Iimveliso

Ikhompawundi (1R,2S,5S)-N-[(1S)-1-cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl]-3-[(2S)-3,3- i-dimethyl-2-[(2,2,2-trifluoroacetyl)amino]butanoyl]-6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxamide yikhompawundi entsonkothileyo kwaye ecaciswe kakhulu enezixhobo ezahlukeneyo ezinokusetyenziswa uphando lwamayeza kunye nophuhliso lwamachiza.Le khompawundi yeyodidi olubizwa ngokuba yi-azabicyclohexane carboxamides, eyaziwa ngokuba inomsebenzi obalulekileyo webhayoloji.Yikhompawundi ye-chiral, equlethe i-stereocenters eyahlukeneyo, eboniswa yi-(1R,2S,5S) ukutyunjwa.Ubukho bobubele bubalulekile njengoko bunokuba nefuthe elibonakalayo kwiipropathi zebhayoloji zekhompawundi kunye nokusebenzisana nethagethi yebhayoloji.Okunye okunokwenzeka kokusetyenziswa kwale khompawundi kujoliso ekuyileni nasekuhlanganiseni amachiza anoveli.Ubume bayo obukhethekileyo kunye ne-stereochemistry ibonelela ngamathuba okufunda ngobudlelwane bomsebenzi wobume (SAR) kunye nokuqhubela phambili.Abaphandi bamachiza banokuguqula imimandla eyahlukeneyo ye-molecule ukuphanda ukuba olu tshintsho luchaphazela njani ukusebenzisana kwayo kunye neethagethi zebhayoloji, ezifana ne-enzymes, i-receptors, okanye abathuthi.Olu lwazi lunokuthi ke lusetyenziswe ekuphuhliseni amachiza anamandla nakhethiweyo ezifo ezahlukeneyo. Ngaphaya koko, ulwakhiwo lwekhompawundi lucebisa ukuba lunokuba namandla njenge-protease inhibitor.Iiproteases ziienzymes ezidlala indima ebalulekileyo kwiinkqubo ezahlukeneyo zebhayoloji kwaye zibandakanyeka kwizifo ezinjengomhlaza, i-HIV, kunye nokuphazamiseka kokudumba.Ukucwangciswa okuthe ngqo kunye namaqela asebenzayo ale khompawundi kwenza kube ngumviwa othembisayo wokuphuhlisa i-protease inhibitors kunye ne-potency ephuculweyo kunye nokukhetha.Ukongezelela, ubukho be-compound yeqela le-cyano kunye nendandatho ye-pyrrolidine ibonisa ukuba ingaba nomsebenzi wokulwa ne-bacterial or fungal infections.Ukuguqulwa kwesakhiwo kunokwenziwa ukunyusa iimpawu zayo zokulwa ne-antibacterial okanye i-antifungal kunye nokukhokelela ekuphuhliseni i-antimicrobial agents ezintsha.Ngaphezu koko, ubukho beqela le-trifluoroacetyl lithetha ukuba i-compound ingaba namandla njengeprodrug.Iimveliso zingasebenzi okanye zingaphantsi kweekhompawundi ezinokuthi ziguqulwe zibe yifom esebenzayo ngaphakathi komzimba.Iqela le-trifluoroacetyl linokusebenza njengeqela elikhuselayo eligqunyiweyo elinokucolwa ukukhulula imolekyuli yechiza esebenzayo kwindawo efunwayo yesenzo.Esi sicwangciso sinokuphucula i-bioavailability yeziyobisi, i-solubility, okanye ukuhanjiswa kwezicubu ezithile. -3-yl]ethyl] -3-[(2S) -3,3-dimethyl-2-[(2,2,2-trifluoroacetyl)amino]butanoyl]-6,6-dimethyl-3-azabicyclo[3.1. I-0]hexane-2-carboxamide inesithembiso njengekhompawundi exabisekileyo kuphando loxubo mayeza kunye nophuhliso lwamachiza.Ubume bayo obuntsonkothileyo, i-stereochemistry, kunye namaqela asebenzayo anika amathuba amaninzi okuyila kunye nokudibanisa amachiza anoveli, ukuhlola inhibition ye-protease, ukuphuhlisa i-antimicrobial agents, kunye nokusetyenziswa kwezicwangciso zeprodrug.Uphando olongezelelekileyo kunye nokuphononongwa kwemisebenzi yebhayoloji kunye nokubanakho kwekhemesti kunokukhokelela kwimpumelelo kwiindawo ezahlukeneyo zonyango.