Page last updated: 2024-12-10

r-82913

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Description

R-82913: antiviral target on reverse transcriptase of HIV-1 [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID3000237
CHEMBL ID293498
SCHEMBL ID1077005
MeSH IDM0184793

Synonyms (47)

Synonym
bdbm1868
(11s)-6-chloro-11-methyl-10-(3-methylbut-2-en-1-yl)-1,3,10-triazatricyclo[6.4.1.0^{4,13}]trideca-4,6,8(13)-triene-2-thione
(+)-(5s)-4,5,6,7-tetrahydro-9-chloro 5-methyl-6-(3-methyl-2-butenyl)imidazo[4,5,1-jk] [ 1,4] benzodiazepine 2(1m-thione
nsc-637653
tibo r82913
s-(+)-4,5,6,7-tetrahydro-9-chloro-5-methyl-6-(3-methyl-2-butenyl)-imidazo[4,5,1-jk][1,4]-benzodiazepine-2(1h)-thione
nsc637653
9-cl-tibo
r82913
r 82913
r-82913
126347-69-1
4-chloro-8-methyl-7-(3-methyl-but-2-enyl)-6,7,8,9-tetrahydro-2h-2,7,9a-triaza-benzo[cd]azulene-1-thione
tb9 ,
1TVR
1REV
9-chloro-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)imidazo(4,5,1-jk)(1,4)benzodiazepine-2-(1h)-thione
9-cmbib
4,5,6,7-tetrahydro-9-chloro-5-methyl-6-(3-methyl-2-butenyl)imidazo(4,5,1-jk)(1,4)benzodiazepin-2-(1h)-thione
imidazo(4,5,1-jk)(1,4)benzodiazepine-2(1h)-thione, 9-chloro-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)-, (s)-
nsc 637653
DB08598
CHEMBL293498 ,
(s)-7-allyl-4-chloro-8-methyl-6,7,8,9-tetrahydro-2h-2,7,9a-triaza-benzo[cd]azulene-1-thione
14-(1-ethynyl)-9,15-dimethyl-(1s,9r,10r,11s,14r)-tetracyclo[8.7.0.02,7.011,15]heptadec-2(7)-en-14-ol
(s)-4-chloro-8-methyl-7-(3-methyl-but-2-enyl)-6,7,8,9-tetrahydro-2h-2,7,9a-triaza-benzo[cd]azulene-1-thione
9-chloro-5-methyl-6-(3-methyl-but-2-enyl)-1,5,6,7-tetrahydro-benzo[e][1,4]diazepine-2-thione
(5s)-9-chloro-5-methyl-6-(3-methylbut-2-enyl)-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepine-2(1h)-thione
4-chloro-8-methyl-7-(3-methyl-but-2-enyl)-6,7,8,9-tetrahydro-2h-2,7,9a-triaza-benzo[cd]azulene-1-thione(9-cl tibo)
4-chloro-8-methyl-7-(3-methyl-but-1-enyl)-6,7,8,9-tetrahydro-2h-2,7,9a-triaza-benzo[cd]azulene-1-thione
7-allyl-9-chloro-8-methyl-6,7,8,9-tetrahydro-2h-2,7,9a-triaza-benzo[cd]azulen-1-one
bdbm50279762
(7r,8s)-4-chloro-8-methyl-7-(3-methyl-but-2-enyl)-6,7,8,9-tetrahydro-2h-2,7,9a-triaza-benzo[cd]azulene-1-thione
4foi87e52p ,
unii-4foi87e52p
r 82913, (r)-isomer
tibo-r-82913
9cl-tibo
imidazo(4,5,1-jk)(1,4)benzodiazepine-2(1h)-thione, 9-chloro-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-buten-1-yl)-, (5s)-
SCHEMBL1077005
DTXSID30155158
(11s)-6-chloro-11-methyl-10-(3-methylbut-2-enyl)-1,3,10-triazatricyclo[6.4.1.04,13]trideca-4,6,8(13)-triene-2-thione
(5s)-9-chloro-5-methyl-6-(3-methylbut-2-en-1-yl)-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepine-2(1h)-thione
(s)-4-chloro-8-methyl-7-(3-methylbut-2-en-1-yl)-6,7,8,9-tetrahydro-2,7,9a-triazabenzo[cd]azulene-1(2h)-thione
Q27097798
tibo-r 82913
AKOS040749267

Research Excerpts

Compound-Compound Interactions

ExcerptReferenceRelevance
" Additive to slightly synergistic results were obtained in combinations with ddI and phosphonoformic acid whereas additive to antagonistic activity was detected in combination with dextran sulfate."( Differential antiviral activity of two TIBO derivatives against the human immunodeficiency and murine leukemia viruses alone and in combination with other anti-HIV agents.
Allen, LB; Buckheit, RW; Chirigos, MA; Germany-Decker, J; Hollingshead, MG; Janssen, PA; Shannon, WM, 1993
)
0.29

Bioavailability

ExcerptReferenceRelevance
" Oral bioavailability of TIBO appears to be low and is not improved by the adjunction of probenecid."( Pharmacokinetics of R 82913 in AIDS patients: a phase I dose-finding study of oral administration compared with intravenous infusion.
Cauwenbergh, GF; Clumeck, N; De Wit, S; Hermans, P; O'Doherty, E; Sommereijns, B; van de Velde, V; Westenborghs, R, 1992
)
0.28
" Good oral bioavailability was observed in rhesus monkeys upon oral dosing of 1 as a suspension in methocel."( 5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase.
Balani, SK; Ciccarone, TM; Condra, JH; Emini, EA; Goldman, ME; Greenlee, WJ; Kauffman, LR; MacTough, SC; Rooney, CS; Williams, TM, 1993
)
0.29

Dosage Studied

ExcerptRelevanceReference
" Good oral bioavailability was observed in rhesus monkeys upon oral dosing of 1 as a suspension in methocel."( 5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase.
Balani, SK; Ciccarone, TM; Condra, JH; Emini, EA; Goldman, ME; Greenlee, WJ; Kauffman, LR; MacTough, SC; Rooney, CS; Williams, TM, 1993
)
0.29
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (8)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, Hiv-1 Reverse TranscriptaseHuman immunodeficiency virus 1Ki0.03300.03300.03300.0330AID977610
Chain B, Hiv-1 Reverse TranscriptaseHuman immunodeficiency virus 1Ki0.03300.03300.03300.0330AID977610
Chain A, Reverse TranscriptaseHuman immunodeficiency virus type 1 (CLONE 12)IC50 (µMol)0.03300.00460.01880.0330AID977608
Chain A, Reverse TranscriptaseHuman immunodeficiency virus 1IC50 (µMol)0.03300.00460.01880.0330AID977608
Chain B, Reverse TranscriptaseHuman immunodeficiency virus 1IC50 (µMol)0.03300.00460.01880.0330AID977608
Gag-Pol polyproteinHIV-1 M:B_HXB2RIC50 (µMol)13.24730.00060.91418.3200AID1795346; AID1795367; AID1795381
Reverse transcriptase/RNaseH Human immunodeficiency virus 1IC50 (µMol)11.63330.00011.076810.0000AID197784; AID197795; AID198252
Protease Human immunodeficiency virus 1IC50 (µMol)15.71030.00010.22487.3200AID200169; AID200170; AID200171
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Reverse transcriptase/RNaseH Human immunodeficiency virus 1EC50 (µMol)1.89770.00040.61539.7000AID199989; AID199991; AID199996
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Reverse transcriptase/RNaseH Human immunodeficiency virus 1Activity0.04200.00091.30738.0000AID199980; AID199983
Reverse transcriptase/RNaseH Human immunodeficiency virus 1ED500.25000.00020.99359.8000AID105522
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (2)

Processvia Protein(s)Taxonomy
viral life cycleGag-Pol polyproteinHIV-1 M:B_HXB2R
establishment of integrated proviral latencyGag-Pol polyproteinHIV-1 M:B_HXB2R
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (2)

Processvia Protein(s)Taxonomy
peptidase activityGag-Pol polyproteinHIV-1 M:B_HXB2R
integrase activityGag-Pol polyproteinHIV-1 M:B_HXB2R
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (33)

Assay IDTitleYearJournalArticle
AID106239Concentration required for 50% protection of MT-4 cells against the cytopathic effect of HIV-11995Journal of medicinal chemistry, Mar-03, Volume: 38, Issue:5
Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo-[4,5,1-jk][1,4]benzodiazepin- 2(1H)-one (TlBO) derivatives. 4.
AID45185Cytotoxicity against wild type HIV-1-IIIB strain infected CEMSS cells.1995Journal of medicinal chemistry, Nov-10, Volume: 38, Issue:23
A new series of pyridinone derivatives as potent non-nucleoside human immunodeficiency virus type 1 specific reverse transcriptase inhibitors.
AID199991Effective concentration required against L100I mutant HIV-1 reverse transcriptase2001Bioorganic & medicinal chemistry letters, Nov-05, Volume: 11, Issue:21
Antiviral drug design: computational analyses of the effects of the L100I mutation for HIV-RT on the binding of NNRTIs.
AID199989Effective concentration against HIV-1 reverse transcriptase1999Journal of medicinal chemistry, Mar-11, Volume: 42, Issue:5
Prediction of the binding free energies of new TIBO-like HIV-1 reverse transcriptase inhibitors using a combination of PROFEC, PB/SA, CMC/MD, and free energy calculations.
AID197795Inhibition of HIV-1 reverse transcriptase using rCdG as template and dGTP as substrate1995Journal of medicinal chemistry, Dec-08, Volume: 38, Issue:25
Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs.
AID232755Selectivity index is the ratio of cytotoxicity in Molt-4 cells and anti-HIV- IC501993Journal of medicinal chemistry, Dec-24, Volume: 36, Issue:26
The inophyllums, novel inhibitors of HIV-1 reverse transcriptase isolated from the Malaysian tree, Calophyllum inophyllum Linn.
AID81589Anti-HIV activity against HIV-1 in Molt-4 cells using 7-day infective assay1993Journal of medicinal chemistry, Dec-24, Volume: 36, Issue:26
The inophyllums, novel inhibitors of HIV-1 reverse transcriptase isolated from the Malaysian tree, Calophyllum inophyllum Linn.
AID246198Effective concentration of the compound to inhibit HIV-1 replication in HIV-infected MT-4 cells2005Journal of medicinal chemistry, Mar-24, Volume: 48, Issue:6
From 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk](1,4)benzodiazepin-2(1H)-one (TIBO) to etravirine (TMC125): fifteen years of research on non-nucleoside inhibitors of HIV-1 reverse transcriptase.
AID200169Inhibition of HIV-1 RT using rC-dG as template1993Journal of medicinal chemistry, Apr-30, Volume: 36, Issue:9
5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase.
AID83404Tested for inhibitory concentration on HIV-I nevirapine resistant strain.2000Journal of medicinal chemistry, Oct-19, Volume: 43, Issue:21
Synthesis and antiviral activity of 4-benzyl pyridinone derivatives as potent and selective non-nucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitors.
AID477349Antiviral activity against HIV1 infected in human MT4 cells assessed as protection against virus-induced cytopathic effect2010European journal of medicinal chemistry, Apr, Volume: 45, Issue:4
Support vector machines: development of QSAR models for predicting anti-HIV-1 activity of TIBO derivatives.
AID198252Inhibitory concentration against HIV-1 reverse transcriptase in scintillation proximity assay1993Journal of medicinal chemistry, Dec-24, Volume: 36, Issue:26
The inophyllums, novel inhibitors of HIV-1 reverse transcriptase isolated from the Malaysian tree, Calophyllum inophyllum Linn.
AID104315Ability to block replication of HIV-1 virus in mock infected MT-4 cells1991Journal of medicinal chemistry, Nov, Volume: 34, Issue:11
Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-on e (TIBO) derivatives. 2.
AID125356Tested for cytotoxicity in Molt-4 cells by XTT assay1993Journal of medicinal chemistry, Dec-24, Volume: 36, Issue:26
The inophyllums, novel inhibitors of HIV-1 reverse transcriptase isolated from the Malaysian tree, Calophyllum inophyllum Linn.
AID199996Effective concentration required against wild type HIV-1 reverse transcriptase2001Bioorganic & medicinal chemistry letters, Nov-05, Volume: 11, Issue:21
Antiviral drug design: computational analyses of the effects of the L100I mutation for HIV-RT on the binding of NNRTIs.
AID199981Inhibition of HIV-1 reverse transcriptase; + = active1994Journal of medicinal chemistry, Aug-05, Volume: 37, Issue:16
HIV-1 reverse transcriptase inhibitor design using artificial neural networks.
AID199980Inhibitory activity against human immunodeficiency virus type 1 reverse transcriptase (HIV-1 RT)2002Journal of medicinal chemistry, Jul-04, Volume: 45, Issue:14
Prediction of activity for nonnucleoside inhibitors with HIV-1 reverse transcriptase based on Monte Carlo simulations.
AID200171Inhibition single mutant of HIV-1 RT (Y181C)1993Journal of medicinal chemistry, Apr-30, Volume: 36, Issue:9
5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase.
AID200170Inhibition single mutant of HIV-1 RT (K103 N)1993Journal of medicinal chemistry, Apr-30, Volume: 36, Issue:9
5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase.
AID197784Inhibition of HIV-1 reverse transcriptase.1998Journal of medicinal chemistry, Dec-17, Volume: 41, Issue:26
Prediction of binding affinities for TIBO inhibitors of HIV-1 reverse transcriptase using Monte Carlo simulations in a linear response method.
AID226235Fold resistance (L100I/ WT) was determined2001Bioorganic & medicinal chemistry letters, Nov-05, Volume: 11, Issue:21
Antiviral drug design: computational analyses of the effects of the L100I mutation for HIV-RT on the binding of NNRTIs.
AID104944Concentration which reduced the viability of the HIV-1 infected MT-4 cells to 50% compared to untreated control cells1995Journal of medicinal chemistry, Dec-08, Volume: 38, Issue:25
Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs.
AID106775Inhibition of cell culture in MT-4 cells1993Journal of medicinal chemistry, Apr-30, Volume: 36, Issue:9
5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase.
AID477005Inhibition of HIV reverse transcriptase2010European journal of medicinal chemistry, Apr, Volume: 45, Issue:4
MIA-QSAR coupled to principal component analysis-adaptive neuro-fuzzy inference systems (PCA-ANFIS) for the modeling of the anti-HIV reverse transcriptase activities of TIBO derivatives.
AID83403Tested for cytotoxic concentration on HIV-I nevirapine resistant strain.2000Journal of medicinal chemistry, Oct-19, Volume: 43, Issue:21
Synthesis and antiviral activity of 4-benzyl pyridinone derivatives as potent and selective non-nucleoside human immunodeficiency virus type 1 reverse transcriptase inhibitors.
AID199983Inhibition of HIV-1 reverse transcriptase.2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Molecular modeling calculations of HIV-1 reverse transcriptase nonnucleoside inhibitors: correlation of binding energy with biological activity for novel 2-aryl-substituted benzimidazole analogues.
AID105522Concentration which reduced the cytopathic effect of HIV-1 in MT-4 infected cells1995Journal of medicinal chemistry, Dec-08, Volume: 38, Issue:25
Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs.
AID46059Inhibition of wild type HIV-1-IIIB strain replication in CEM-SS cells1995Journal of medicinal chemistry, Nov-10, Volume: 38, Issue:23
A new series of pyridinone derivatives as potent non-nucleoside human immunodeficiency virus type 1 specific reverse transcriptase inhibitors.
AID1795367HIV-1 RT Assay from Article 10.1021/jm950639r: \\Phenethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse transcriptase inhibitors. 2. Synthesis and further structure-activity relationship studies of PETT analogs.\\1996Journal of medicinal chemistry, Oct-11, Volume: 39, Issue:21
Phenethylthiazolylthiourea (PETT) compounds as a new class of HIV-1 reverse transcriptase inhibitors. 2. Synthesis and further structure-activity relationship studies of PETT analogs.
AID1795381HIV-1 RT Assay from Article 10.1021/jm00061a022: \\5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase.\\1993Journal of medicinal chemistry, Apr-30, Volume: 36, Issue:9
5-chloro-3-(phenylsulfonyl)indole-2-carboxamide: a novel, non-nucleoside inhibitor of HIV-1 reverse transcriptase.
AID1795346HIV-1 RT Assay from Article 10.1021/jm00025a010: \\Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs.\\1995Journal of medicinal chemistry, Dec-08, Volume: 38, Issue:25
Phenethylthiazolethiourea (PETT) compounds, a new class of HIV-1 reverse transcriptase inhibitors. 1. Synthesis and basic structure-activity relationship studies of PETT analogs.
AID977608Experimentally measured binding affinity data (IC50) for protein-ligand complexes derived from PDB1996Journal of molecular biology, Dec-20, Volume: 264, Issue:5
Crystal structures of 8-Cl and 9-Cl TIBO complexed with wild-type HIV-1 RT and 8-Cl TIBO complexed with the Tyr181Cys HIV-1 RT drug-resistant mutant.
AID977610Experimentally measured binding affinity data (Ki) for protein-ligand complexes derived from PDB1995Structure (London, England : 1993), Sep-15, Volume: 3, Issue:9
The structure of HIV-1 reverse transcriptase complexed with 9-chloro-TIBO: lessons for inhibitor design.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (64)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's56 (87.50)18.2507
2000's6 (9.38)29.6817
2010's2 (3.13)24.3611
2020's0 (0.00)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 9.96

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index9.96 (24.57)
Research Supply Index4.20 (2.92)
Research Growth Index4.17 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (9.96)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (1.54%)5.53%
Reviews6 (9.23%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other58 (89.23%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]