Synthesis, QSAR and anti-HIV activity of new 5-benzylthio-1,3,4-oxadiazoles derived from α-amino acids.
2-(1-[(4-Chloro/methylphenylsulfonylamino)alkyl]-5-thioxo-4,5-dihydro-1,3,4-oxadiazoles (4a-e) were synthesized, in four steps, via the sulfonyl derivatives of l-amino acids (l-alanine, l-methionine and l-phenylalanine) 1a-e, the esters 2a-e, the hydrazides 3a-e and finally the cyclization to 4a-e. Alkylation of 4a-e with 1.0 mole eq. of substituted benzyl halides furnished S-benzyl derivatives 5a-t, while 1.1 mole eq. yielded major 5a-t and minor amount of 6a-d. Alternatively, treatment of 4a-e with 2.0 mole eq. of substituted benzyl halides furnished 6a-d only. The structures of 5b and 5l were further confirmed by single crystal X-ray analysis. Compounds 5a-t and 6a-d showed no selective inhibition against HIV-1 and HIV-2 replication in MT-4 cells. However, 5f and 5j-5q exhibited some inhibitory activity against both types with EC(50) values (>11.50 - >13.00 µg/mL). These results suggest that the structural modifications of these compounds might lead to the development of new antiviral agents. The quantum structure-activity relationship of these novel structural congeners is discussed.
Department of Chemistry, Quaid-I-Azam University, Islamabad, Pakistan.
Tayyaba
T
Syed
Tashfeen
T
Akhtar
Najim A
NA
Al-Masoudi
Peter G
PG
Jones
Shahid
S
Hameed
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D006678:HIV / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D010069:Oxadiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
D000998:Antiviral Agents; D010069:Oxadiazoles; D013438:Sulfhydryl Compounds; D013449:Sulfonamides