6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives as a new class of potent inhibitors of Interleukin-8-induced neutrophil chemotaxis.


:A series of 6-amino-4-oxo-1,3-diphenyl-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl derivatives was synthesized. The compounds demonstrated to be novel, potent and selective inhibitors of Interleukin-8-induced human neutrophil chemotaxis. A SAR study was performed by varying the carbonyl function at position 5 and the chain linked to the amino group at position 6 of the scaffold. All the compounds of the series displayed inhibitory activity at nano- or picomolar concentrations against Interleukin-8-driven migration and no activity against fMLP- and C5a-induced chemotaxis. The binding tests of selected compounds on CXCR1 and CXCR2 receptors were negative. The most potent derivative showed in vivo efficacy in a mouse model of Zymosan-induced peritonitis.


Bioorg Med Chem


Cesarini S,Spallarossa A,Ranise A,Bruno O,Arduino N,Bertolotto M,Dallegri F,Tognolini M,Gobbetti T,Barocelli E




Has Abstract


2009-05-15 00:00:00














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    abstract::Three series of cyclic ketone inhibitors were synthesized and evaluated against the serine protease plasmin. Peptide inhibitors that incorporated 3-oxotetrahydrofuran and 3-oxotetrahydrothiophene 1,1-dioxide groups had the highest activities. Alkylamino substituents, which were designed to bind in the S1 subsite of pl...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Xue F,Seto CT

    更新日期:2006-12-15 00:00:00

  • Design and synthesis of novel pyrimido[4,5-b]azepine derivatives as HER2/EGFR dual inhibitors.

    abstract::A novel 7,6 fused bicyclic scaffold, pyrimido[4,5-b]azepine was designed to fit into the ATP binding site of the HER2/EGFR proteins. The synthesis of this scaffold was accomplished by an intramolecular Claisen-type condensation. As the results of optimization lead us to 4-anilino and 6-functional groups, we discovered...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Kawakita Y,Seto M,Ohashi T,Tamura T,Yusa T,Miki H,Iwata H,Kamiguchi H,Tanaka T,Sogabe S,Ohta Y,Ishikawa T

    更新日期:2013-04-15 00:00:00

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    abstract::The rapid increase of resistance to drugs commonly used in the treatment of tropical diseases such as malaria and African sleeping sickness calls for the prompt development of new safe and efficacious drugs. The pathogenic protozoan parasites lack the capability of synthesising purines de novo and they take up preform...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Rodenko B,Detz RJ,Pinas VA,Lambertucci C,Brun R,Wanner MJ,Koomen GJ

    更新日期:2006-03-01 00:00:00

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    abstract::(+/-)-1-(anti-3-Hydroxy-cyclopentyl)-3-(4-methoxy-phenyl)-7-phenylamino-3,4-dihydro-1H-pyrimido[4,5-d]pyrimidin-2-one (RO4383596) is a potent and selective inhibitor of the pro-angiogenic receptor tyrosine kinases KDR, FGFR, and PDGFR. This agent has an excellent pharmacokinetic profile and is highly efficacious in ro...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: McDermott LA,Simcox M,Higgins B,Nevins T,Kolinsky K,Smith M,Yang H,Li JK,Chen Y,Ke J,Mallalieu N,Egan T,Kolis S,Railkar A,Gerber L,Luk KC

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Deschamps JD,Gautschi JT,Whitman S,Johnson TA,Gassner NC,Crews P,Holman TR

    更新日期:2007-11-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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    更新日期:2002-05-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


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    更新日期:1997-11-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Savoia D,Guerrini R,Marzola E,Salvadori S

    更新日期:2008-09-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

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    authors: Baell JB,Duggan PJ,Forsyth SA,Lewis RJ,Lok YP,Schroeder CI

    更新日期:2004-08-01 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

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    journal_title:Bioorganic & medicinal chemistry

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    authors: Biscans A,Rouanet S,Bertrand JR,Vasseur JJ,Dupouy C,Debart F

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    pub_type: 杂志文章


    authors: Lee KC,Moon BS,Lee JH,Chung KH,Katzenellenbogen JA,Chi DY

    更新日期:2003-08-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章,评审


    authors: Kazmierski W,Bifulco N,Yang H,Boone L,DeAnda F,Watson C,Kenakin T

    更新日期:2003-07-03 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Albrecht S,Defoin A,Salomon E,Tarnus C,Wetterholm A,Haeggström JZ

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    journal_title:Bioorganic & medicinal chemistry

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Hetényi C,Körtvélyesi T,Penke B

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Cui L,Thuong PT,Lee HS,Ndinteh DT,Mbafor JT,Fomum ZT,Oh WK

    更新日期:2008-12-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Hirashima A,Morimoto M,Kuwano E,Eto M

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Batista R,Humberto JL,Chiari E,de Oliveira AB

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Hieke M,Ness J,Steri R,Greiner C,Werz O,Schubert-Zsilavecz M,Weggen S,Zettl H

    更新日期:2011-09-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Martino MV,Guandalini L,Di Cesare Mannelli L,Menicatti M,Bartolucci G,Dei S,Manetti D,Teodori E,Ghelardini C,Romanelli MN

    更新日期:2017-03-15 00:00:00

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    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Wang M,Hampson DR

    更新日期:2006-03-15 00:00:00

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    abstract::The preserved fungal species Antrodia camphorata has diverse health-promoting effects and has been popularly used in East Asia as a traditional herb. We isolated a volatile compound from the culture medium of A. camphorata and identified it as gamma-dodecalactone (gamma-DDL). Cytomic screening for immune-modulating ac...

    journal_title:Bioorganic & medicinal chemistry

    pub_type: 杂志文章


    authors: Chen CJ,Vijaya Krishna R,Tsai CC,Wu WH,Chao LK,Hwang KH,Chien CM,Chang HY,Chen ST

    更新日期:2010-09-15 00:00:00