RESUMO
[structure: see text] Synthesis, structure, and reactivity toward amines of the new sulfamoylating reagent 2 are described. Compound 2 allowed sulfamoylation of amines under very mild conditions to give sulfamide derivatives in good yields.
Assuntos
Aminas/química , Di-Hidropiridinas/química , Sulfonamidas/química , Catálise , Cristalografia por Raios X , Espectroscopia de Ressonância Magnética , Conformação Molecular , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
In order to inhibit the gp 120-CD4 glycoprotein interaction, a key step of the HIV-infection, we have synthesized a series of N-acylated peptides containing sequences identified in both the viral and lymphocytic proteins, (SDFR, SDAR, RFDSAARFDS, DRADSRRS, PSKLNDRADSRRSLWD, ASTTTNYT). An hydrophobic moiety (capryloyl, palmitoyl acrylamidoundecanoyl) was introduced in the last step of interactive synthesis, in homogeneous or solid phase. The acrylogyl-containing compounds were then telomerized under UV irradiation (DPn observed: 2 to 6). The biological evaluation shown an antiviral effect in vitro for telomerized peptides containing amino diacids such as Glu and Asp.
Assuntos
Fármacos Anti-HIV/síntese química , Peptídeos/síntese química , Acilação , Sequência de Aminoácidos , Fármacos Anti-HIV/farmacologia , Imunoadesinas CD4/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo , HIV-1/efeitos dos fármacos , Humanos , Dados de Sequência Molecular , Peptídeos/farmacologia , EstereoisomerismoRESUMO
A new series of alkylating agents, 2-chloroethylnitrososulfamides (CENS), were developed on the model of 2-chloroethylnitrosoureas. Starting from chlorosulfonyl isocyanate, a four-step synthesis (carbamoylation-sulfamoylation, Mitsunobu alkylation, deprotection, and nitrosation) gives the title compounds in a 47-58% overall yield. The selection of the nitrosation site can be directed through an alternative route. The pharmacological evaluation shows a significant oncostatic activity towards both A549 and MCF7 cell lines.