Imikhiqizo

I-6-Acetyl-8-cyclopentyl-5-methyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]pyrido[2,3-d]pyrimidin-7(8H)-i-hydrochloride eyodwa iyinhlanganisela ngezicelo ezingase zibe khona ocwaningweni lwezemithi nokuthuthukiswa kwezidakamizwa.Isakhiwo sayo samangqamuzana esiyingqayizivele sinikeza amathuba ophenyo mayelana nokusetshenziswa kwayo kokwelapha.Le nhlanganisela iyingxenye yomndeni we-pyrido[2,3-d]pyrimidinone, esifundwe kabanzi ngenxa yemisebenzi yawo yezemithi.Ukuba khona kweqembu le-acetyl kuphakamisa ukusebenzisana okungenzeka nama-enzyme ahilelekile ezinqubweni zamaselula.Ingase ibe nemiphumela evimbelayo kuma-enzyme afana nama-kinases noma ama-protease, okuyenza ibe ikhandidethi ethembisayo ekuthuthukisweni kwama-enzyme-specific inhibitors.Amaqembu e-cyclopenyl kanye ne-methyl esakhiweni anegalelo kumvelo ye-lipophilic ye-compound.Lesi sakhiwo siyivumela ukuthi inqamule kalula izithiyo zebhayoloji, ikhulise amandla ayo njengekhandidethi lezidakamizwa.Ingase ibe nokufinyeleleka okuthuthukisiwe kanye nokutholakala kwe-bioavailability, okwenza ifanelekele ukuphathwa komlomo kanye nokusabalalisa okuhlelekile.Iqembu le-1-piperazinyl kanye ne-2-pyridinyl elikhona ku-compound inikeza ukuguquguquka kokusetshenziswa kwayo okungenzeka ekuklanyeni izidakamizwa.Okuphuma kokuphuma ku-Piperazine kuqashelwa kabanzi kukhemikhali yezokwelapha ngemisebenzi yabo yebhayoloji.Iqembu le-piperazine lingakwazi ukufaka isandla ekubopheni i-receptor futhi liguqule izakhiwo ze-pharmacokinetic.Ngaphezu kwalokho, iqembu le-pyridine livame ukuhileleka ekusebenzisaneni kwe-ligand-receptor, njengoba izinhlelo zendandatho ye-pyridine zingakha izibopho ze-hydrogen nezindawo ezithile zokwamukela.Lezi zakhiwo zenza le nhlanganisela ibe yi-ligand engaba khona yama-receptor ahlukahlukene, okuhlanganisa ama-receptors ahlanganiswe ne-G amaprotheni. Ngokucabangela i-pyrido [2,3-d] scaffold ye-pyrimidinone kanye nokuba khona kweqembu le-piperazine, i-compound ingabhekwa njenge-ejenti elwa nomdlavuza. .Ingase ibonise imiphumela ye-cytotoxic ngokumelene namaseli omdlavuza ngokuvinjelwa kwezindlela ezithile zokubonisa ezihambisana nokwanda kwamaseli.Ucwaningo olwengeziwe olubandakanya amamodeli e-in vitro kanye ne-vivo lungahlola amandla ayo njenge-ejenti elwa nesimila.Ukwengeza, umgogodla we-pyrido[2,3-d]pyrimidinone we-compound ungashintshwa ukuze uqondise izifo noma izimo ezithile.Ngokwethula amaqembu asebenzayo afanelekile noma ama-substituents, ukukhetha kwawo namandla kungathuthukiswa, okuvumela ukuthuthukiswa kwama-ejenti okwelapha akhethekile. i-piperazinyl) -2-pyridinyl]amino]pyrido[2,3-d]pyrimidin-7(8H) -i-hydrochloride eyodwa inamandla ezindaweni eziningi zocwaningo lwezemithi.Izici zayo zesakhiwo zivumela uphenyo ekuvimbeleni ama-enzyme, ukubopha ama-receptor, nomsebenzi wokulwa nomdlavuza.Ukuhlola okwengeziwe kanye nokwenza kahle kwesakhiwo sayo esiyinhloko kungase kuveze amakhandidethi amasha ezidakamizwa anekhono elithuthukisiwe kanye nezici ezithile ezihlosiwe zezokwelapha ezihlukahlukene.