5-Chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase

Williams, Theresa M.; Ciccarone, Terrence M.; MacTough, Suzanne C.; Rooney, C. S.; Balani, Suresh K.; Condra, Jon H.; Emini, Emilio A.; Goldman, Mark E.; Greenlee, William J.

doi:10.1021/jm00061a022

Cited by 258 publications

(85 citation statements)

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“…5 Among them, L-737,126 (4), a benzenesulfonylindolcarboxamide endowed with potent antiviral activity and high selectivity, has been developed by Merck A. G. Despite its highest activity, L-737,126 was not suitable for clinical trials, because of its low bioavailability rising from its scarce solubility in water. 13 Merck Research Laboratories attempted to overcome this problem by replacing the 2-carboxamide function with some heterocycles (for example compounds 5a-5c), but the new compounds increased only marginally the water solubility of 4. 14 Nevertheless, some of them were found to be active against resistant mutants, with compound 5a being 11 times more active than 4 against the K103N mutant (Chart 2).…”

Section: Introductionmentioning

confidence: 99%

Docking and 3-D QSAR Studies on Indolyl Aryl Sulfones. Binding Mode Exploration at the HIV-1 Reverse Transcriptase Non-Nucleoside Binding Site and Design of Highly Active N-(2-Hydroxyethyl)carboxamide and N-(2-Hydroxyethyl)carbohydrazide Derivatives

et al. 2004

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Three-dimensional quantitative structure-activity relationship (3-D QSAR) studies and docking simulations were developed on indolyl aryl sulfones (IASs), a class of novel HIV-1 non-nucleoside reverse transcriptase (RT) inhibitors (Silvestri, et al. J. Med. Chem. 2003, 46, 2482-2493) highly active against wild type and some clinically relevant resistant strains (Y181C, the double mutant K103N-Y181C, and the K103R-V179D-P225H strain, highly resistant to efavirenz). Predictive 3-D QSAR models using the combination of GRID and GOLPE programs were obtained using a receptor-based alignment by means of docking IASs into the non-nucleoside binding site (NNBS) of RT. The derived 3-D QSAR models showed conventional correlation (r(2)) and cross-validated (q(2)) coefficients values ranging from 0.79 to 0.93 and from 0.59 to 0.84, respectively. All described models were validated by an external test set compiled from previously reported pyrryl aryl sulfones (Artico, et al. J. Med. Chem. 1996, 39, 522-530). The most predictive 3-D QSAR model was then used to predict the activity of novel untested IASs. The synthesis of six designed derivatives (prediction set) allowed disclosure of new IASs endowed with high anti-HIV-1 activities.

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Section: Introductionmentioning

confidence: 99%

Docking and 3-D QSAR Studies on Indolyl Aryl Sulfones. Binding Mode Exploration at the HIV-1 Reverse Transcriptase Non-Nucleoside Binding Site and Design of Highly Active N-(2-Hydroxyethyl)carboxamide and N-(2-Hydroxyethyl)carbohydrazide Derivatives

et al. 2004

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“…Some of the indole alkaloids extracted from plants possess interesting cytotoxic, antitumour or antiparasitic properties [1,2]. Pyrido [1,2-a] indole derivatives have been identified as potent inhibitors of human immunodeficiency virus type-1 [3], and 5-chloro-3-(phenylsulfonyl) indole-2-carboxamide is reported to be a highly potent non-nucleoside inhibitor of HIV-1 reverse transcriptase [4]. The interaction of phenylsulfonylindole with calf thymus DNA has also been studied by spectroscopic methods [5].…”

Section: Introductionmentioning

confidence: 99%

Experimental and Theoretical Spectroscopic Analysis on N-((1-(phenylsulfonyl)- 1H-indol-3-Yl)methyl)acetamide

Srinivasaraghavan¹,

Seshadri²,

Gnanasambandan³

et al. 2017

Pharm Anal Acta

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In this work, The structural characteristics and vibrational spectroscopic analysis were carried out by quantum chemical methods with the hybrid exchange-correlation functional B3LYP using 6-31G (d, p) and 6-311++G (d, p) basis sets in order to investigate the fundamental modes of vibrational analysis and electronic properties of phenyl substituted compound N-((1-(phenylsulfonyl)-1H-indol-3-yl)methyl)acetamide. Density Functional Theory (DFT) method, using B3LYP functional, with 6-31G (d, p) and 6-311++G (d, p) basis sets, which in turn creates a platform to study the structure of the chosen compound. The experimentally obtained FTIR and FT Raman spectrum supports the results of theoretically observed ones. Detailed interpretations of the experimental spectra of the molecule along with the theoretical ones are reported based on Potential Energy Distribution (PED).The total dipole moment, static total and anisotropy of polarisability and static first hyperpolarisability values were calculated. The FMOs, molecular electrostatic potential, global reactivity descriptors were also calculated and discussed. Molecular electrostatic potential and frontier molecular orbitals were constructed to understand the electronic properties. The intramolecular contacts are interpreted using Natural Bond Orbital (NBO) analysis to ascertain the charge distribution. The thermodynamic properties at different temperatures were calculated revealing the correlations between standard heat capacities, entropy and enthalpy changes with temperatures.

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“…Among them, 5-chloro-3-(phenylsulfonyl)indole-2-carboxamide derivatives were found to be HIV-1 reverse transcriptase inhibitors with IC 50 values in the nM range (Williams et al, 1993). An indole-containing compound, delavirdine ( Fig.…”

Section: Introductionmentioning

confidence: 99%

A Study of 3-Substituted Benzylidene-1,3-dihydro-indoline Derivatives as Antimicrobial and Antiviral Agents

Ölgen

Özkan

2009

Zeitschrift Für Naturforschung C

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3-Substituted benzylidene-1,3-dihydro-indoline derivatives were tested for their in vitro antibacterial activity against the Gram-negative bacteria Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, and the Gram-positive bacteria Bacillus subtilis, Staphylococcus aureus, and for their their in vitro antifungal activity against Candida krusei and Candida albicans. The minimum inhibitory concentration (MIC) values were determined by the 2-fold serial dilution technique in Mueller Hinton broth and Sabouraud dextrose agar using antibacterial and antifungal assays, respectively. For comparison of the antimicrobial activity, rifampicin, ampicillin trihydrate, gentamicin sulfate, and ofl oxacin were used as reference antibacterial agents, and fl uconazole and amphotericin B were employed as reference antifungal agents. The most active compound 10 showed notable inhibition against Bacillus subtilis, Staphylococcus aureus, and Candida krusei. Compounds 1 and 6 were found slightly effective against Klebsiella pneumoniae and Escherichia coli. In addition, compounds 13 and 14 showed inhibition against Bacillus subtilis and Staphylococcus aureus. Indole derivatives were also tested in vitro for replication of the HepAD38 cell line and compared with lamivudine (3TC, L-2′,3′-dideoxy-3′-thiacytidine). The IC 50 values of the compounds were found to be >1000 μM against HBV except for compound 13 which exhibited activity with an IC 50 value of 500 μM.

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5-Chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase

Cited by 258 publications

References 5 publications

Docking and 3-D QSAR Studies on Indolyl Aryl Sulfones. Binding Mode Exploration at the HIV-1 Reverse Transcriptase Non-Nucleoside Binding Site and Design of Highly Active N-(2-Hydroxyethyl)carboxamide and N-(2-Hydroxyethyl)carbohydrazide Derivatives

Docking and 3-D QSAR Studies on Indolyl Aryl Sulfones. Binding Mode Exploration at the HIV-1 Reverse Transcriptase Non-Nucleoside Binding Site and Design of Highly Active N-(2-Hydroxyethyl)carboxamide and N-(2-Hydroxyethyl)carbohydrazide Derivatives

Experimental and Theoretical Spectroscopic Analysis on N-((1-(phenylsulfonyl)- 1H-indol-3-Yl)methyl)acetamide

A Study of 3-Substituted Benzylidene-1,3-dihydro-indoline Derivatives as Antimicrobial and Antiviral Agents

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