173908-58-2Relevant articles and documents
Anti-HIV-1 NNRT agents: Acylamino Pyrryl Aryl Sulfones (APASs) as truncated analogues of tricyclic PBTDs
Silvestri, Romano,De Martino, Gabriella,Artico, Marino,La Regina, Giuseppe,Ragno, Rino,Loddo, Roberta,La Colla, Paolo,Marongiu, Maria Elena,La Colla, Massimiliano,Pani, Alessandra
, p. 195 - 218 (2007/10/03)
Pyrryl Aryl Sulfones (PASs) bearing acylamino moieties at position 2 of the benzene ring were designed as truncated analogs of pyrrolo[1,2-b][1,2,5]benzothiadiazepine 5,5-dioxides (PBTDs). Acylamino-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.
2-Sulfonyl-4-chloroanilino moiety: a potent pharmacophore for the anti-human immunodeficiency virus type 1 activity of pyrrolyl aryl sulfones.
Artico, Marino,Silvestri, Romano,Massa, Silvio,Loi, Anna G.,Corrias, Simona,et al.
, p. 522 - 530 (2007/10/03)
The synthesis and the evaluation of cytotoxicity and anti-HIV-1 activity of new aryl pyrrolyl (8) and aryl indolyl (9) sulfones are reported. Preparation of above sulfones was achieved by reacting arylsulfonyl chlorides with substituted pyrroles and indoles or by condensing sulfonamides with 2,5-dimethoxytetrahydrofuran in glacial acetic acid according to the Clauson-Kaas method. Chemical requisites relevant to the anti-HIV-1 activity of these compounds are both a 2-sulfonyl-4-chloroanilino moiety and an alkoxycarbonyl group at position 2 of the pyrrole ring. The best activity and selectivity were obtained with ethoxycarbonyl and isopropoxycarbonyl substituents. Substitutions at the amino group of the pharmacophore moiety led to inactive products (alkylation) or weakened (acylation) anti-HIV-1 activity. Among test derivatives, 16 compounds showed EC50 values ranging between 10 and 1 microM, and five (8b',d',f',h'j') showed EC50S in the sub-micromolar range. The compounds were active against HIV-1, both wild type and AZT-resistant strains, but not against HIV-2. Moreover, in enzyme assays they potently inhibited the HIV-1 recombinant reverse transcriptase, were 10 times less active against enzymes from nevirapine- and TIBO-resistant strains, and were totally inactive against the HIV-2 recombinant enzyme. Interestingly, some compounds (8r'-y') were inactive against the recombinant reverse transcriptase while being active in tissue culture.
