As a part of our extensive structure-activity relationship study of anti-inflammatory heterocycles, a novel series of 67 polysubstituted 2-aminopyrimidines was prepared bearing one (at the C-4 position of the pyrimidine ring) or two (in the C-4 and C-6 positions) (hetero)aryl substituents attached directly through the C-C bond. The key synthetic steps involved either Suzuki-Miyaura or Stille cross-coupling reactions carried out on easily available 4,6-dichloropyrimidines. All prepared compounds, except one, were able to inhibit immune-activated production of nitric oxide (NO) significantly. Moreover, several compounds were found to be low micromolar dual inhibitors of NO and prostaglandin E2 (PGE2) production. Although the exact mode of action of the prepared compounds remains to be elucidated, non-toxic dual inhibitors of NO and PGE2 production may have great therapeutic benefit in treatment of various inflammation diseases and deserve further preclinical evaluation.

Institute of Experimental Medicine Academy of Sciences of the Czech Republic Vídeňská 1083 142 20 Prague 4 Czech Republic

Institute of Organic Chemistry and Biochemistry The Czech Academy of Sciences Flemingovo Nám 2 166 10 Prague 6 Czech Republic

000      

00000naa a2200000 a 4500

001      

bmc18033907

003      

CZ-PrNML

005      

20181029112045.0

007      

ta

008      

181008s2017 xxu f 000 0|eng||

009      

AR

024    7_

$a 10.1016/j.niox.2017.05.001 $2 doi

035    __

$a (PubMed)28483702

040    __

$a ABA008 $b cze $d ABA008 $e AACR2

041    0_

$a eng

044    __

$a xxu

100    1_

$a Kolman, Viktor $u Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo Nám. 2, 166 10 Prague 6, Czech Republic.

245    10

$a Polysubstituted 4,6-bis(hetero)arylpyrimidines as dual inhibitors of nitric oxide and prostaglandin E2 production / $c V. Kolman, P. Jansa, F. Kalčic, Z. Janeba, Z. Zídek,

520    9_

$a As a part of our extensive structure-activity relationship study of anti-inflammatory heterocycles, a novel series of 67 polysubstituted 2-aminopyrimidines was prepared bearing one (at the C-4 position of the pyrimidine ring) or two (in the C-4 and C-6 positions) (hetero)aryl substituents attached directly through the C-C bond. The key synthetic steps involved either Suzuki-Miyaura or Stille cross-coupling reactions carried out on easily available 4,6-dichloropyrimidines. All prepared compounds, except one, were able to inhibit immune-activated production of nitric oxide (NO) significantly. Moreover, several compounds were found to be low micromolar dual inhibitors of NO and prostaglandin E2 (PGE2) production. Although the exact mode of action of the prepared compounds remains to be elucidated, non-toxic dual inhibitors of NO and PGE2 production may have great therapeutic benefit in treatment of various inflammation diseases and deserve further preclinical evaluation.

650    _2

$a zvířata $7 D000818

650    _2

$a dinoproston $x antagonisté a inhibitory $7 D015232

650    _2

$a ženské pohlaví $7 D005260

650    _2

$a myši inbrední C57BL $7 D008810

650    _2

$a molekulární struktura $7 D015394

650    _2

$a oxid dusnatý $x antagonisté a inhibitory $7 D009569

650    _2

$a pyrimidiny $x chemická syntéza $x farmakologie $x toxicita $7 D011743

655    _2

$a časopisecké články $7 D016428

700    1_

$a Jansa, Petr $u Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo Nám. 2, 166 10 Prague 6, Czech Republic.

700    1_

$a Kalčic, Filip $u Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo Nám. 2, 166 10 Prague 6, Czech Republic.

700    1_

$a Janeba, Zlatko $u Institute of Organic Chemistry and Biochemistry, The Czech Academy of Sciences, Flemingovo Nám. 2, 166 10 Prague 6, Czech Republic. Electronic address: janeba@uochb.cas.cz.

700    1_

$a Zídek, Zdeněk $u Institute of Experimental Medicine, Academy of Sciences of the Czech Republic, Vídeňská 1083, 142 20 Prague 4, Czech Republic. Electronic address: zidekz@biomed.cas.cz.

773    0_

$w MED00004882 $t Nitric oxide biology and chemistry $x 1089-8611 $g Roč. 67, č. - (2017), s. 53-57

856    41

$u https://pubmed.ncbi.nlm.nih.gov/28483702 $y Pubmed

910    __

$a ABA008 $b sig $c sign $y a $z 0

990    __

$a 20181008 $b ABA008

991    __

$a 20181029112600 $b ABA008

999    __

$a ok $b bmc $g 1339650 $s 1030901

BAS    __

$a 3

BAS    __

$a PreBMC

BMC    __

$a 2017 $b 67 $c - $d 53-57 $e 20170505 $i 1089-8611 $m Nitric oxide $n Nitric oxide $x MED00004882

LZP    __

$a Pubmed-20181008