Imidazo[1,2-c]pyrimidin-5(6H)-one as a novel core of cyclin-dependent kinase 2 inhibitors: Synthesis, activity measurement, docking, and quantum mechanical scoring

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50015476" target="_blank" >RIV/62690094:18470/18:50015476 - isvavai.cz</a>

Alternative codes found

RIV/61389030:_____/18:00492387 RIV/61388963:_____/18:00492387 RIV/61989592:15310/18:73589730

Result on the web

<a href="http://dx.doi.org/10.1002/jmr.2720" target="_blank" >http://dx.doi.org/10.1002/jmr.2720</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/jmr.2720" target="_blank" >10.1002/jmr.2720</a>

Result language

angličtina

Original language name

Imidazo[1,2-c]pyrimidin-5(6H)-one as a novel core of cyclin-dependent kinase 2 inhibitors: Synthesis, activity measurement, docking, and quantum mechanical scoring

Original language description

We report on the synthesis, activity testing, docking, and quantum mechanical scoring of novel imidazo[1,2‐c]pyrimidin‐5(6H)‐one scaffold for cyclin‐dependent kinase 2 (CDK2) inhibition. A series of 26 compounds substituted with aromatic moieties at position 8 has been tested in in vitro enzyme assays and shown to inhibit CDK2. 2D structure‐activity relationships have ascertained that small substituents at position 8 (up to the size of naphtyl or methoxyphenyl) generally lead to single‐digit micromolar IC50 values, whereas bigger substituents (substituted biphenyls) decreased the compounds&apos; activities. The binding modes of the compounds obtained using Glide docking have exhibited up to 2 hinge‐region hydrogen bonds to CDK2 and differed in the orientation of the inhibitor core and the placement of the 8‐substituents. Semiempirical quantum mechanics‐based scoring identified probable favourable binding modes, which will serve for future structure‐based design and synthetic optimization of substituents of the heterocyclic core. In summary, we have identified a novel core for CDK2 inhibition and will explore it further to increase the potencies of the compounds and also monitor selectivities against other protein kinases.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10401 - Organic chemistry

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

N - Vyzkumna aktivita podporovana z neverejnych zdroju

Publication year

2018

Confidentiality

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

Name of the periodical

Journal of molecular recognition

ISSN

0952-3499

e-ISSN

—

Volume of the periodical

31

Issue of the periodical within the volume

9

Country of publishing house

US - UNITED STATES

Number of pages

11

Pages from-to

1-11

UT code for WoS article

000441248700002

EID of the result in the Scopus database

2-s2.0-85045844397