synthesis - rguhs：合成rguhs

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1、ENCLOSURE-I6.BRIEFRESUMEOFTHEINTENDEDWORK:6.1:Needforthestudy:Researchparticularlydrugdiscoveryisacontinuousprocessformanyreasonslike:a.Thedevelopmentofresistanceofdrugtherapycontinuestostimulatethesearchformoreeffectiveagents.b.Thoughsomeofthedrugsarehighlyeffectiveandtheyareassociatedwithsideef

2、fects.c.Somedrugsareallergictosomepersons.d.Naturealwayspossesproblemtohumanracesthroughnewerdiseases.Hencemanisalwaysinsearchofnewer,saferandmorepotentdrugsthantheexistingones.Thusthedrugdiscoveryisanewerendingprocess,henceisthepresentinvestigation.Thereisabetterunderstandingofthekinetics,orfact

3、orsthataffectthekinetics,ofthedifferentformsofPLA2.NewformsofPLA2arebeingdiscovered,suchasthecPLA2,whichfittheroleofanintracellularlyregulatedenzyme.MultipleformsofPLA2tendtocomplicatetheelucidationofthecellularmechanismsthatregulateAAreleaseandthesubsequenteicosanoidproduction.Becauseofthefactor

4、sthataffectPLA2kineticsandtheunknownnatureofthePLA2thatregulatesAArelease.10Thisreviewdiscussedselectedclassesofinhibitorsbecausethesehavegeneratedthemostintenseresearchinthefield.ThereisamultitudeofstructurallydiversecompoundsreportedintheliteraturethathavebeenreportedtobeinhibitorsofPLA2invitro

5、andsomehavebeenreportedtohaveanti-inflammatoryactivity.ItisclearfromabriefsurveyoftheliteraturethatthebulkofPLA2inhibitorshavetopicalanti-inflammatoryactivity.Thismaybeduetothenatureoftheseinhibitors:becausetheyarehydrophobictheymaybemorereadilyabsorbedintheskinwhereaswhengivenorallytheymaynotbea

6、bsorbed.Todata,manoalidehasbeenclinicallyevaluatedinmanandanewBristol-MyersSquibbretenoidderivativemayenterclinicaltrialsforpsoriasis;however,therearenoPLA2inhibitorsonthemarketorsignificantlyadvancedinclinicaldevelopment.Thisindicatesthelackofunderstandingofthisenzymeforthedevelopmentofrelevanti

7、nhibitors,whichisrelatedtothelackofunderstandingoftherelevantPLA2thatregulatesAAreleaseandeicosanoidbiosynthesis.TheconceptofregulationofeicosanoidbiosynthesisbyPLA2inhibitionanddecreasedAAavailabilitystillremainsaviab