Page last updated: 2024-11-11

a 286982

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Description

A 286982: inhibits the interaction between leukocyte function-associated antigen-1 and intracellular adhesion molecule-1; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9846729
CHEMBL ID19677
SCHEMBL ID5829786
SCHEMBL ID12063498
MeSH IDM0372587

Synonyms (34)

Synonym
1-(4-acetylpiperazin-1-yl)-3-(4-(2-isopropylphenylthio)-3-nitrophenyl)prop-2-en-1-one
1-(4-acetyl-piperazin-1-yl)-3-[4-(2-isopropyl-phenylsulfanyl)-3-nitro-phenyl]-propenone
bdbm50092956
CHEMBL19677 ,
a-286982
gtpl6592
(e)-1-(4-acetylpiperazin-1-yl)-3-[3-nitro-4-(2-propan-2-ylphenyl)sulfanylphenyl]prop-2-en-1-one
a286982
2-propen-1-one, 1-(4-acetyl-1-piperazinyl)-3-(4-((2-(1-methylethyl)phenyl)thio)-3-nitrophenyl)-
2-isopropylphenyl 2-nitro-4-(((4-acetylpiperazin-1-yl)carbonyl)ethenyl)phenyl sulfide
piperazine, 1-acetyl-4-((2e)-3-(4-((2-(1-methylethyl)phenyl)thio)-3-nitrophenyl)-1-oxo-2-propenyl)-
a-286,982
a 286982
2-propen-1-one, 1-(4-acetyl-1-piperazinyl)-3-(4-((2-(1-methylethyl)phenyl)thio)-3-nitrophenyl)-, (2e)-
unii-5i8wfs075a
280749-17-9
5i8wfs075a ,
a 286,982
SCHEMBL5829786
SCHEMBL12063498
(2e)-1-(4-acetyl-1-piperazinyl)-3-[4-[[2-(1-methylethyl)phenyl]thio]-3-nitrophenyl]-2-propen-1-one
AKOS024458044
J-016962
Q27074059
AS-16426
A899560
HY-107587
EX-A4719
CS-0028915
(e)-1-(4-acetylpiperazin-1-yl)-3-(4-((2-isopropylphenyl)thio)-3-nitrophenyl)prop-2-en-1-one
DTXSID601328277
AC-36582
F77491
Z2607847156

Research Excerpts

Bioavailability

ExcerptReferenceRelevance
" In addition to excellent in vitro potency, 6q shows good pharmacokinetic properties and its ethyl ester (6t) demonstrates good oral bioavailability in both mouse and rat."( Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists.
Arbitrario, JP; Arkin, MR; Barr, KJ; Bui, M; Chen, T; Cunningham, BC; Evanchik, MJ; Flanagan, WM; Hanan, EJ; Hoch, U; Huen, K; Hyde, J; Kumer, JL; Lac, T; Lawrence, CE; Martell, JR; Oslob, JD; Paulvannan, K; Prabhu, S; Shen, W; Silverman, JA; Wright, J; Yu, CH; Zhong, M; Zhu, J, 2010
)
0.36
"Many lead compounds fail to reach clinical trials despite being potent because of low bioavailability attributed to their insufficient solubility making solubility a primary and crucial factor in early phase drug discovery."( Structural modification aimed for improving solubility of lead compounds in early phase drug discovery.
Baidya, ATK; Das, B; Kumar, R; Mathew, AT; Yadav, AK, 2022
)
0.72
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (3)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Integrin beta-2Homo sapiens (human)IC50 (µMol)0.04120.00080.59053.7800AID100087; AID181507; AID501388; AID94613; AID99583
Intercellular adhesion molecule 1Homo sapiens (human)IC50 (µMol)0.04020.00301.212210.0000AID100087; AID181507; AID501388; AID94613; AID94747; AID99583
Integrin alpha-LHomo sapiens (human)IC50 (µMol)0.04170.00080.60203.7800AID100087; AID181507; AID501388; AID91750; AID94613; AID99583
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (51)

Processvia Protein(s)Taxonomy
microglial cell activationIntegrin beta-2Homo sapiens (human)
receptor-mediated endocytosisIntegrin beta-2Homo sapiens (human)
phagocytosis, engulfmentIntegrin beta-2Homo sapiens (human)
apoptotic processIntegrin beta-2Homo sapiens (human)
inflammatory responseIntegrin beta-2Homo sapiens (human)
cell adhesionIntegrin beta-2Homo sapiens (human)
leukocyte cell-cell adhesionIntegrin beta-2Homo sapiens (human)
cell-matrix adhesionIntegrin beta-2Homo sapiens (human)
integrin-mediated signaling pathwayIntegrin beta-2Homo sapiens (human)
cell-cell signalingIntegrin beta-2Homo sapiens (human)
regulation of cell shapeIntegrin beta-2Homo sapiens (human)
neutrophil chemotaxisIntegrin beta-2Homo sapiens (human)
receptor internalizationIntegrin beta-2Homo sapiens (human)
positive regulation of superoxide anion generationIntegrin beta-2Homo sapiens (human)
heterotypic cell-cell adhesionIntegrin beta-2Homo sapiens (human)
endodermal cell differentiationIntegrin beta-2Homo sapiens (human)
receptor clusteringIntegrin beta-2Homo sapiens (human)
positive regulation of neutrophil degranulationIntegrin beta-2Homo sapiens (human)
negative regulation of dopamine metabolic processIntegrin beta-2Homo sapiens (human)
regulation of peptidyl-tyrosine phosphorylationIntegrin beta-2Homo sapiens (human)
cellular response to low-density lipoprotein particle stimulusIntegrin beta-2Homo sapiens (human)
positive regulation of protein targeting to membraneIntegrin beta-2Homo sapiens (human)
amyloid-beta clearanceIntegrin beta-2Homo sapiens (human)
cell-cell adhesionIntegrin beta-2Homo sapiens (human)
cell-cell adhesion via plasma-membrane adhesion moleculesIntegrin beta-2Homo sapiens (human)
positive regulation of leukocyte adhesion to vascular endothelial cellIntegrin beta-2Homo sapiens (human)
neutrophil migrationIntegrin beta-2Homo sapiens (human)
positive regulation of prostaglandin-E synthase activityIntegrin beta-2Homo sapiens (human)
cell adhesion mediated by integrinIntegrin beta-2Homo sapiens (human)
regulation of leukocyte mediated cytotoxicityIntercellular adhesion molecule 1Homo sapiens (human)
T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cellIntercellular adhesion molecule 1Homo sapiens (human)
T cell antigen processing and presentationIntercellular adhesion molecule 1Homo sapiens (human)
positive regulation of cellular extravasationIntercellular adhesion molecule 1Homo sapiens (human)
cell adhesionIntercellular adhesion molecule 1Homo sapiens (human)
heterophilic cell-cell adhesion via plasma membrane cell adhesion moleculesIntercellular adhesion molecule 1Homo sapiens (human)
leukocyte cell-cell adhesionIntercellular adhesion molecule 1Homo sapiens (human)
membrane to membrane dockingIntercellular adhesion molecule 1Homo sapiens (human)
cell adhesion mediated by integrinIntercellular adhesion molecule 1Homo sapiens (human)
adhesion of symbiont to hostIntercellular adhesion molecule 1Homo sapiens (human)
symbiont entry into host cellIntercellular adhesion molecule 1Homo sapiens (human)
receptor-mediated virion attachment to host cellIntercellular adhesion molecule 1Homo sapiens (human)
leukocyte migrationIntercellular adhesion molecule 1Homo sapiens (human)
establishment of endothelial barrierIntercellular adhesion molecule 1Homo sapiens (human)
positive regulation of ERK1 and ERK2 cascadeIntercellular adhesion molecule 1Homo sapiens (human)
cellular response to glucose stimulusIntercellular adhesion molecule 1Homo sapiens (human)
T cell extravasationIntercellular adhesion molecule 1Homo sapiens (human)
regulation of ruffle assemblyIntercellular adhesion molecule 1Homo sapiens (human)
negative regulation of extrinsic apoptotic signaling pathway via death domain receptorsIntercellular adhesion molecule 1Homo sapiens (human)
cellular response to amyloid-betaIntercellular adhesion molecule 1Homo sapiens (human)
cellular response to leukemia inhibitory factorIntercellular adhesion molecule 1Homo sapiens (human)
negative regulation of endothelial cell apoptotic processIntercellular adhesion molecule 1Homo sapiens (human)
T cell activation via T cell receptor contact with antigen bound to MHC molecule on antigen presenting cellIntegrin alpha-LHomo sapiens (human)
phagocytosisIntegrin alpha-LHomo sapiens (human)
inflammatory responseIntegrin alpha-LHomo sapiens (human)
cell adhesionIntegrin alpha-LHomo sapiens (human)
heterophilic cell-cell adhesion via plasma membrane cell adhesion moleculesIntegrin alpha-LHomo sapiens (human)
leukocyte cell-cell adhesionIntegrin alpha-LHomo sapiens (human)
cell-matrix adhesionIntegrin alpha-LHomo sapiens (human)
signal transductionIntegrin alpha-LHomo sapiens (human)
integrin-mediated signaling pathwayIntegrin alpha-LHomo sapiens (human)
memory T cell extravasationIntegrin alpha-LHomo sapiens (human)
receptor clusteringIntegrin alpha-LHomo sapiens (human)
cell-cell adhesionIntegrin alpha-LHomo sapiens (human)
cell adhesion mediated by integrinIntegrin alpha-LHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (13)

Processvia Protein(s)Taxonomy
cargo receptor activityIntegrin beta-2Homo sapiens (human)
amyloid-beta bindingIntegrin beta-2Homo sapiens (human)
complement component C3b bindingIntegrin beta-2Homo sapiens (human)
integrin bindingIntegrin beta-2Homo sapiens (human)
protein bindingIntegrin beta-2Homo sapiens (human)
protein kinase bindingIntegrin beta-2Homo sapiens (human)
ICAM-3 receptor activityIntegrin beta-2Homo sapiens (human)
heat shock protein bindingIntegrin beta-2Homo sapiens (human)
metal ion bindingIntegrin beta-2Homo sapiens (human)
cell adhesion molecule bindingIntegrin beta-2Homo sapiens (human)
virus receptor activityIntercellular adhesion molecule 1Homo sapiens (human)
transmembrane signaling receptor activityIntercellular adhesion molecule 1Homo sapiens (human)
integrin bindingIntercellular adhesion molecule 1Homo sapiens (human)
protein bindingIntercellular adhesion molecule 1Homo sapiens (human)
signaling receptor activityIntercellular adhesion molecule 1Homo sapiens (human)
protein bindingIntegrin alpha-LHomo sapiens (human)
ICAM-3 receptor activityIntegrin alpha-LHomo sapiens (human)
metal ion bindingIntegrin alpha-LHomo sapiens (human)
cell adhesion molecule bindingIntegrin alpha-LHomo sapiens (human)
integrin bindingIntegrin alpha-LHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (20)

Processvia Protein(s)Taxonomy
plasma membraneIntegrin beta-2Homo sapiens (human)
external side of plasma membraneIntegrin beta-2Homo sapiens (human)
cell surfaceIntegrin beta-2Homo sapiens (human)
membraneIntegrin beta-2Homo sapiens (human)
integrin alphaL-beta2 complexIntegrin beta-2Homo sapiens (human)
integrin alphaM-beta2 complexIntegrin beta-2Homo sapiens (human)
integrin alphaX-beta2 complexIntegrin beta-2Homo sapiens (human)
specific granule membraneIntegrin beta-2Homo sapiens (human)
plasma membrane raftIntegrin beta-2Homo sapiens (human)
extracellular exosomeIntegrin beta-2Homo sapiens (human)
tertiary granule membraneIntegrin beta-2Homo sapiens (human)
ficolin-1-rich granule membraneIntegrin beta-2Homo sapiens (human)
extracellular vesicleIntegrin beta-2Homo sapiens (human)
integrin complexIntegrin beta-2Homo sapiens (human)
receptor complexIntegrin beta-2Homo sapiens (human)
focal adhesionIntegrin beta-2Homo sapiens (human)
cell surfaceIntegrin beta-2Homo sapiens (human)
immunological synapseIntercellular adhesion molecule 1Homo sapiens (human)
extracellular spaceIntercellular adhesion molecule 1Homo sapiens (human)
plasma membraneIntercellular adhesion molecule 1Homo sapiens (human)
focal adhesionIntercellular adhesion molecule 1Homo sapiens (human)
external side of plasma membraneIntercellular adhesion molecule 1Homo sapiens (human)
cell surfaceIntercellular adhesion molecule 1Homo sapiens (human)
membraneIntercellular adhesion molecule 1Homo sapiens (human)
membrane raftIntercellular adhesion molecule 1Homo sapiens (human)
collagen-containing extracellular matrixIntercellular adhesion molecule 1Homo sapiens (human)
extracellular exosomeIntercellular adhesion molecule 1Homo sapiens (human)
plasma membraneIntercellular adhesion molecule 1Homo sapiens (human)
plasma membraneIntegrin alpha-LHomo sapiens (human)
cell surfaceIntegrin alpha-LHomo sapiens (human)
membraneIntegrin alpha-LHomo sapiens (human)
integrin alphaL-beta2 complexIntegrin alpha-LHomo sapiens (human)
specific granule membraneIntegrin alpha-LHomo sapiens (human)
extracellular exosomeIntegrin alpha-LHomo sapiens (human)
integrin complexIntegrin alpha-LHomo sapiens (human)
external side of plasma membraneIntegrin alpha-LHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (23)

Assay IDTitleYearJournalArticle
AID1866081Inhibition of Integrin alpha-L (unknown origin)/Intercellular adhesion molecule 1 (unknown origin) interaction2022Bioorganic & medicinal chemistry, 02-15, Volume: 56Structural modification aimed for improving solubility of lead compounds in early phase drug discovery.
AID99583Inhibition of JY-8 cell adhesion via leukocyte function associated antigen 1 (LFA-1) to ICAM-12001Journal of medicinal chemistry, Apr-12, Volume: 44, Issue:8
Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties.
AID181507Ability to antagonise the Leukocyte function-associated Antigen-1/ Intracellular Adhesion molecule-1 interaction (LFA-1/ICAM-1)2001Journal of medicinal chemistry, Aug-30, Volume: 44, Issue:18
Discovery of potent antagonists of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. 3. Amide (C-ring) structure-activity relationship and improvement of overall properties of arylthio cinnamides.
AID25883Half life was determined after intravenous administration2001Journal of medicinal chemistry, Apr-12, Volume: 44, Issue:8
Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties.
AID1866020Thermodynamic aqueous solubility of the compound2022Bioorganic & medicinal chemistry, 02-15, Volume: 56Structural modification aimed for improving solubility of lead compounds in early phase drug discovery.
AID13521AUC(area under curve) was determined after oral administration in rats2001Journal of medicinal chemistry, Apr-12, Volume: 44, Issue:8
Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties.
AID100087Ability to block the interaction between integrin LFA-1 and its adhesion partner ICAM-1 in a time-resolved fluorescent LFA-1/ICAM-1 biochemical interaction assay2000Journal of medicinal chemistry, Oct-19, Volume: 43, Issue:21
Discovery of novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 1. Identification of an additional binding pocket based on an anilino diaryl sulfide lead.
AID27215Half life period after iv dose2001Journal of medicinal chemistry, Aug-30, Volume: 44, Issue:18
Discovery of potent antagonists of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. 3. Amide (C-ring) structure-activity relationship and improvement of overall properties of arylthio cinnamides.
AID501388Inhibition of LFA1/ICAM1 interaction in human Hut-78 cells by cell migration assay2010Bioorganic & medicinal chemistry letters, Sep-01, Volume: 20, Issue:17
Discovery of tetrahydroisoquinoline (THIQ) derivatives as potent and orally bioavailable LFA-1/ICAM-1 antagonists.
AID94747Evaluated for its ability to block the adherence of JY-8 cells to immobilized ICAM-1.2000Journal of medicinal chemistry, Oct-19, Volume: 43, Issue:21
Discovery of novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 1. Identification of an additional binding pocket based on an anilino diaryl sulfide lead.
AID14663Pharmacokinetic parameter was evaluated in rats2001Journal of medicinal chemistry, Apr-12, Volume: 44, Issue:8
Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties.
AID91750Inhibition of intercellular adhesion molecule-1 (ICAM-1) binding to recombinant LFA-1, range(30-60)2001Journal of medicinal chemistry, Dec-06, Volume: 44, Issue:25
Discovery of novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. 4. Structure-activity relationship of substituents on the benzene ring of the cinnamide.
AID94613Inhibition of LFA-1 mediated JY-8 cell adhesion to ICAM-1, range(12-60)2001Journal of medicinal chemistry, Dec-06, Volume: 44, Issue:25
Discovery of novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. 4. Structure-activity relationship of substituents on the benzene ring of the cinnamide.
AID18002Bioavailability was evaluated in rats2001Journal of medicinal chemistry, Apr-12, Volume: 44, Issue:8
Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties.
AID23901Plasma clearance after iv dose in rat2001Journal of medicinal chemistry, Aug-30, Volume: 44, Issue:18
Discovery of potent antagonists of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. 3. Amide (C-ring) structure-activity relationship and improvement of overall properties of arylthio cinnamides.
AID25884Half life was determined after oral administration in rats; Not determined2001Journal of medicinal chemistry, Apr-12, Volume: 44, Issue:8
Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties.
AID29923Solubility after iv dose2001Journal of medicinal chemistry, Aug-30, Volume: 44, Issue:18
Discovery of potent antagonists of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. 3. Amide (C-ring) structure-activity relationship and improvement of overall properties of arylthio cinnamides.
AID22401Pharmacokinetic parameter was evaluated in rats which is represented as Vbeta2001Journal of medicinal chemistry, Apr-12, Volume: 44, Issue:8
Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties.
AID1564237Inhibition of recombinant LFA1/ICAM1 (unknown origin) interaction incubated for 1 hr by time resolved fluorimetry2019European journal of medicinal chemistry, Nov-01, Volume: 181Cinnamamide: An insight into the pharmacological advances and structure-activity relationships.
AID22006solubility in rats2001Journal of medicinal chemistry, Apr-12, Volume: 44, Issue:8
Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties.
AID13520AUC(area under curve) was determined after intravenous administration in rats2001Journal of medicinal chemistry, Apr-12, Volume: 44, Issue:8
Novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 2. Mechanism of inhibition and structure-based improvement of pharmaceutical properties.
AID28078Cmax value after po dose2001Journal of medicinal chemistry, Aug-30, Volume: 44, Issue:18
Discovery of potent antagonists of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. 3. Amide (C-ring) structure-activity relationship and improvement of overall properties of arylthio cinnamides.
AID29816Percent oral bioavailability after po dose2001Journal of medicinal chemistry, Aug-30, Volume: 44, Issue:18
Discovery of potent antagonists of leukocyte function-associated antigen-1/intercellular adhesion molecule-1 interaction. 3. Amide (C-ring) structure-activity relationship and improvement of overall properties of arylthio cinnamides.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (7)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's4 (57.14)29.6817
2010's2 (28.57)24.3611
2020's1 (14.29)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 12.93

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 Index12.93 (24.57)
Research Supply Index2.08 (2.92)
Research Growth Index5.01 (4.65)
Search Engine Demand Index0.00 (26.88)
Search Engine Supply Index0.00 (0.95)

This Compound (12.93)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews2 (28.57%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other5 (71.43%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]