Targeting Delavirdine/Atevirdine Resistant HIV-1:  Identification of (Alkylamino)piperidine-Containing Bis(heteroaryl)piperazines as Broad Spectrum HIV-1 Reverse Transcriptase Inhibitors

Dl, Romero; Ra, Olmsted; Tj, Poel; Ra, Morge; Biles, C.; Bj, Keiser; La, Kopta; Jm, Friis; Jd, Hosley; Kj, Stefanski; Dg, Wishka; Db, Evans; Morris, Joel; Rg, Stehle; Sk, Sharma; Yagi, Yoshihiko; Rl, Voorman; Wj, Adams; Wg, Tarpley; Rc, Thomas

doi:10.1021/jm960158n

Cited by 63 publications

(63 citation statements)

References 38 publications

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“…In cell culture efavirenz selects for a double mutation (L100I plus L103A) following 10 serial passages at increasing concentrations (Young et al, 1995a). However, no single RT substitution has yielded a mutant Romero et al (1996). (Table 8).…”

Section: Benzoxazinonesmentioning

confidence: 99%

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Non-Nucleoside Reverse Transcriptase Inhibitors: The NNRTI Boom

Pedersen

1999

Antivir Chem Chemother

124

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Section: Benzoxazinonesmentioning

confidence: 99%

“…HEPT was synthesized as an acyclonucleoside and was expected to be a member of the nucleoside class of RT inhibitors, which act as competitive inhibitors by mimicking the natural substrate for the enzyme (Tantillo et al, Romero et al (1996). 1994).…”

Section: Hept Derivativesmentioning

confidence: 99%

Non-Nucleoside Reverse Transcriptase Inhibitors: The NNRTI Boom

Pedersen

1999

Antivir Chem Chemother

124

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“…27 where several drug resistant mutant strains were used together. The QSAR models built using the data sets from these sources have poor accuracy and predictivity.…”

Section: Results Based On Modeling Sets From Chemblmentioning

confidence: 99%

QSAR Modeling Using Large-Scale Databases: Case Study for HIV-1 Reverse Transcriptase Inhibitors

Tarasova

Urusova

Филимонов

et al. 2015

J. Chem. Inf. Model.

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Large-scale databases are important sources of training sets for various QSAR modeling approaches. Generally, these databases contain information extracted from different sources. This variety of sources can produce inconsistency in the data, defined as sometimes widely diverging activity results for the same compound against the same target. Because such inconsistency can reduce the accuracy of predictive models built from these data, we are addressing the question of how best to use data from publicly and commercially accessible databases to create accurate and predictive QSAR models. We investigate the suitability of commercially and publicly available databases to QSAR modeling of antiviral activity (HIV-1 reverse transcriptase (RT) inhibition). We present several methods for the creation of modeling (i.e., training and test) sets from two, either commercially or freely available, databases: Thomson Reuters Integrity and ChEMBL. We found that the typical predictivities of QSAR models obtained using these different modeling set compilation methods differ significantly from each other. The best results were obtained using training sets compiled for compounds tested using only one method and material (i.e., a specific type of biological assay). Compound sets aggregated by target only typically yielded poorly predictive models. We discuss the possibility of "mix-and-matching" assay data across aggregating databases such as ChEMBL and Integrity and their current severe limitations for this purpose. One of them is the general lack of complete and semantic/computer-parsable descriptions of assay methodology carried by these databases that would allow one to determine mix-and-matchability of result sets at the assay level.

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“…An indole-containing compound, delavirdine ( Fig. 1), was shown to be a HIV-1 reverse transcriptase inhibitor and approved as a commercial anti-HIV drug named, Rescriptor ® (Romero et al, 1996). N-Alkyl-substituted indolocarbazoles were reported to be potent inhibitors of the human cytomegalovirus in nM concentrations (Slater et al, 2001).…”

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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Targeting Delavirdine/Atevirdine Resistant HIV-1: Identification of (Alkylamino)piperidine-Containing Bis(heteroaryl)piperazines as Broad Spectrum HIV-1 Reverse Transcriptase Inhibitors

Cited by 63 publications

References 38 publications

Non-Nucleoside Reverse Transcriptase Inhibitors: The NNRTI Boom

Non-Nucleoside Reverse Transcriptase Inhibitors: The NNRTI Boom

QSAR Modeling Using Large-Scale Databases: Case Study for HIV-1 Reverse Transcriptase Inhibitors

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

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