Amino acid derivatives, part 4: synthesis and anti-HIV activity of new naphthalene derivatives.

A new series of 2-(naphthalen-2-yloxy)-N-[(aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-3-yl)methyl] acetamides 5a-f was synthesized from naphthalene-derived glycine derivative 2 via the hydrazinoacetamide analogs 4a-f. Alternatively, treatment of 4a with H(2)SO(4) afforded 2-(naphthalen-2-yloxy)-N-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)methyl) acetamide 6a. Alkylation or sulphonylation of 5a afforded the S-alkylated derivatives 7 and 8, respectively. Interestingly, treatment of 3 with methoxide ion gave the triazine derivative 9. The synthesized compounds have been screened for their inhibitory activity against HIV-1 and HIV-2 in MT-4 cells. However, 7 was found to be the potent inhibitor in vitro for the replication of HIV-1 (EC(50 )= 0.20 microg/mL), suggesting a new lead in the development of an antiviral agent.