- Synthesis and biological evaluation of 6-substituted 5-Alkyl-2-(phenylaminocarbonylmethylthio)pyrimidin-4(3H)-ones as potent HIV-1 NNRTIs
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A series of new 5-alkyl-2-phenylaminocarbonylmethylthiopyrimidin-4(3H)-ones bearing variously substituted arylmethyl moieties at the C6 position of the pyrimidine ring were synthesized and evaluated for anti-HIV activity in MT-4 cells. Most of these new c
- Yu, Mingyan,Li, Zhenyu,Liu, Shuai,Fan, Erkang,Pannecouque, Christophe,DeClercq, Erik,Liu, Xinyong
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experimental part
p. 826 - 833
(2012/01/14)
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- Discovery of Dihydro-Alkyloxy-Benzyl-Oxopyrimidines as Promising Anti-Influenza Virus Agents
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A series of novel dihydro-alkyloxy-benzyl-oxopyrimidine derivatives were synthesized and evaluated for their activity against influenza virus in Madin-Darby canine kidney cells. Four dihydro-alkyloxy-benzyl-oxopyrimidine derivatives (4a1, 4a2, 4a3, and 4d1) showed potent activity against influenza virus. Among them, compound 4a3 was the most promising lead with broad activity against influenza A (antiviral EC50 values of 9 and 18μm for the A/H1N1 and A/H3N2 subtype, respectively) and influenza B viruses (EC50: 33μm). The antiviral mechanism of action of these dihydro-alkyloxy-benzyl-oxopyrimidine derivatives must be quite different from that of the currently approved anti-influenza virus drugs that target the viral M2 or neuraminidase proteins. The dihydro-alkyloxy-benzyl-oxopyrimidine derivatives represent a new avenue for further optimization and development of novel anti-influenza virus agents. Dihydro-alkyloxy-benzyl-oxopyrimidine (DABO) derivatives were discoveried as new anti-influenza agents. Among them, compound 4a3 was the most promising with broad activity against influenza A (A/H1N1 and A/H3N2 subtype) and influenza B virus.
- Yu, Mingyan,Liu, Ailin,Du, Guanhua,Naesens, Lieve,Vanderlinden, Evelien,De Clercq, Erik,Liu, Xinyong
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experimental part
p. 596 - 602
(2012/04/10)
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- 5-alkyl-6-benzyl-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones, a series of anti-HIV-1 agents of the dihydro-alkoxy-benzyl-oxopyrimidine family with peculiar structure - Activity relationship profile
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A series of dihydro-alkylthio-benzyl-oxopyrimidines (S-DABOs) bearing a 2-aryl-2-oxoethylsulfanyl chain at pyrimidine C2, an alkyl group at C5, and a 2,6-dichloro-, 2-chloro-6-fluoro-, and 2,6-difluoro-benzyl substitution at C6 (oxophenethyl-S-DABOs, 6-8)
- Nawrozkij, Maxim B.,Rotili, Dante,Tarantino, Domenico,Botta, Giorgia,Eremiychuk, Alexandre S.,Musmuca, Ira,Ragno, Rino,Samuele, Alberta,Zanoli, Samantha,Armand-Ugón, Mercedes,Clotet-Codina, Imma,Novakov, Ivan A.,Orlinson, Boris S.,Maga, Giovanni,Esté, José A.,Artico, Marino,Mai, Antonello
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experimental part
p. 4641 - 4652
(2009/07/04)
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- Synthesis and biological properties of novel 2-aminopyrimidin-4(3H)-ones highly potent against HIV-1 mutant strains
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Following the disclosure of dihydro-alkoxy-, dihydro-alkylthio-, and dihydro-alkylamino-benzyl-oxopyrimidines (DABOs, S-DABOs, and NH-DABOs) as potent and selective anti-HIV-1 agents belonging to the non-nucleoside reverse transcriptase inhibitor (NNRTI)
- Mai, Antonello,Artico, Marino,Rotili, Dante,Tarantino, Domenico,Clotet-Codina, Imma,Armand-Ugón, Mercedes,Ragno, Rino,Simeoni, Silvia,Sbardella, Gianluca,Nawrozkij, Maxim B.,Samuele, Alberta,Maga, Giovanni,Esté, José A.
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p. 5412 - 5424
(2008/03/13)
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- Dihydro-alkylthio-benzyl-oxopyrimidines as inhibitors of reverse transcriptase: Synthesis and rationalization of the biological data on both wild-type enzyme and relevant clinical mutants
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A series of novel S-DABO analogues, characterized by different substitution patterns at positions 2, 5, and 6 of the heterocyclic ring, were synthesized in a straightforward fashion by means of parallel synthesis and evaluated as inhibitors of human immun
- Mugnaini, Claudia,Alongi, Maddalena,Togninelli, Andrea,Gevariya, Harsukh,Brizzi, Antonella,Manetti, Fabrizio,Bernardini, Cesare,Angeli, Lucilla,Tafi, Andrea,Bellucci, Luca,Corelli, Federico,Massa, Silvio,Maga, Giovanni,Samuele, Alberta,Facchini, Marcella,Clotet-Codina, Imma,Armand-Ugón, Mercedes,Esté, José A.,Botta, Maurizio
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p. 6580 - 6595
(2008/04/12)
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- Solution-phase parallel synthesis of S-DABO analogues
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A simple and straightforward methodology for the parallel, solution-phase synthesis of a new series of S-DABO derivatives 1 and 2, bearing aromatic substituents at the C2 and C6 positions, has been developed. Starting from potassium ethyl malonates 3, thi
- Togninelli, Andrea,Carmi, Caterina,Petricci, Elena,Mugnaini, Claudia,Massa, Silvio,Corelli, Federico,Botta, Maurizio
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- Parallel solution-phase and microwave-assisted synthesis of new S-DABO derivatives endowed with subnanomolar anti-HIV-1 activity
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A simple and efficient methodology for the parallel solution-phase synthesis has been set up to obtain a series of thiouracils, in turn selectively S-benzylated under microwave irradiation to give new S-DABOs. Biological screening led to the identificatio
- Manetti, Fabrizio,Esté, José A.,Clotet-Codina, Imma,Armand-Ugón, Mercedes,Maga, Giovanni,Crespan, Emmanuele,Cancio, Reynel,Mugnaini, Claudia,Bernardini, Cesare,Togninelli, Andrea,Carmi, Caterina,Alongi, Maddalena,Petricci, Elena,Massa, Silvio,Corelli, Federico,Botta, Maurizio
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p. 8000 - 8008
(2007/10/03)
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- Does the 2-methylthiomethyl substituent really confer high anti-HIV-1 activity to S-DABOs?
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S-DABO derivatives containing the methylthiomethyl (MTM) group have been synthesized and tested for anti-HIV-1 activity in cell-based assay (MTT and p24 assays) and for their capability to target the HIV-1 reverse transcriptase in enzyme assays. Data of experiments lead to the conclusion that the introduction of a 2-MTM-thio side chain is not sufficient per se to significantly increase S-DABO's potency. Nevertheless, potent MTM-S-DABOs can be obtained by introducing a 2,6-difluorophenylmethyl moiety as a C-6 substituent.
- Sbardella, Gianluca,Mai, Antonello,Artico, Marino,Massa, Silvio,Marceddu, Tiziana,Vargiu, Laura,Marongiu, Maria Elena,La Colla, Paolo
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- 5-alkyl-2-(alkylthio)-6-(2,6-dihalophenylmethyl)-3,4-dihydropyrimidin- 4(3H)-ones: Novel potent and selective dihydro-alkoxy-benzyl-oxopyrimidine derivatives
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Molecular modeling analysis of compounds belonging to the recently published series of dihydro-alkoxy-benzyl-oxopyrimidines (DABOs), such as S- DABOs and DATNOs, gave support to the design of new 2,6-disubstituted benzyl- DABO derivatives as highly potent
- Mai, Antonello,Artico, Marino,Sbardella, Gianluca,Massa, Silvio,Novellino, Ettore,Greco, Giovanni,Loi, Anna Giulia,Tramontano, Enzo,Marongiu, Maria Elena,La Colla, Paolo
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p. 619 - 627
(2007/10/03)
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