Compounds > gw844520
Page last updated: 2024-11-11

gw844520

Description

GW844520: anti-malarial mitochondrial electron transport inhibitor; structure in first source [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

Cross-References

ID SourceID
PubMed CID9887751
CHEMBL ID467584
SCHEMBL ID4472453
MeSH IDM0507190

Synonyms (14)

Synonym
3-chloro-2,6-dimethyl-5-[4-[4-(trifluoromethoxy)phenoxy]phenyl]-1h-pyridin-4-one
CHEMBL467584
gw844520
gw-844520
137735-25-2
gw 844520
4x9 ,
3-chloro-2,6-dimethyl-5-{4-[4-(trifluoromethoxy)phenoxy]phenyl}pyridin-4-ol
3-chloro-5-(4-(4-trifluoromethoxyphenoxy)phenyl)-2,6-dimethylpyridin-4(1h)-one
3-chloro-5-(4-(4-trifluoromethoxyphenoxy)phenyl)-2,6-dimethyl pyridin-4(1h)-one
SCHEMBL4472453
DTXSID20160296
Q27455192
AKOS040748510

Research Excerpts

Overview

GW844520 is a potent and selective inhibitor of the cytochrome bc1 complex of mitochondrial electron transport.

ExcerptReferenceRelevance
"GW844520 is a potent and selective inhibitor of the cytochrome bc1 complex of mitochondrial electron transport in P. "( Preclinical drug metabolism and pharmacokinetic evaluation of GW844520, a novel anti-malarial mitochondrial electron transport inhibitor.
Bambal, R; Davis, CB; Ferrer, S; Gargallo, D; Han, C; Hugger, E; McSurdy-Freed, J; Moorthy, GS; Xiang, H, 2006)		2.02

Pharmacokinetics

ExcerptReferenceRelevance
" To evaluate full potential of this development candidate, we conducted drug metabolism and pharmacokinetic studies of this novel anti-malarial."( Preclinical drug metabolism and pharmacokinetic evaluation of GW844520, a novel anti-malarial mitochondrial electron transport inhibitor.
Bambal, R; Davis, CB; Ferrer, S; Gargallo, D; Han, C; Hugger, E; McSurdy-Freed, J; Moorthy, GS; Xiang, H, 2006)		0.57

Bioavailability

ExcerptReferenceRelevance
" Oral bioavailability was high (51-100%)."( Preclinical drug metabolism and pharmacokinetic evaluation of GW844520, a novel anti-malarial mitochondrial electron transport inhibitor.
Bambal, R; Davis, CB; Ferrer, S; Gargallo, D; Han, C; Hugger, E; McSurdy-Freed, J; Moorthy, GS; Xiang, H, 2006)		0.57
" In general, the most potent 4-pyridones are lipophilic molecules with poor solubility in aqueous media and low oral bioavailability in pre-clinical species from the solid dosage form."( Potent antimalarial 4-pyridones with improved physico-chemical properties.
Bueno, JM; Chicharro, J; Ferrer, S; Fiandor, JM; Fraile, MT; García, A; García, MC; Gargallo-Viola, D; Gómez, RM; Herreros, E; Lavandera, JL; Lorenzo, M; Manzano, P; Puente, M; Vidal, J, 2011)		0.37
" Selected as a preclinical candidate, ELQ-300 has good oral bioavailability at efficacious doses in mice, is metabolically stable, and is highly active in blocking transmission in rodent models of malaria."( Quinolone-3-diarylethers: a new class of antimalarial drug.
Angulo-Barturen, I; Avery, VM; Bathurst, I; Burrows, JN; Charman, SA; Cross, RM; Delves, MJ; Duffy, S; Ferrer, S; Forquer, IP; Gamo, FJ; Guy, RK; Herreros, E; Jiménez-Díaz, MB; Kelly, JX; Kocken, CHM; Kyle, DE; LaCrue, AN; Li, Y; Manetsch, R; Marfurt, J; Mather, MW; Morrisey, JM; Mutka, T; Nilsen, A; Noviyanti, R; Price, RN; Riscoe, MK; Ryan, E; Saenz, FE; Sanz, LM; Sebayang, BF; Shackleford, DM; Siegl, P; Sinden, RE; Steuten, J; Vaidya, AB; White, KL; Winter, RW; Wirjanata, G; Zeeman, AM, 2013)		0.39

Dosage Studied

ExcerptRelevanceReference
" In general, the most potent 4-pyridones are lipophilic molecules with poor solubility in aqueous media and low oral bioavailability in pre-clinical species from the solid dosage form."( Potent antimalarial 4-pyridones with improved physico-chemical properties.
Bueno, JM; Chicharro, J; Ferrer, S; Fiandor, JM; Fraile, MT; García, A; García, MC; Gargallo-Viola, D; Gómez, RM; Herreros, E; Lavandera, JL; Lorenzo, M; Manzano, P; Puente, M; Vidal, J, 2011)		0.37
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (34)

Assay IDTitleYearJournalArticle
AID617168Chromatographic hydrophobicity index of the compound at pH 7.4 by rapid gradient HPLC analysis2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617179Volume of distribution in CD1 mouse at 0.2 mg/kg, iv2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617186Half life in Beagle dog at 0.05 mg/kg, iv2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID384959Antimalarial activity as reduced parasitaemia against Plasmodium yoelii YM in CD1 mice (Mus musculus) given a single peroral dose2008Journal of medicinal chemistry, May-08, Volume: 51, Issue:9
Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.
AID384958Antimalarial activity as reduced parasitaemia against Plasmodium yoelii YM in CD1 mice (Mus musculus) after 7 peroral doses over 4 days2008Journal of medicinal chemistry, May-08, Volume: 51, Issue:9
Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.
AID384960Antimalarial activity against Plasmodium falciparum 3D7A infected erythrocytes by [3H]hypoxanthine uptake2008Journal of medicinal chemistry, May-08, Volume: 51, Issue:9
Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.
AID1733042Antimalarial activity against ring stage artemisinin-sensitive Plasmodium falciparum F32-TEM assessed as time taken for recrudescence by measuring parasitemia at 7 uM after 48 hrs2021Bioorganic & medicinal chemistry letters, 05-01, Volume: 39Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
AID617184Volume of distribution in Beagle dog at 0.05 mg/kg, iv2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617176Solubility of the compound in PBS at pH 7.42011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID384957Antimalarial activity against Plasmodium falciparum T9-96 infected Rhesus positive human erythrocytes by [3H]hypoxanthine uptake2008Journal of medicinal chemistry, May-08, Volume: 51, Issue:9
Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.
AID617181Half life in CD1 mouse at 0.2 mg/kg, iv2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617173Solubility of the compound in simulated gastric fluid at pH 1.22011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID1733048Antimalarial activity against Plasmodium falciparum assessed as difference of time taken for recrudescence Plasmodium falciparum F32 ART1 between ring stage artemisinin-sensitive Plasmodium falciparum F32-TEM measured at 7 uM after 48 hrs2021Bioorganic & medicinal chemistry letters, 05-01, Volume: 39Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
AID617183Oral bioavailability in Beagle dog at 2 mg/kg2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID420345Antimalarial activity after 48 hrs against Plasmodium falciparum T9-96 by [3H]hypoxanthine uptake2009Bioorganic & medicinal chemistry letters, Jul-01, Volume: 19, Issue:13
Design, synthesis and structure-activity relationships of (1H-pyridin-4-ylidene)amines as potential antimalarials.
AID617180Clearance in CD1 mouse at 0.2 mg/kg, iv2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617166Antimalarial activity against Plasmodium falciparum infected in A-positive human erythrocytes assessed as [3H]-hypoxanthine uptake after 24 hrs by liquid scintillation counter2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617172Intrinsic solubility of the neutral form of compound2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617167Chromatographic hydrophobicity index of the compound at pH 2 by rapid gradient HPLC analysis2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID1733036Selective index, ratio of CC50 for African green monkey Vero cells to IC50 for plasmodium falciparum2021Bioorganic & medicinal chemistry letters, 05-01, Volume: 39Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
AID384962Antimalarial activity as parasite elimination against Plasmodium falciparum infected Aotus monkeys at 10 mg/kg/day for 7 days2008Journal of medicinal chemistry, May-08, Volume: 51, Issue:9
Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.
AID617174Solubility of the compound in fed state simulated intestinal fluid at pH 5.02011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617175Solubility of the compound in fasted state simulated intestinal fluid at pH 6.82011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617171Dissociation constant, pKa of the compound2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617185Clearance in Beagle dog at 0.05 mg/kg, iv2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617170Partition coefficient, log P of the compound2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID1733034Antimalarial activity against artemisinin-sensitive Plasmodium falciparum F32-TEM by SYBR green dye based fluorescence assay2021Bioorganic & medicinal chemistry letters, 05-01, Volume: 39Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
AID617178Oral bioavailability in CD1 mouse at 10 mg/kg2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID1733038Antimalarial activity against ring stage artemisinin-resistant Plasmodium falciparum F32-ART5 assessed as time taken for recrudescence by measuring parasitemia at 7 uM after 48 hrs2021Bioorganic & medicinal chemistry letters, 05-01, Volume: 39Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
AID384961Antimalarial activity against Plasmodium falciparum FCR3-A infected erythrocytes as [3H]hypoxanthine incorporation2008Journal of medicinal chemistry, May-08, Volume: 51, Issue:9
Synthesis and structure-activity relationships of 4-pyridones as potential antimalarials.
AID617182Cmax in Beagle dog at 2 mg/kg, po2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID617169Chromatographic hydrophobicity index of the compound at pH 10.5 by rapid gradient HPLC analysis2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
AID1733035Cytotoxicity against African green monkey Vero cells assessed as inhibition of cell proliferation2021Bioorganic & medicinal chemistry letters, 05-01, Volume: 39Novel molecule combinations and corresponding hybrids targeting artemisinin-resistant Plasmodium falciparum parasites.
AID617177Cmax in CD1 mouse at 10 mg/kg, po2011Bioorganic & medicinal chemistry letters, Sep-15, Volume: 21, Issue:18
Potent antimalarial 4-pyridones with improved physico-chemical properties.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (6)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's0 (0.00)18.2507
2000's3 (50.00)29.6817
2010's2 (33.33)24.3611
2020's1 (16.67)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Reviews0 (0.00%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other6 (100.00%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]
SubstanceRelationship StrengthStudiesTrialsClassesRoles
chloroquine
Chloroquine: The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses.. chloroquine : An aminoquinoline that is quinoline which is substituted at position 4 by a [5-(diethylamino)pentan-2-yl]amino group at at position 7 by chlorine. It is used for the treatment of malaria, hepatic amoebiasis, lupus erythematosus, light-sensitive skin eruptions, and rheumatoid arthritis.		2.7730aminoquinoline;
organochlorine compound;
secondary amino compound;
tertiary amino compound		anticoronaviral agent;
antimalarial;
antirheumatic drug;
autophagy inhibitor;
dermatologic drug
triclosan
[no description available]		2.3110aromatic ether;
dichlorobenzene;
monochlorobenzenes;
phenols		antibacterial agent;
antimalarial;
drug allergen;
EC 1.3.1.9 [enoyl-[acyl-carrier-protein] reductase (NADH)] inhibitor;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor;
fungicide;
persistent organic pollutant;
xenobiotic
carbostyril
Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.. quinolin-2(1H)-one : A quinolone that is 1,2-dihydroquinoline substituted by an oxo group at position 2.		2.0810monohydroxyquinoline;
quinolone		bacterial xenobiotic metabolite
clopidol
pharmcoccide: Russian drug; no other info available 1/1/79		2.4520chloropyridine
mefloquine
(-)-(11S,2'R)-erythro-mefloquine : An optically active form of [2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanol having (-)-(11S,2'R)-erythro-configuration. An antimalarial agent, used in racemic form, which acts as a blood schizonticide; its mechanism of action is unknown.		2.3110[2,8-bis(trifluoromethyl)quinolin-4-yl]-(2-piperidyl)methanolantimalarial
chloroquine diphosphate
[no description available]		2.0410
artemisinin
(+)-artemisinin : A sesquiterpene lactone obtained from sweet wormwood, Artemisia annua, which is used as an antimalarial for the treatment of multi-drug resistant strains of falciparum malaria.		2.3110organic peroxide;
sesquiterpene lactone		antimalarial;
plant metabolite
atovaquone
Atovaquone: A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols.. atovaquone : A naphthoquinone compound having a 4-(4-chlorophenyl)cyclohexyl group at the 2-position and a hydroxy substituent at the 3-position.		340hydroxy-1,2-naphthoquinone
proguanil
Proguanil: A biguanide compound which metabolizes in the body to form cycloguanil, an anti-malaria agent.. proguanil : A biguanide compound which has isopropyl and p-chlorophenyl substituents on the terminal N atoms. A prophylactic antimalarial drug, it works by inhibiting the enzyme dihydrofolate reductase, which is involved in the reproduction of the malaria parasites Plasmodium falciparum and P. vivax within the red blood cells.		2.0810biguanides;
monochlorobenzenes		antimalarial;
antiprotozoal drug;
EC 1.5.1.3 (dihydrofolate reductase) inhibitor
ConditionIndicatedRelationship StrengthStudiesTrials
Infections, Plasmodium
[description not available]		02.4620
Malaria
A protozoan disease caused in humans by four species of the PLASMODIUM genus: PLASMODIUM FALCIPARUM; PLASMODIUM VIVAX; PLASMODIUM OVALE; and PLASMODIUM MALARIAE; and transmitted by the bite of an infected female mosquito of the genus ANOPHELES. Malaria is endemic in parts of Asia, Africa, Central and South America, Oceania, and certain Caribbean islands. It is characterized by extreme exhaustion associated with paroxysms of high FEVER; SWEATING; shaking CHILLS; and ANEMIA. Malaria in ANIMALS is caused by other species of plasmodia.		02.4620
Plasmodium falciparum Malaria
[description not available]		02.5520
Malaria, Falciparum
Malaria caused by PLASMODIUM FALCIPARUM. This is the severest form of malaria and is associated with the highest levels of parasites in the blood. This disease is characterized by irregularly recurring febrile paroxysms that in extreme cases occur with acute cerebral, renal, or gastrointestinal manifestations.		02.5520
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