Synthesis and anti-human immunodeficiency virus activity of substituted (o,o-difluorophenyl)-linked-pyrimidines as potent non‐nucleoside reverse transcriptase inhibitors

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F19%3A00518189" target="_blank" >RIV/61388963:_____/19:00518189 - isvavai.cz</a>

Result on the web

<a href="https://journals.sagepub.com/doi/full/10.1177/2040206619826265" target="_blank" >https://journals.sagepub.com/doi/full/10.1177/2040206619826265</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1177/2040206619826265" target="_blank" >10.1177/2040206619826265</a>

Result language

angličtina

Original language name

Synthesis and anti-human immunodeficiency virus activity of substituted (o,o-difluorophenyl)-linked-pyrimidines as potent non‐nucleoside reverse transcriptase inhibitors

Original language description

With the worldwide number of human immunodeficiency virus positive patients stagnant and the increasing emergence of viral strains resistant to current treatment, the development of novel anti-human immunodeficiency virus drug candidates is a perpetual quest of medicinal chemists. Herein, we report a novel group of diarylpyrimidines, non-nucleoside reverse transcriptase inhibitors, which represents an important class of current anti-human immunodeficiency virus therapy. Series of diarylpyrimidines containing o,o-difluorophenyl (A-arm), 4-cyanophenylamino (B-arm), and a small substituent (e.g. NH2 , OMe) at positions 2, 4, and 6 of the pyrimidine ring were prepared. The A-arm was modified in the para position (F or OMe) and linked to the central pyrimidine core with a variable spacer (CO, O, NH). Antiviral activities of 20 compounds were measured against wild type human immunodeficiency virus-1 and mutant reverse transcriptase strains (K103N, Y181C) using a cytoprotection assay. To the most promising structural motives belong the o,o-difluoro-p-methoxy A-arm in position 4, and the amino group in position 6 of pyrimidine. Single digit nanomolar activities with no significant toxicity (CC50 > 17,000 nM) were found for compounds 35 (EC50 = 2 nM), 37 (EC50 = 3 nM), and 13 (EC50 = 4 nM) having O, NH, and CO linkers, respectively.

Czech name

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Czech description

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Type

J_SC - Article in a specialist periodical, which is included in the SCOPUS database

CEP classification

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OECD FORD branch

10401 - Organic chemistry

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

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

Name of the periodical

Antiviral Chemistry and Chemotherapy

ISSN

0956-3202

e-ISSN

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Volume of the periodical

27

Issue of the periodical within the volume

Feb 6

Country of publishing house

GB - UNITED KINGDOM

Number of pages

18

Pages from-to

1-18

UT code for WoS article

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EID of the result in the Scopus database

2-s2.0-85061635329