Page last updated: 2024-12-06

4-aminoquinoline

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

4-aminoquinoline is a heterocyclic organic compound with the formula C9H8N2. It is a white solid that is soluble in most organic solvents. 4-aminoquinoline is a versatile building block in organic synthesis. For example, it is used to synthesize the antimalarial drug chloroquine, which was originally developed in the 1940s by the German pharmaceutical company Bayer. Chloroquine acts by inhibiting the growth of the malaria parasite in the red blood cells. 4-aminoquinoline has also been investigated as a potential anticancer agent. Several derivatives of 4-aminoquinoline have shown promising results in preclinical studies, and some are currently in clinical trials. 4-aminoquinoline is also an important starting material for the synthesis of various dyes and pigments. For example, the yellow dye known as quinoline yellow is derived from 4-aminoquinoline. The compound is also an important intermediate in the synthesis of certain pharmaceuticals. It is widely studied due to its potential applications in medicine, chemistry, and material science.'

Cross-References

ID SourceID
PubMed CID68476
CHEMBL ID58146
SCHEMBL ID278276
MeSH IDM0042325

Synonyms (46)

Synonym
AC-1256
4-quinolinamine
AE-848/32807060
4-aminoquinoline
quinolin-4-amine
578-68-7
bdbm10450
4-aminoquinoline 7
ccris 1679
AKOS000482611
CHEMBL58146
F2179-0001
A26215
STK694411
4-aminoguinoline
unii-gte5p5l97n
gte5p5l97n ,
quinolin-4-yl-amine
139266-00-5
4-quinolylamine
FT-0645211
PS-3999
AM20061339
1lm ,
AB06141
AB4073
4-aminoquinoline [vandf]
quinoline, 4-amino-
SCHEMBL278276
AB00994061-03
4-amino-quinoline
4-quinolinylamine
4-amino quinoline
AB00994061-01
quinolin-4-ylamine
DTXSID70206491
J-524176
4-aminoquinoline, aldrichcpr
CS-W004931
Q4637104
SY017843
quinolin-4(1h)-imine
mfcd00463448
EN300-37247
NCGC00342714-01
4(1h)-quinolinimine(9ci)

Research Excerpts

Pharmacokinetics

The pharmacodynamic interaction between retinol and 4-aminoquinolines has been investigated in 29 fresh isolates of Plasmodium falciparum. During lead optimization, team identified 4-Aminoquinoline series and several compounds from this series were investigated in rat and dog pharmacokinetic studies.

ExcerptReferenceRelevance
"The pharmacodynamic interaction between retinol and 4-aminoquinolines has been investigated in 29 fresh isolates of Plasmodium falciparum."( Pharmacodynamic interaction between 4-aminoquinolines and retinol in Plasmodium falciparum in vitro.
Congpuong, K; Frank, C; Ley, B; Sirichaisinthop, J; Wernsdorfer, G; Wernsdorfer, WH, 2008
)
0.87
" Extensive in vitro screening and in vivo pharmacokinetic studies in mice helped to identify two lead molecules, 18 and 4, with promising in vitro therapeutic efficacy, improved ADMET properties, low risk for drug-drug interactions, and desirable pharmacokinetic profiles."( Development of a new generation of 4-aminoquinoline antimalarial compounds using predictive pharmacokinetic and toxicology models.
Catz, P; DeRisi, JL; Furniss, MJ; Green, CE; Guy, RK; Iyer, LV; LeValley, SE; Madrid, PB; Mirsalis, JC; Rausch, LL; Ray, S, 2010
)
0.64
" This study characterizes its pharmacokinetic properties."( Pharmacokinetics of ferroquine, a novel 4-aminoquinoline, in asymptomatic carriers of Plasmodium falciparum infections.
Biot, C; Dal-Bianco, MP; Filali-Ansary, A; Issifou, S; Kremsner, PG; Lell, B; Mazuir, F; Mombo-Ngoma, G; Ospina Salazar, CL; Ramharter, M; Supan, C; Ter-Minassian, D, 2012
)
0.65
" During lead optimization, team identified 4-aminoquinoline series and several compounds from this series were investigated in rat and dog pharmacokinetic studies."( Understanding Pharmacokinetic Disconnect in Preclinical Species for 4-Aminoquinolines: Consequences of Low Permeability and High P-glycoprotein Efflux Ratio on Rat and Dog Oral Pharmacokinetics.
Bertin, J; Casillas, LN; DeMartino, MP; Haile, PA; Mahajan, MK; Marquis, RW; Nagilla, R; Reilly, MA; Rivera, EJ; Sun, HH; Votta, BJ, 2020
)
1.06

Compound-Compound Interactions

ExcerptReferenceRelevance
"To overcome the declining efficacy of the 4-aminoquinolines in Papua New Guinea, sulfadoxine/pyrimethamine (SP) was combined with the 4-aminoquinolines as the first line treatment for falciparum malaria since 2000."( Rapid selection of dhfr mutant allele in Plasmodium falciparum isolates after the introduction of sulfadoxine/pyrimethamine in combination with 4-aminoquinolines in Papua New Guinea.
Björkman, A; Hwaihwanje, I; Kaneko, A; Kobayakawa, T; Mita, T; Osawa, H; Takahashi, N; Tanabe, K; Tsukahara, T, 2006
)
0.8
" Thus, we are in dire need of alternate chemotherapeutic agents which in combination with artemisinin (or its analogues) are efficacious against chloroquine-resistant strains."( In vitro synergistic interaction of potent 4-aminoquinolines in combination with dihydroartemisinin against chloroquine-resistant Plasmodium falciparum.
Agarwal, D; Awasthi, SK; Gupta, RD; Singh, S, 2019
)
0.78

Bioavailability

ExcerptReferenceRelevance
" Mean NTBI oral bioavailability was generally higher than the other leads (>/=68%)."( Comparative preclinical drug metabolism and pharmacokinetic evaluation of novel 4-aminoquinoline anti-malarials.
Bambal, R; Davis, CB; Hugger, E; Moorthy, GS; O'Neill, PM; Park, BK; Shone, AE; Ward, SA; Xiang, H, 2009
)
0.58
" Even though oral bioavailability determined for compound 12 was low, novel quinoline C-3'-substituted 15-membered azalides represent an interesting subclass of antimalarial macrolides that need further research and evaluation."( Novel hybrid molecules based on 15-membered azalide as potential antimalarial agents.
Alihodžić, S; Ferrer, S; Herreros, E; Landek, G; Perić, M; Pešić, D; Spaventi, R; Starčević, K; Toplak, A, 2012
)
0.38

Dosage Studied

ExcerptRelevanceReference
" Thus, the clinical dosing required for these compounds would probably be greater for chloroquine-resistant strains than for chloroquine-susceptible strains."( 4-aminoquinoline analogs of chloroquine with shortened side chains retain activity against chloroquine-resistant Plasmodium falciparum.
Dorn, A; Girometta, MA; Guenzi, A; Hofheinz, W; Huber, W; Jaquet, C; Jolidon, S; Masciadri, R; Matile, H; Peters, W; Richter, WF; Ridley, RG; Thaithong, S; Urwyler, H, 1996
)
1.74
" Based on its structure and riboswitch dose-response activity we identified that the antagonist activity of hydroxychloroquine is consistent with it being a conformationally restricted analog of the polyamine spermidine."( 4-Aminoquinolines modulate RNA structure and function: Pharmacophore implications of a conformationally restricted polyamine.
Aldhumani, AH; Boesger, H; Herath, D; Hines, JV; Hossain, MI; Myers, M, 2023
)
2.35
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Protein Targets (2)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
AcetylcholinesteraseRattus norvegicus (Norway rat)IC50 (µMol)152.85000.00020.52597.2000AID1796455
[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)
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (17)

Processvia Protein(s)Taxonomy
superoxide anion generationNeutrophil cytosol factor 1Homo sapiens (human)
protein targeting to membraneNeutrophil cytosol factor 1Homo sapiens (human)
superoxide metabolic processNeutrophil cytosol factor 1Homo sapiens (human)
cellular defense responseNeutrophil cytosol factor 1Homo sapiens (human)
cellular response to reactive oxygen speciesNeutrophil cytosol factor 1Homo sapiens (human)
superoxide anion generationNeutrophil cytosol factor 1Homo sapiens (human)
innate immune responseNeutrophil cytosol factor 1Homo sapiens (human)
respiratory burstNeutrophil cytosol factor 1Homo sapiens (human)
positive regulation of epidermal growth factor-activated receptor activityNeutrophil cytosol factor 1Homo sapiens (human)
positive regulation of DNA-templated transcriptionNeutrophil cytosol factor 1Homo sapiens (human)
positive regulation of JNK cascadeNeutrophil cytosol factor 1Homo sapiens (human)
positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transductionNeutrophil cytosol factor 1Homo sapiens (human)
regulation of respiratory burst involved in inflammatory responseNeutrophil cytosol factor 1Homo sapiens (human)
cellular response to cadmium ionNeutrophil cytosol factor 1Homo sapiens (human)
cellular response to glucose stimulusNeutrophil cytosol factor 1Homo sapiens (human)
cellular response to testosterone stimulusNeutrophil cytosol factor 1Homo sapiens (human)
positive regulation of p38MAPK cascadeNeutrophil cytosol factor 1Homo sapiens (human)
reactive oxygen species biosynthetic processNeutrophil cytosol factor 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (7)

Processvia Protein(s)Taxonomy
protein bindingNeutrophil cytosol factor 1Homo sapiens (human)
electron transfer activityNeutrophil cytosol factor 1Homo sapiens (human)
superoxide-generating NAD(P)H oxidase activityNeutrophil cytosol factor 1Homo sapiens (human)
SH3 domain bindingNeutrophil cytosol factor 1Homo sapiens (human)
phosphatidylinositol bindingNeutrophil cytosol factor 1Homo sapiens (human)
phosphatidylinositol-3,4-bisphosphate bindingNeutrophil cytosol factor 1Homo sapiens (human)
superoxide-generating NADPH oxidase activator activityNeutrophil cytosol factor 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (9)

Processvia Protein(s)Taxonomy
cytosolNeutrophil cytosol factor 1Homo sapiens (human)
plasma membraneNeutrophil cytosol factor 1Homo sapiens (human)
cytoplasmic side of plasma membraneNeutrophil cytosol factor 1Homo sapiens (human)
membraneNeutrophil cytosol factor 1Homo sapiens (human)
dendriteNeutrophil cytosol factor 1Homo sapiens (human)
phagolysosomeNeutrophil cytosol factor 1Homo sapiens (human)
NADPH oxidase complexNeutrophil cytosol factor 1Homo sapiens (human)
neuronal cell bodyNeutrophil cytosol factor 1Homo sapiens (human)
cytoplasmNeutrophil cytosol factor 1Homo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (14)

Assay IDTitleYearJournalArticle
AID32092Inhibition of acetylcholinesterase activity in rat cerebral cortex homogenate, in the presence of a specific butyrylcholinesterase (BChE) inhibitor; ethopropazine1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Heterodimeric tacrine-based acetylcholinesterase inhibitors: investigating ligand-peripheral site interactions.
AID158544In vitro antiplasmodial activity against Plasmodium falciparum D102000Journal of medicinal chemistry, Jan-27, Volume: 43, Issue:2
Structure-function relationships in aminoquinolines: effect of amino and chloro groups on quinoline-hematin complex formation, inhibition of beta-hematin formation, and antiplasmodial activity.
AID1582676Binding affinity to immobilized recombinant human His-tagged p47phox SH3A-B domain (151 to 285 residues) expressed in Escherichia coli BL21 (DE3) cells assessed as dissociation constant by SPR assay2020Journal of medicinal chemistry, 02-13, Volume: 63, Issue:3
Developing Inhibitors of the p47phox-p22phox Protein-Protein Interaction by Fragment-Based Drug Discovery.
AID29176Dissociation constent of compound at 20 degree C1989Journal of medicinal chemistry, Aug, Volume: 32, Issue:8
2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 11. Quinolylmethyl analogues with basic substituents conveying specificity.
AID554321Inhibition of Leishmania major PTR1 at 500 uM2011Journal of medicinal chemistry, Jan-13, Volume: 54, Issue:1
Virtual screening identification of nonfolate compounds, including a CNS drug, as antiparasitic agents inhibiting pteridine reductase.
AID393144Antitubercular activity against Mycobacterium tuberculosis H37Rv after 5 days by microplate alamar blue assay2009Bioorganic & medicinal chemistry, Feb-15, Volume: 17, Issue:4
Synthesis and in vitro antitubercular activity of a series of quinoline derivatives.
AID1764407Agonist activity at Gal4-fused human Nurr1 LBD expressed in HEK293T cells co-expressing firefly luciferase assessed as luciferase activity at 300 uM incubated for 12 to 14 hrs by hybrid reporter gene assay2021Journal of medicinal chemistry, 03-11, Volume: 64, Issue:5
Fragment-like Chloroquinolineamines Activate the Orphan Nuclear Receptor Nurr1 and Elucidate Activation Mechanisms.
AID753876Inhibition of beta-hematin formation after 60 mins by colorimetric assay relative to Fe(3)PP92013Bioorganic & medicinal chemistry, Jul-01, Volume: 21, Issue:13
Structure-activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods.
AID32128Inhibitory activity against rat brain Acetylcholinesterase using rat cortex homogenate relative to Tacrine.1999Journal of medicinal chemistry, Oct-07, Volume: 42, Issue:20
Heterodimeric tacrine-based acetylcholinesterase inhibitors: investigating ligand-peripheral site interactions.
AID226297Inhibition of Beta-hematin (hemozoin) formation; No inhibition.2000Journal of medicinal chemistry, Jan-27, Volume: 43, Issue:2
Structure-function relationships in aminoquinolines: effect of amino and chloro groups on quinoline-hematin complex formation, inhibition of beta-hematin formation, and antiplasmodial activity.
AID219087Association constant with ferriprotoporphyrin IX.2000Journal of medicinal chemistry, Jan-27, Volume: 43, Issue:2
Structure-function relationships in aminoquinolines: effect of amino and chloro groups on quinoline-hematin complex formation, inhibition of beta-hematin formation, and antiplasmodial activity.
AID1582668Covalent inhibition of recombinant human His-tagged p47phox SH3A-B domain (151 to 285 residues) expressed in Escherichia coli BL21 (DE3) cells interaction with Cy5-p22phox149-162 incubated for 10 mins by fluorescence polarization competition assay2020Journal of medicinal chemistry, 02-13, Volume: 63, Issue:3
Developing Inhibitors of the p47phox-p22phox Protein-Protein Interaction by Fragment-Based Drug Discovery.
AID753877Binding affinity to ferriprotoporphyrin 9 at pH 7.5 by UV-vis spectrophotometric analysis in presence of 40% DMSO2013Bioorganic & medicinal chemistry, Jul-01, Volume: 21, Issue:13
Structure-activity relationships for ferriprotoporphyrin IX association and β-hematin inhibition by 4-aminoquinolines using experimental and ab initio methods.
AID1796455Enzyme Inhibition Assay from Article 10.1016/s0968-0896(99)00178-9: \\Dual-site binding of bivalent 4-aminopyridine- and 4-aminoquinoline-based AChE inhibitors: contribution of the hydrophobic alkylene tether to monomer and dimer affinities.\\1999Bioorganic & medicinal chemistry, Nov, Volume: 7, Issue:11
Dual-site binding of bivalent 4-aminopyridine- and 4-aminoquinoline-based AChE inhibitors: contribution of the hydrophobic alkylene tether to monomer and dimer affinities.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (226)

TimeframeStudies, This Drug (%)All Drugs %
pre-199046 (20.35)18.7374
1990's18 (7.96)18.2507
2000's36 (15.93)29.6817
2010's97 (42.92)24.3611
2020's29 (12.83)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 41.74

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 strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index41.74 (24.57)
Research Supply Index5.47 (2.92)
Research Growth Index4.90 (4.65)
Search Engine Demand Index61.15 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (41.74)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews19 (8.02%)6.00%
Case Studies3 (1.27%)4.05%
Observational0 (0.00%)0.25%
Other215 (90.72%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]