2-Sulfonyl-4-chloroanilino Moiety: A Potent Pharmacophore for the Anti-Human Immunodeficiency Virus Type 1 Activity of Pyrrolyl Aryl Sulfones
Citations Over TimeTop 10% of 1996 papers
Abstract
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.
Related Papers
- → Molecular Design Based on 3D Pharmacophores. Applications to 5-HT7Receptors(2004)21 cited
- → <i>In-Silico</i> Identification of Anticancer Compounds; Ligand-Based Pharmacophore Approach against EGFR Involved in Breast Cancer(2021)6 cited
- → Applications of Pharmacophore Mapping☆(2014)3 cited
- → PHARMACOPHORE BASED SCREENING OF EPICATECHIN AGAINST COLON CANCER(2012)1 cited
- → Computational Modeling of Selective Pharmacophores at the α 1 ‐Adrenergic Receptors(2008)2 cited