Pyrryl Aryl Sulfones (PASs) bearing acylamino moieties at position 2 of the benzene ring were designed as truncated analogs of pyrrolo[1,2b][1,2,5]benzothiadiazepine 5,5-dioxides (PBTDs). Acylarnino-PASs (APASs) were synthesized by reacting 1-(2-amino-5-chlorobenzenesulfonyl)-2-ethoxycarbonyl-1H-pyrrole with alkanoyl, aroyl or benzenesulfonyl halides in the presence of pyridine or sodium hydrogen carbonate. Some of test compounds were achieved by treating 1-(2-bromoacetylamino-5-chlorobenzenesulfonyl)-2-ethoxycarbonyl-1H-pyrrole with appropriate amines, heterocycles or sodium thiomethoxide. Reaction of 1-(2-acetylamino-5-chlorobenzenesulfonyl)-1H-pyrrole with acetyl chloride in the presence of boron trifluoride ethyl etherate or aluminum chloride afforded the related 2- and 3-acetyl-1H-pyrrole- isomers. The most potent derivatives 1-[2-(1-X-acetyl)amino-5-chlorobenzenesulfonyl]-2-ethoxycarbonyl-1H-pyrroles (X = CH3O, CH3S) were active at submicromolar concentrations, comparable with that of nevirapine. Various derivatives were as active as the related cyclic pyrrolobenzothiadiazepines (PBTDs). A binding mode investigation by molecular modeling and docking studies is reported for these novel NNRTIs. Furthermore, some information about the relation between hydrophobicity and anti-HIV activity were evaluated using calculated logP values.

Anti-HIV-1 NNRT Agents: Acylamino Pyrryl Aryl Sulfones (APASs) as Truncated Analogues of Tricyclic PBTDs / Silvestri, Romano; DE MARTINO, G.; Artico, Marino; LA REGINA, Giuseppe; Ragno, Rino; Loddo, P.; LA COLLA, P.; Marongiu, M. E.; LA COLLA, M.; Pani, A.. - In: MEDICINAL CHEMISTRY RESEARCH. - ISSN 1054-2523. - STAMPA. - 11:(2002), pp. 195-218.

Anti-HIV-1 NNRT Agents: Acylamino Pyrryl Aryl Sulfones (APASs) as Truncated Analogues of Tricyclic PBTDs.

SILVESTRI, Romano;ARTICO, Marino;LA REGINA, GIUSEPPE;RAGNO, Rino;
2002

Abstract

Pyrryl Aryl Sulfones (PASs) bearing acylamino moieties at position 2 of the benzene ring were designed as truncated analogs of pyrrolo[1,2b][1,2,5]benzothiadiazepine 5,5-dioxides (PBTDs). Acylarnino-PASs (APASs) were synthesized by reacting 1-(2-amino-5-chlorobenzenesulfonyl)-2-ethoxycarbonyl-1H-pyrrole with alkanoyl, aroyl or benzenesulfonyl halides in the presence of pyridine or sodium hydrogen carbonate. Some of test compounds were achieved by treating 1-(2-bromoacetylamino-5-chlorobenzenesulfonyl)-2-ethoxycarbonyl-1H-pyrrole with appropriate amines, heterocycles or sodium thiomethoxide. Reaction of 1-(2-acetylamino-5-chlorobenzenesulfonyl)-1H-pyrrole with acetyl chloride in the presence of boron trifluoride ethyl etherate or aluminum chloride afforded the related 2- and 3-acetyl-1H-pyrrole- isomers. The most potent derivatives 1-[2-(1-X-acetyl)amino-5-chlorobenzenesulfonyl]-2-ethoxycarbonyl-1H-pyrroles (X = CH3O, CH3S) were active at submicromolar concentrations, comparable with that of nevirapine. Various derivatives were as active as the related cyclic pyrrolobenzothiadiazepines (PBTDs). A binding mode investigation by molecular modeling and docking studies is reported for these novel NNRTIs. Furthermore, some information about the relation between hydrophobicity and anti-HIV activity were evaluated using calculated logP values.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11573/253535
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