Zogulitsa

Pawiri (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 ndi gulu lovuta komanso lodziwika bwino lomwe lingagwiritsidwe ntchito mosiyanasiyana mu Kafukufuku wamankhwala ndi chitukuko cha mankhwala.Pawiriyi ndi ya gulu lotchedwa azabicyclohexane carboxamides, omwe amadziwika kuti ali ndi zochitika zazikulu zamoyo.Ndi gulu la chiral, lomwe lili ndi ma stereocenters osiyanasiyana, owonetsedwa ndi (1R,2S,5S).Kukhalapo kwa chirality ndikofunikira chifukwa kumatha kukhudza kwambiri chilengedwe chapawiri komanso kugwirizana ndi zolinga zachilengedwe.Mmodzi yemwe angagwiritse ntchito mankhwalawa ndi cholinga chofuna kupanga ndi kupanga mankhwala atsopano.Mapangidwe ake apadera komanso stereochemistry amapereka mwayi wamaphunziro a ubale-ntchito (SAR) ndikuwongolera bwino.Ofufuza zamankhwala amatha kusintha magawo osiyanasiyana a molekyulu kuti afufuze momwe kusinthaku kumakhudzira kuyanjana kwake ndi zolinga zachilengedwe, monga ma enzyme, zolandilira, kapena zonyamula.Kudziwa kumeneku kungagwiritsidwe ntchito popanga mankhwala amphamvu komanso osankhidwa a matenda osiyanasiyana. Kuphatikiza apo, kapangidwe ka mankhwalawo akuwonetsa kuti akhoza kukhala ndi mphamvu yoletsa ma protease inhibitor.Ma protease ndi ma enzyme omwe amagwira ntchito yofunika kwambiri pazachilengedwe zosiyanasiyana ndipo amakhudzidwa ndi matenda monga khansa, HIV, ndi matenda otupa.Mapangidwe enieni ndi magulu ogwira ntchito a pawiriwa amachititsa kuti azikhala odalirika kuti apange zoletsa za protease ndi potency yabwino komanso kusankha.Kusintha kwapangidwe kungathe kupititsa patsogolo mphamvu zake zowononga tizilombo toyambitsa matenda kapena tizilombo toyambitsa matenda komanso kumapangitsa kuti pakhale mankhwala atsopano a antimicrobial.Mankhwala osokoneza bongo ndi osagwira ntchito kapena ocheperapo omwe amatha kusinthidwa kukhala mawonekedwe omwe ali mkati mwa thupi.Gulu la trifluoroacetyl limatha kukhala ngati gulu loteteza lomwe limatha kung'ambika kuti litulutse molekyulu yamankhwala yogwira ntchito pamalo omwe mukufuna.Njirayi imatha kupititsa patsogolo bioavailability ya mankhwalawa, kusungunuka, kapena kubweretsa kuzinthu zinazake. -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 imakhala ndi lonjezo ngati chinthu chofunikira pa kafukufuku wamankhwala ndi chitukuko cha mankhwala.Mapangidwe ake ovuta, stereochemistry, ndi magulu ogwira ntchito amapereka mipata yambiri yopangira ndi kupanga mankhwala atsopano, kufufuza zoletsa za protease, kupanga antimicrobial agents, ndi kugwiritsa ntchito njira zopangira mankhwala.Kufufuza kwina ndi kuwunika kwachilengedwe kwachilengedwe komanso kuthekera kwazamankhwala kungapangitse kuti pakhale zopambana m'malo osiyanasiyana achirengedwe.