Reaction of 1,3-phenylenediacetonitrile with the zinc organometallic reagent of ethyl 2-bromobutyrate afforded the 1,3-phenylene-bis(acetoacetate) 2 which was used as the starting material for the synthesis of 1,3-phenylene-bis[6-(2-thiouracil)] 4. Desulphurization of 4 gave the corresponding bis-uracil 6, which after silylation was N-1 alkylated with bis(allyoxy)methane using TMS-triflate as the catalyst or with chloromethyl ethyl ether to give the MKC-442 analogues 7 and 9. The amino-DABO and S-DABO derivatives 11, 12a,b and 14 were also synthesized. The anti-HIV-1 activity test showed that when MKCM42 analogues were constructed with 1,3-phenylene in all cases they were detrimental to have activity against HIV-1.

Synthesis and anti-HIV-l activity of 1,3-phenylene bis-uracil analogues of MKC-442

LODDO, ROBERTA
2007

Abstract

Reaction of 1,3-phenylenediacetonitrile with the zinc organometallic reagent of ethyl 2-bromobutyrate afforded the 1,3-phenylene-bis(acetoacetate) 2 which was used as the starting material for the synthesis of 1,3-phenylene-bis[6-(2-thiouracil)] 4. Desulphurization of 4 gave the corresponding bis-uracil 6, which after silylation was N-1 alkylated with bis(allyoxy)methane using TMS-triflate as the catalyst or with chloromethyl ethyl ether to give the MKC-442 analogues 7 and 9. The amino-DABO and S-DABO derivatives 11, 12a,b and 14 were also synthesized. The anti-HIV-1 activity test showed that when MKCM42 analogues were constructed with 1,3-phenylene in all cases they were detrimental to have activity against HIV-1.
1,3 phenylene bis[6 (2 thiouracil)]; antiretrovirus agent; emivirine; drug synthesis; uracil derivative; antiviral activity; Human immunodeficiency virus 1
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11584/15124
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