Naslov
Synthesis of the second generation of primaquine bis-ureas bearing hydroxyalkyl/hydroxyaryl moieties
(Synthesis of the second generation of primaquine bis-ureas bearing hydrxyalkyl/hydroxyaryl moieties)

Autori
Pavić, Kristina ; Rajić, Zrinka ; Perković, Ivana ; Zorc, Branka

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
EFMC-ISMC 2018 Book of Abstracts / - , 2018, 331-331

Skup
EFMC International Symposium on Medicinal Chemistry 2018

Mjesto i datum
Ljubljana, Slovenija, 02.09.2018. - 06.09.2018

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
primaquine ; aminoalcohols ; synthesis ; bis-urea

Sažetak
In several papers published by our research group, we have described the preparation of various primaquine (PQ) derivatives and reported their antiproliferative, antioxidative, antimalarial, antimicrobial and/or antiviral activities[1]. A great number of compounds, members of different classes of PQ derivatives, namely amides, ureas, bis- ureas, acylsemicarbazides, showed prominent antiproliferative activities, with acylsemicarbazides and bis-ureas being more active than corresponding amides and ureas. Among synthesized PQ derivatives, urea with 5- hydroxypentyl substituent exerted remarkable antiproliferative activity against human colon adenocarcinoma SW620 cell line (IC50 = 0.2 µM). Having in mind all the above mentioned facts, we have designed and synthesized a second generation of bis-urea PQ derivatives where PQ core and a spacer type are preserved, but aminoalcohol part of the molecule is replaced by (a) more rigid aminoalcohols bearing small cycloalkane moieties, (b) fluoro substituted aminoalcohols or (c) aminophenol. In particular, organofluorine compounds are very interesting candidates in drug discovery since they tend to have improved metabolic stability, physicochemical properties, bioavailability and/or biological activity[2]. In the first reaction step, PQ-benzotriazolide 2 was synthesized in the reaction of PQ and 1- benzotriazole carboxylic acid chloride (BtcCl, 1). Following our previously described procedure, PQ semicarbazide 3 was prepared from compound 2 and hydrazine. Compound 3 reacted with BtcCl giving benzotriazolide 4 which was used without further purification in the next reaction step with aminoalcohols/aminophenol yielding bis-ureas 5a-f. This reaction was performed in dioxane in the presence of an equimolar amount of triethylamine (TEA) if the reaction included aminoalcohol or aminophenol, or two equivalents of TEA if aminoalcohol was in the form of a salt. Structures of all new compounds were confirmed by standard methods (IR, 1H, 13C NMR, MS). Evaluation of their antiproliferative and antimalarial activity is in progress.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Farmacija

POVEZANOST RADA