Anti-HIV-1 activity of pyrryl aryl sulfone (PAS) derivatives: synthesis and SAR studies of novel esters and amides at the position 2 of the pyrrole nucleus.
A SAR study has been performed in order to evaluate how much the ester function could be a determinant for the anti-human immunodeficiency virus type-1 activity of pyrryl aryl sulfones (PASs), a potent family of non-nucleoside reverse transcriptase (RT) inhibitors discovered in the last years. Twenty-three new esters were prepared with the aim to enhance the inhibitory potency of 4a and 4c, two PAS agents endowed with good activity (EC50 = 0.14 microM) and deprived of cytotoxicity up to >200 microM. None of test derivatives was as potent as 4a and 4c and lacked of selectivity due to their higher cytotoxicity (compounds 22-25). Antiviral activity correlate with an ester ramified chain.
Dipartimento di Studi Farmaceutici, Università di Roma "La Sapienza", Piazzale Aldo Moro 5, Rome 00185, Italy. romano.silvestri@uniroma1.it
Romano
R
Silvestri
Marino
M
Artico
Giuseppe
G
La Regina
Gabriella
G
De Martino
Massimiliano
M
La Colla
Roberta
R
Loddo
Paolo
P
La Colla
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D004952:Esters / Q000138:chemical synthesis / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology*
D000577:Amides; D019380:Anti-HIV Agents; D004952:Esters; D007202:Indicators and Reagents; D011758:Pyrroles; D013450:Sulfones