Počet záznamů: 1
Polysubstituted Pyrimidines as Potent Inhibitors of Prostaglandin E2 Production: Increasing Aqueous Solubility
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SYSNO ASEP 0543665 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Polysubstituted Pyrimidines as Potent Inhibitors of Prostaglandin E2 Production: Increasing Aqueous Solubility Tvůrce(i) Kalčic, Filip (UOCHB-X) RID, ORCID
Kolman, Viktor (UOCHB-X) RID
Zídek, Zdeněk (UEM-P)
Janeba, Zlatko (UOCHB-X) RID, ORCIDZdroj.dok. ChemMedChem. - : Wiley - ISSN 1860-7179
Roč. 16, č. 18 (2021), s. 2802-2806Poč.str. 5 s. Jazyk dok. eng - angličtina Země vyd. DE - Německo Klíč. slova anti-inflammatory ; prostaglandin E2 ; pyrimidines ; solubility ; synthesis Obor OECD Organic chemistry CEP TE01020028 GA TA ČR - Technologická agentura ČR Způsob publikování Omezený přístup Institucionální podpora UOCHB-X - RVO:61388963 ; UEM-P - RVO:68378041 UT WOS 000663235700001 EID SCOPUS 85108182828 DOI 10.1002/cmdc.202100263 Anotace Water solubility is one of the key features of potential therapeutic agents. In order to enhance the low water solubility of the parent 5-butyl-4-(4-methoxyphenyl)-6-phenylpyrimidin-2-amine, a potent inhibitor of prostaglandin E2 (PGE2) production, we synthesized and evaluated a new series of derivatives in which the butyl group at the C5 position of the pyrimidine ring was replaced with a less lipophilic substituent, preferably with a hydrophilic aliphatic moiety. Except for the 5-cyanopyrimidine derivative, all target compounds exhibited increased (2.7 – 87-fold) water solubility relative to the parent compound. Although nontoxic in mouse peritoneal cells, the prepared compounds were either equipotent or weaker inhibitors of PGE2 production than the parent compound. The most promising compound from the series was found to be the 5-(2,5,8,11-tetraoxadodecyl)pyrimidine derivative (with three polyethylene glycol units at the C5 position), which exhibited 32-fold higher water solubility and only slightly weaker inhibitory activity (22 % of remaining PGE2 production) compared with the parent compound (15 % of remaining PGE2 production). Pracoviště Ústav organické chemie a biochemie Kontakt asep@uochb.cas.cz ; Kateřina Šperková, Tel.: 232 002 584 ; Jana Procházková, Tel.: 220 183 418 Rok sběru 2022 Elektronická adresa https://doi.org/10.1002/cmdc.202100263
Počet záznamů: 1