含有四唑环的药物.pdf

该【含有四唑环的药物 】是由【amikiri】上传分享，beplayapp体育下载一共【9】页，该beplayapp体育下载可以免费在线阅读，需要了解更多关于【含有四唑环的药物 】的内容，可以使用beplayapp体育下载的站内搜索功能，选择自己适合的beplayapp体育下载，以下文字是截取该文章内的部分文字，如需要获得完整电子版，请下载此beplayapp体育下载到您的设备，方便您编辑和打印。:..pounds,,,2007DRUGSINTHETETRAZOLESERIES.(REVIEW)*,,:tetrazole,biologicalactivity,,-SUBSTITUTEDTETRAZOLES1--lactamantibioticsandopticallyactivetetrazole-containingantifungalpreparationsoftheazoletype,suchasTAK-456(1)[1,2].MeMeONNNNNNNNNFF1_______*,,Russia;e-mail:******@,FacultyofPharmacy,HradecKralove,CzechRepublic;e-mail:******@,,-13,January,,-3122/07/4301-0001?2007SpringerScience+BusinessMedia,:..Unlikefungicidalpreparationsofthefirst-andsecond-generationazoletypethetetrazole-containingpreparationsexhibithighactivityagainstCandida,us,-solubleformTAK-457forinjectionswasdevelopedonthebasisofTAK-456(1).Thepeakinthenumberofpublicationsonthissubjectin1997-2002wasfollowedinlateryearsbyadecay,-substitutedtetrazolesinthecreationofbiologicallyount,probably,--"nonclassicalisosterism"derivesfromtheconceptthatfunctionalgroupshavingsimilarphysicochemicalpropertiescanbeinterchangeable,,-substitutedtetrazolesareNHacidswhoseacidityconstantsdependlargelyonthesubstituentatposition5[3].Nevertheless,thepKavaluesof5-alkyl-and5-(~)[4],,ontheonehand,impedecontactandreducethecapacityforbondingwiththeactivecenter[5].Thus,[6].Nevertheless,–Losartan(2),andalargenumberofpapershavebeendedicatedtoit,.,[7-9].ItisassumedthatapreparationoftheLosartantypebindstothereceptorasaresultofthefactthattheblockermoleculeentersthelipophilic"pockets",bondingwithwhichrequiresthepresenceofanacidicfunctioninthemolecule,.,–K+22:..,amide,sulfamide,andothergroupswerenotsufficientlyeffectiveduringperoraladministration,[9,10].,andofthesethemostinterestingconcernthesearchforantihepatitis[11],hormonal[12],andantidiabetic[13]preparations,[14].HNHNNONNNNNArNC7F15NNHH34poundsdescribedin[13],inwhichthetetrazoleringisusedasareplacementforthecarboxylgroup,[15].,schizophrenia,andotherdiseasesofthecentralnervoussystemandmayalsoproveextremelyimportantforunderstandingtheirpharmacologyandthetherapeuticpotentialofthewholeclassofantagonistsandagonistsofglutamatereceptors[16].Atthepresenttimethesearchisgoingonforselectiveandnonselectiveantagonistsandpotentiatorsofalltypesofglutamatereceptors,-substituteddecahydroisoquinoline-3-carboxylicacids[17].NNHOONNOHNOHHHH2OHNNONHNNHNH56Studyofthebiologicalactivityshowedthatpreparation5isaneffectivemixedantagonistofAMPA–2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionicacidandkainatereceptorsandatthesametimehaslowerneurotoxicitythanknownantagonistsofAMPAandNMDA(N-methyl-D-asparticacid):..However,,eptedforclinicaltrials,anactivesearchisatpresentbeingmadeformoreeffectiveanalogs[18,19].-unsubstitutedtetrazole,theauthorsof[20,21]studiedits1-and2--substitutedderivativeswereagonistsofAMPAreceptors,whereasthe1-,studiedbytheauthorsof[22,23].--6-N-(1-iminoethyl)lysine(8)isaneffectiveinhibitorofNOS-2synthase,andthisincludeditsusewithperoraladministration.+Cl–-6-N-(1-iminoethyl)lysyl-5-tetrazolylamide9,whichisastablecrystallinesubstance,,butitissoontransformedintoL-6-N-(1-iminoethyl)lysine8asaresultofmetabolicprocesses(formice60%conversionin15min)[24,25].1,5-DISUBSTITUTEDTETRAZOLESWhereas5-substitutedtetrazoleshavefounduseasisostericreplacementsofacarboxylgroup,1,5-disubstitutedtetrazolescanbeusedasisosteresofthecis-amidebondofpeptides[26].NONNHHNONOHNNRRRRRRRNROOH4:..Asaresultofstudyoftheamidesandthecorrespondingtetrazolesitwasshownthatthenewtetrazole-,however,,5-disubstitutedtetrazolesasisostericreplacementsofthecis-amidebondofpeptidesitisnecessarytomentionthesynthesisofHIV-proteaseinhibitors[27].Nevertheless,biologicallyactivesubstancescontaininga1,5--poundsalsoexhibitweakantiulcerandanalgesicactivity[28].Anotherexampleofanti-poundsoftype11describedin[29].poundsistheblockingofthereceptorsofchemokines(ytokines),'-(5-amino-1,2,3,4-tetrazol-4-yl)-3'-deoxythymidines12,whichexhibitactivityagainstthehumanimmunedeficiencyvirus,wasdevelopedbyBayerAG[30].OMeHNHOONONNHRNNN12Theabove-mentionedexamplesofpreparationscontaininga1,5--substituted5--substituted5-thiotetrazolefragmentistheβ-lactamantibioticsofthecephalosporinclass[31,32].-lactamringwithvarioussubstituentsatpositions3and7,-oxadethiacephalosporinclasscontaininga5-thiotetrazolepound13(Latamoxef).5:..-substituted5--5-,whichareeffectiveagainstulcerscausedbyaceticacidderivatives(.,indomethacin)[33].NNNS(O)nNNHONO(CH2)nOS14NNMen=0,215NNpoundswerestudiedforantiulceractivity[34].Theauthorsestablishedthatthepoundswerederivativesof1-substituted5--thiotetrazoleswasstudiedin[35-37].,asaresultoftheinvestigationsitwassuggestedthatthedisulfidefragmentbetweenthetwoelectron-[38].Compounds16withvarioussubstituentsatposition1ofthetetrazoleringwerestudiedbytheauthorsof[39].Suchproductscanbeusedasantihypertensiveagents,:..HNNOONHNHRNNHMeSNN162,5-DISUBSTITUTEDTETRAZOLESThereisverylittleinformationontheuseof2,5-disubstitutedtetrazolesinthesynthesisofbiologicallyactivepreparations,,5-disubstitutedtetrazolesitisnecessarytosingleoutreportsonderivativesof9H-xanthene-9-carboxylicacid17,inwhichthetetrazoleisare