Dizajn, sinteza i evaluacija farmakokinetički relevantnih svojstava novih spirohidantoina izvedenih iz β-tetralona

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Anita M. Lazić
Željko D. Mandić
Nataša V. Valentić
Gordana S. Ušćumlić
Nemanja P. Trišović

Abstract

U cilju kreiranja novih antikonvulzivnih lekova, sintetisana je serija spirohidantoina izvedenih iz β-tetralona koji u položaju 3 hidantoinskog prstena sadrže 4-supstituisanu benzil-grupu (1a1g) ili 2-(4-supstituisanu fenil)-2-oksoetil-grupu (2a2f). Hemijska struktura novo­sintetisanih molekula potvrđena je određivanjem temperature topljenja, kao i primenom infracrvene spektroskopije sa Furijeovom transformacijom, protonske nuklearne magnetne rezonancije, nuklearne magnetne rezonancije ugljenika-13, UV-vidljive spektroskopije i elementarne analize. Efekat supstituenata na pomeranje apsorpcionih maksimuma jedinjenja 1a1g i 2a2f analiziran je Hametovom (Hammett) jednačinom. Uticaj hemijske strukture na farmakološke osobine derivata hidantoina procenjen je primenom "pravila broja pet", Veberovog (Veber), Eganovog (Egan) i Gozovog (Ghose) empirijskog kriterijuma, kao i primenom različitih in silico metoda. U poređenju sa referentnim lekom fenitoinom, derivati koji u svojoj strukturi sadrže atome halogena ili elektron-donorske grupe, trebalo bi da ispoljavaju najbolju intestinalnu apsorpciju i prolazak kroz krvno-moždanu barijeru. U zavisnosti od prirode supstituenta prisutnog u p-položaju fenilnog jezgra, derivati 1a1g i 2a2f mogu da budu potencijalni aktivatori/inhibitori pojedinih izoenzima citohroma P450.

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How to Cite
Lazić, A. M., Mandić, Željko D., Valentić, N. V., Ušćumlić, G. S., & Trišović, N. P. (2019). Dizajn, sinteza i evaluacija farmakokinetički relevantnih svojstava novih spirohidantoina izvedenih iz β-tetralona. HEMIJSKA INDUSTRIJA (Chemical Industry), 73(2), 79–92. https://doi.org/10.2298/HEMIND181203007L
Section
Chemical Engineering - Pharmaceutical Engineering

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