Tetrasubstituted purines as inhibitors of CDK1

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F03%3A00001584" target="_blank" >RIV/61989592:15310/03:00001584 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Tetrasubstituted purines as inhibitors of CDK1

Popis výsledku v původním jazyce

Cyclin-dependent kinases (CDKs) have raised considerable attention because of their pivotal role in the regulation of cell division cycle. Due to their hyperactivation in a number of transformed cells, drug discovery programs direct the effort towards the identification of chemical inhibitors of CDKs as anticancer agents. In our effort to enhance the affinity of purine inhibitors to CDKs, we introduced another side chain at C8. The straightforward syntheses of 2,6,8,9-tetrasubstituted purines [1-3] generally started from previously synthesised 2,6,9-trisubstituted purines [4,5] and are described in details (see Scheme 1). The inhibitor-CDK mutual interactions between CDK2 and inhibitor were subsequently verified by molecular modelling [6]. The introduced C8 substituents, however, lowered the CDK inhibitory activity, whereas the antiproliferative activity of several derivatives remained high (Tab. 1.).

Název v anglickém jazyce

Tetrasubstituted purines as inhibitors of CDK1

Popis výsledku anglicky

Cyclin-dependent kinases (CDKs) have raised considerable attention because of their pivotal role in the regulation of cell division cycle. Due to their hyperactivation in a number of transformed cells, drug discovery programs direct the effort towards the identification of chemical inhibitors of CDKs as anticancer agents. In our effort to enhance the affinity of purine inhibitors to CDKs, we introduced another side chain at C8. The straightforward syntheses of 2,6,8,9-tetrasubstituted purines [1-3] generally started from previously synthesised 2,6,9-trisubstituted purines [4,5] and are described in details (see Scheme 1). The inhibitor-CDK mutual interactions between CDK2 and inhibitor were subsequently verified by molecular modelling [6]. The introduced C8 substituents, however, lowered the CDK inhibitory activity, whereas the antiproliferative activity of several derivatives remained high (Tab. 1.).

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

ED - Fyziologie

OECD FORD obor

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Projekt

<a href="/cs/project/GA301%2F02%2F0475" target="_blank" >GA301/02/0475: Protinádorové a antimitotické látky na bázi purinových inhibitorů cyklin-dependentních kinas</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2003

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Cellular & Molecular Biology Letters

ISSN

1425-8153

e-ISSN

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Svazek periodika

8

Číslo periodika v rámci svazku

8

Stát vydavatele periodika

PL - Polská republika

Počet stran výsledku

1

Strana od-do

596

Kód UT WoS článku

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EID výsledku v databázi Scopus

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