Imikhiqizo

4--[6-(6-bromo-8-cyclopentyl-5-methyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]- i-piperazine-1-carboxylic acid tert-butyl ester iyinhlanganisela engase isetshenziswe ocwaningweni lwezemithi nasekuthuthukisweni kwezidakamizwa.Isakhiwo sayo esiyinkimbinkimbi kanye namaqembu asebenzayo anikeza amathuba ahlukahlukene ophenyo kanye nokuhlolwa kwezicelo zayo zokwelapha.Okunye okungase kube khona ukusetshenziswa kwalesi sakhi emkhakheni we-oncology.Ukuba khona kweqembu le-bromo kanye ne-pyrido[2,3-d]pyrimidin moiety kuphakamisa ukuthi ingase ibe nomsebenzi wokulwa nomdlavuza.Iqembu le-bromo laziwa ngamandla alo okuvimbela ukukhula kwamaselula futhi lenze i-apoptosis kumaseli omdlavuza.Ukwengeza, i-pyrido[2,3-d]pyrimidin scaffold iye yahlotshaniswa nemiphumela elwa nokwanda kanye ne-anti-tumor.Ngakho-ke, le nhlanganisela ingaqhubeka ifundelwa amandla ayo njenge-ejenti ye-anti-cancer inoveli.Ngaphezu kwalokho, amaqembu e-cyclopenyl kanye ne-methyl akhona esakhiweni enza i-lipophilic ehlanganisiwe, engase ibe nomthelela ekutheni ikwazi ukuwela izithiyo zezinto eziphilayo, njengegazi. -umgoqo wobuchopho.Le ndawo ivula ithuba lokuyisebenzisa ekuthuthukisweni kwezidakamizwa ezibhekiswe ezifweni zesimiso sezinzwa esiyinhloko, njengokuphazamiseka kwezinzwa.I-compound ingashintshwa ukuze ithuthukise ukukhetha kwayo kanye namandla ngokumelene nezinhloso ezithile ezihilelekile kulezi zifo.Ngaphezu kwalokho, ukuba khona kwe-piperazine-1-carboxylic acid tert-butyl ester moiety kubonisa ukuthi i-compound ingaba nensizakalo njenge-prodrug.Izidakamizwa ziyizinhlanganisela ezingasebenzi ezingaguqulwa zibe amafomu asebenzayo ngaphakathi emzimbeni.Iqembu le-tert-butyl ester lingasebenza njengeqembu elivikelayo, livimbele ukwenziwa kusebenze ngaphambi kwesikhathi komuthi ngaphambi kokuthi ufinyelele endaweni oyifunayo.Uma ifinyelela izicubu ezihlosiwe noma amangqamuzana, iqembu le-ester lingahlukaniswa nge-enzymatic, likhulule i-molecule yezidakamizwa esebenzayo.Ngaphezu kwalokho, i-compound's pyridine kanye ne-pyrimidine moieties ibonisa amandla ayo njenge-pharmacophore yokuklama ama-inhibitors akhethiwe ama-enzyme noma ama-receptors athile.Lezi zingasukela kuma-kinases kuye kuma-G protein-coupled receptors, kuye ngokuguqulwa okwenziwe esakhiweni esiwumgogodla.Le nhlanganisela ingasebenza njengesiqalo sezifundo zobudlelwano besakhiwo-umsebenzi futhi iholele ekuthuthukisweni kwama-inhibitors anamandla futhi akhethiwe kuzinhloso ezithile zokwelapha.Kafushane, 4--[6-(6-bromo-8-cyclopentyl-5-methyl-7) -oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-2-ylamino)-pyridin-3-yl]-piperazine-1-carboxylic acid tert-butyl ester ibonisa amandla ezindaweni ezihlukahlukene zocwaningo lwezemithi.Isakhiwo sawo esiyingqayizivele kanye namaqembu asebenzayo angacutshungulwa ngokuqhubekayo ngomsebenzi wokulwa nomdlavuza, ukuthuthukiswa kwezidakamizwa zesimiso sezinzwa esimaphakathi, amasu e-prodrug, kanye ne-enzyme ekhethiwe noma inhibition ye-receptor.Uphenyo oluqhubekayo kanye nokwenza kahle kwalesi sithako kungase kuholele ekutholakaleni kwezinketho ezintsha zokwelapha ngokusebenza okuthuthukisiwe kanye nokucaciswa okuhlosiwe.