Alaabta

Xarunta (1R,2S,5S)-N-[(1S) -1-cyano-2-[(3S) -2-oxopyrrolidin-3-yl] ethyl]-3-[(2S)-3,3- dimethyl-2-[(2,2,2-trifluoroacetyl) amino] butanoyl] -6,6-dimethyl-3-azabicyclo[3.1.0] hexane-2-carboxamide waa xarun adag oo aad u gaar ah oo leh codsiyo kala duwan oo suurtagal ah cilmi baadhisyo dawooyinka iyo horumarinta daroogadaWaa iskudhis chiral ah, oo ka kooban stereocenters kala duwan, oo lagu tilmaamay (1R,2S,5S).Joogitaanka chirality waa muhiim sababtoo ah waxay si weyn u saameyn kartaa sifooyinka bayooloji ee xarunta iyo la dhexgalka bartilmaameedyada noolaha.Qaab-dhismeedkeeda gaarka ah iyo stereochemistry waxay bixiyaan fursado daraasadaha qaab-dhismeedka-shaqada (SAR) iyo hagaajinta rasaasta.Cilmi-baarayaasha dawooyinka ayaa wax ka beddeli kara gobollada kala duwan ee molecule-ka si ay u baaraan sida isbeddelladani u saameeyaan isdhexgalka ay la leeyihiin bartilmaameedyada noolaha, sida enzymes, reseptors, ama gaadiidleyda.Aqoontan ayaa markaa loo isticmaali karaa si loo horumariyo dawooyin awood badan oo xulasho ah oo loogu talagalay cudurro kala duwan. Intaa waxaa dheer, qaab-dhismeedka xaruntu waxay soo jeedinaysaa in laga yaabo inay leedahay awood ka hortag ah protease.Proteases waa enzymes kuwaas oo door muhiim ah ka ciyaara hababka noolaha ee kala duwan waxayna ku lug leeyihiin cudurrada sida kansarka, HIV, iyo xanuunka bararka.Habaynta gaarka ah iyo kooxaha shaqada ee xaruntan waxay ka dhigayaan musharaxa rajo-gelinta ah ee horumarinta protease-ka-horumarineed ee awoodda iyo xulashada xulashada. Intaa waxaa dheer, joogitaanka xarunta ee koox cyano ah iyo giraanta pyrrolidine waxay soo jeedinayaan in laga yaabo in ay yeelato waxqabad ka hortagga caabuqyada bakteeriyada ama fungal.Wax ka beddelka qaabdhismeedka ayaa la samayn karaa si kor loogu qaado sifooyinka bakteeriyada ama antifungal waxayna u horseedaa horumarinta wakiilada cusub ee antimicrobial.Intaa waxaa sii dheer, joogitaanka kooxda trifluoroacetyl waxay tusinaysaa in xaruntu ay yeelan karto karti sida soosaar.Daroogooyinku waa xeryahooda aan firfircoonayn ama firfircoonayn kuwaas oo loo bedeli karo qaabka firfircoon ee jidhka dhexdiisa.Kooxda trifluoroacetyl waxay u adeegi kartaa sidii koox ilaalin ah oo daboolan oo la kala furfuri karo si loo sii daayo molecule daroogada firfircoon ee goobta la rabo ee ficilka.Istaraatiijiyadani waxay hagaajin kartaa bioavailability daroogada, milanka, ama gaarsiinta unugyo gaar ah. Gebogebadii, xarunta (1R,2S,5S) -N-[(1S) -1-cyano-2-[(3S) -2-oxopyrrolidin -3-yl] ethyl] -3-[(2S) -3,3-dimethyl-2-[(2,2,2-trifluoroacetyl) amino] butanoyl]-6,6-dimethyl-3-azabicyclo[3.1. 0]hexane-2-carboxamide waxay ballan qaadaysaa sidii xarun qiimo leh oo ku jirta cilmi-baarista dawooyinka iyo horumarinta daroogada.Qaab dhismeedkeeda kakan, stereochemistry, iyo kooxaha shaqeeya waxay soo bandhigaan fursado badan oo loogu talagalay naqshadaynta iyo isku-dhafka dawooyinka cusub, sahaminta ka-hortagga borotiinka, horumarinta wakiilada antimicrobial, iyo adeegsiga xeeladaha daroogada.Cilmi-baadhis dheeraad ah iyo sahaminta hawlaheeda bayooloji iyo awooddeeda dawooyinka ayaa laga yaabaa inay horseeddo horumarro laga gaaro meelo kala duwan oo daweyn ah.