药化英文简介

MedicinalchemistryMedicinalorpharmaceuticalchemistryisadisciplineattheintersectionofchemistryandpharmacologyinvolvedwithdesigning,synthesizinganddevelopingpharmaceuticaldrugs.Medicinalchemistryinvolvestheidentification,synthesisanddevelopmentofnewchemicalentitiessuitablefortherapeuticuse.Italsoincludesthestudyofexistingdrugs,theirbiologicalproperties,andtheirquantitativestructure-activityrelationships(QSAR).Pharmaceuticalchemistryisfocusedonqualityaspectsofmedicinesandaimstoassurefitnessforthepurposeofmedicinalproducts.Compoundsusedasmedicinesareoverwhelminglyorganiccompoundsincludingsmallorganicmoleculesandbiopolymers.However,inorganiccompoundsandmetal-containingcompoundshavebeenfoundtobeusefulasdrugs.Forexample,thecis-platinseriesofplatinium-containingcomplexeshavefounduseasanti-canceragents.Medicinalchemistryisahighlyinterdisciplinarysciencecombiningorganicchemistrywithbiochemistry,computationalchemistry,pharmacology,pharmacognosy,molecularbiology,statistics,andphysicalchemistry.ProcessofdrugdiscoveryDiscoveryThefirststepofdrugdiscoveryinvolvestheidentificationofnovelactivecompounds,oftencalledhits,whicharetypicallyfoundbyscreeningmanycompounds(compoundlibrary)forthedesiredbiologicalproperties.Whileanumberofapproachestowardtheidentificationofhitsexist,themostsuccessfuloftechniquesreliesonchemicalandbiologicalintuitiondevelopedthroughyearsofrigorouschemical-biologicaltraining.Othersourcesofhitscancomefromnaturalsources,suchasplants,animals,orfungi.Hitsmayoriginatealsofromrandomchemicallibraries,suchasthosecreatedthroughcombinatorialchemistryorhistoricchemicalcompoundcollectionsthataretesteden-masseagainstthebiologicaltargetinquestionOptimizationAnotherstepindrugdiscoveryinvolvesfurtherchemicalmodificationsinordertoimprovethebiologicalandphysiochemicalpropertiesofagivencandidatecompoundlibrary.Chemicalmodificationscanimprovetherecognitionandbindinggeometries(pharmacophores)ofthecandidatecompounds,theiraffinitiesandpharmacokinetics,orindeedtheirreactivityandstabilityduringtheirmetabolicdegradation.Anumberofmethodshavecontributedtoquantitativemetabolicprediction,andarecentexampleisSPORCalc[1].Thequantitativestructure-activityrelationship(QSAR)ofthepharmacophoreplayanimportantpartinfindingleadcompounds,whichexhibitthemostpotency,mostselectivity,bestpharmacokineticsandleasttoxicity.QSARinvolvesmainlyphysicalchemistryandmoleculardockingtools(CoMFAandCoMSIA),thatleadstotabulateddataandfirstandsecondorderequations.Therearemanytheories,themostrelevantbeingHansch'sanalysisthatinvolvesHammettelectronicparameters,stericparametersandlogP(lipophilicity)parameters.DevelopmentThefinalstepinvolvestherenderingtheleadcompoundssuitableforuseinclinicaltrials.Thisinvolvestheoptimizationofthesyntheticrouteforbulkproduction,andthepreparationofasuitabledrugformulation.TraininginmedicinalchemistryManyworkersinthefielddonothaveformaltraininginmedicinalchemistry.AlthoughseveralgraduateschoolsandCollegesofPharmacyofferformalPh.D.programsinmedicinalchemistry,frequentlythebroadereducationinachemistrygraduateprogramcanprovidemanyoftheskillsneeded.Amajorityofworkingmedicinalchemistshavedegreesinorganicchemistry,ratherthanmedicinalchemistry.[2]MedicinalChemistryisamultifaceteddisciplinethatencompassessyntheticorganicchemistry,naturalproductschemistry,enzymology,chemicalbiology,structuralbiologyandcomputationalmethods,allofwhichareaimedatthediscoveryanddevelopmentofnewtherapeuticagents.Medicinalchemistryisbynatureaninterdisciplinaryscience,andpractitionershaveastrongbackgroundinorganicchemistry,coupledwithabroadunderstandingofbiologicalconceptsrelatedtocellulardrugtargets.Scientistsinthefieldarewellpositionedtoworkaspartofaninterdisciplinaryteamthatuseschemicalstructuralprinciplestodesigneffectivedrugsanddiagnosticagents.Graduate(Master'sandPh.D.)levelprogramsinmedicinalchemistrycanbefoundintraditionalmedicinalchemistrydepartments,orinpharmaceuticalsciencesdepartments,bothofwhicharetraditionallyassociatedwithschoolsofpharmacy.Somechemistrydepartmentsalsohaveprogramsinmedicinalchemistry,butstudentsareoftennotexposedtoimportantbiologicalprinciplesthatarenecessaryforasuccessfulcareerindrugdiscovery.Someworkersinthefielddonothaveformaltraininginmedicinalchemistry,andreceivethenecessarybiologicalbackgroundafteremployment.Postdoctoraleducationof2–3yearsistypicalafterreceivingaPh.D.inmedicinalchemistry.EmploymentprospectsattheMaster'slevelaregoodinthepharmaceuticalindustry,andatthePh.D.level,opportunitiesforemploymentinacademia,industryorgovernmentareavailableTextTwoGlossaryofTermsUsedinMedicinalChemistry（2）(IUPACRecommendations1998)1，IND:AbbreviationforInvestigationalNewDrug.2，Intrinsicactivity:Intrinsicactivityisthemaximalstimulatoryresponseinducedbyacompoundinrelationtothatofagivenreferencecompound.3，Thistermhasevolvedwithcommonusage.ItwasintroducedbyAriënsasaproportionalityfactorbetweentissueresponseandreceptoroccupancy.Thenumericalvalueofintrinsicactivity(alpha)couldrangefromunity(forfullagonists,i.e.,agonistinducingthetissuemaximalresponse)