswhichpossessadesiredbutnon-optimizedbiologicalactivityVaudononlychAsposeslidesforNET4odientPEvaluationonly.CreatedwithAsposeSlidesforNET4.0dientProfilo71Copyright2019-2019AsposePtyLLeadoptimization口先導(dǎo)化合物進(jìn)行優(yōu)化oLeadoptimizationisthesyntheticmodificationofabiologicallyactivecompoundtofulfillallstereoelectronicphysicochemical,pharmacokineticandtoxicologicrequiredforclinicalusefulness.VaudononlychAsposeslidesforNET4odientPalvetonoCreatedwithAsposeSlidesforNET4.0dientProfilo71Copyright2019-2019AsposePtyL相互關(guān)系口先導(dǎo)化合物的發(fā)現(xiàn)■為尋找最佳化合物提供了基礎(chǔ)和新的結(jié)構(gòu)類型口先導(dǎo)化合物優(yōu)化1先導(dǎo)化合物的深入和發(fā)展口兩者相輔相成VaudononlychAsposeslidesforNET4odientPEvaluationonly.CreatedwithAsposeSlidesforNET4.0dientProfilo71Copyright2019-2019AsposePtyL先導(dǎo)化合物(LeadingCompound)口又稱原形物prototypecompound是指有獨(dú)特結(jié)構(gòu)的具所期望的生物或藥理活性的化合物但會存在一些其他所不合適的性質(zhì)可能因?yàn)榛钚蕴?選擇性不高,或藥代動力學(xué)性質(zhì)不好,不能作為新藥開發(fā)但可以在該化合物結(jié)構(gòu)基礎(chǔ)上,進(jìn)行一系列的結(jié)構(gòu)改造或修飾,得到符合治療要求的新藥VaudononlychAsposeslidesforNET4odientPEvaluationonly.CreatedwithAsposeSlidesforNET4.0dientProfilo71Copyright2019-2019AsposePtyL口先導(dǎo)化合物的來源大體可分為兩方面■天然產(chǎn)物■人工合成VaudononlychAsposes