Page last updated: 2024-11-05

apazone

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

Description

Apazone: An anti-inflammatory agent used in the treatment of rheumatoid arthritis. It also has uricosuric properties and has been used to treat gout. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

apazone : A member of the class of benzotriazines that is 1,2-dihydro-1,2,4-benzotriazine bearing a dimethylamino substitutent at position 3 and a methyl substituent at position 7 and in which the nitrogens at positions 1 and 2 are both acylated by a carboxy group of propylmalonic acid. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID26098
CHEMBL ID1565476
CHEBI ID38010
SCHEMBL ID3190
MeSH IDM0001566

Synonyms (100)

Synonym
BPBIO1_001239
smr001233401
MLS002154093
apazone (usan)
prolixan (tn)
D02966
azapropazone (inn)
PRESTWICK2_001003
brn 0623763
azapropazonum [inn-latin]
prolixan 300
nsc 102824
azapropazona [inn-spanish]
apazone [usan]
1h-pyrazolo(1,2-a)(1,2,4)benzotriazine-1,3(2h)-dione, 5-(dimethylamino)-9-methyl-2-propyl-
azapropazon [german]
einecs 236-913-8
CHEBI:38010 ,
1,2-dihydro-3-dimethylamino-7-methyl-1,2-(propylmalonyl)-1,2,4-benzotriazine
5-(dimethylamino)-9-methyl-2-propyl-1h-pyrazolo(1,2-a)(1,2,4)benzotriazine-1,3(2h)-dione
3-dimethylamino-7-methyl-1,2-(n-propylmalonyl)-1,2-dihydro-1,2,4-benzotriazine
PRESTWICK3_001003
NCGC00179297-01
1h-pyrazolo[1,2-a][1,2,4]benzotriazine-1,3(2h)-dione, 5-(dimethylamino)-9-methyl-2-propyl-
5-(dimethylamino)-9-methyl-2-propyl-1h-pyrazolo[1,2-a][1,2,4]benzotriazine-1,3(2h)-dione
5-(dimethylamino)-9-methyl-2-propyl-pyrazolo[1,2-a][1,2,4]benzotriazine-1,3-dione
azapropazon (german)
BSPBIO_001125
5-(dimethylamino)-9-methyl-2-propyl-1h-pyrazolo[1,2,4]benzotriazine-1,3(2h)-dione
ahr 3018
cinnamin
azapropazone
nsc102824
1,2-(propylmalonyl)-1,2,4-benzotriazine
mitrolan
1h-pyrazolo[1,2,4]benzotriazine-1,3(2h)-dione, 5-(dimethylamine)-9-methyl-2-propyl-
13539-59-8
1h-pyrazolo[1,2,4]benzotriazine-1,3(2h)-dione, 5-(dimethylamino)-9-methyl-2-propyl-
rheumox
3-dimethylamino-7-methyl-1,2-dihydro-1,2,4-benzotriazine
mls002703748 ,
sinnamin
apazone
5-(dimethylamino)-9-methyl-2-propyl-1h-pyrazolo[1,2,4]benzotriazine-1,3(2h)dione
3-dimethylamino-7-methyl-1-2-(n-propylmalonyl)-1,2,4-benzotriazine
wln: t b566 bnv evn hn dhj d3 gn1&1 l1
mi 85
azapropazone dihydrate
azapropazonum
ahr-3018
azapropazon
prolixan
azapropazone (anhydrous)
azapropazona
mi-85
xani
prolix
nsc-102824
cinnopropazone
AB00513995
PRESTWICK1_001003
PRESTWICK0_001003
NCIOPEN2_007171
SPBIO_003006
HMS1571I07
5-(dimethylamino)-9-methyl-2-propylpyrazolo[1,2-a][1,2,4]benzotriazine-1,3-dione
HMS2098I07
azapropazone [inn]
unii-k2vot966zi
k2vot966zi ,
CHEMBL1565476
mi-85di
dtxcid6023735
dtxsid6045408 ,
tox21_110569
HMS2231L14
AKOS015914210
HMS3372M10
(+/-)-apazone
apazone [mi]
5-dimethylamino-9-methyl-2-propylpyrazolo(1,2-a)(1,2,4)benzotriazine-1,3(2h)-dione
azapropazone [who-dd]
azapropazone [mart.]
apazone, (+/-)-
CCG-221003
SCHEMBL3190
1,2-dihydro-3-(dimethylamino)-7-methyl-1,2-(propylmalonyl)-1,2,4-benzotriazine
apazone dihydrate (salt/mix)
1h-pyrazolo(1,2-a)(1,2,4)benzotriazine-1,3(2h)-dione, 5-(dimethylamine)-9-methyl-2-propyl-
MPHPHYZQRGLTBO-UHFFFAOYSA-N
tolyprin (salt/mix)
sr-01000838825
SR-01000838825-2
HMS3715I07
Q368222
ahr-3018;nsc-102824;nsc102824;
NCGC00179297-04
5-(dimethylamino)-9-methyl-2-propyl-1h-benzo[e]pyrazolo[1,2-a][1,2,4]triazine-1,3(2h)-dione
CS-0065495
HY-116442

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" The half-life of the beta-phase was 13."( Pharmacokinetics of azapropazone following single oral and intravenous doses.
Breuing, KH; Gilfrich, HJ; Jähnchen, E; Meinertz, T, 1979
)
0.26
"The pharmacology and pharmacokinetic properties of azapropazone, a new anti-inflammatory analgesic, are reviewed."( The pharmacology and pharmacokinetics of azapropazone - a review.
Jones, CJ, 1976
)
0.26
" Elimination half-life was prolonged but the difference did not reach statistical significance due to the wide variation of the values in the elderly."( Pharmacokinetics of azapropazone in the elderly.
Jones, CJ; Perera, WN; Ritch, AE, 1982
)
0.26
"The pharmacokinetic profile of azapropazone (Prolixan), sodium salt of 5-dimethylamino-9,5-dimethylamine-9-methyl-5-propyl-1H-pyrazolol[1,2-a][1,2,4]benzotriazine-1,3(2H)-dione, was established."( [Human pharmacokinetics of different i.v. doses of azapropazone (HPLC-determination) (author's transl)].
Gikalov, I; Kaufmann, R; Schuster, O, 1982
)
0.26
" pharmacokinetic data on 670 drugs representing, to our knowledge, the largest publicly available set of human clinical pharmacokinetic data."( Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
Lombardo, F; Obach, RS; Waters, NJ, 2008
)
0.35

Compound-Compound Interactions

ExcerptReferenceRelevance
" Brief information on the following reports of drug-drug interactions is given in this article with the intention of giving these reports wider publicity and, possibly, encouraging further observation and research to establish or disprove their validity in a larger and wider range of patients or volunteer subjects."( Early reports on drug interactions.
D'Arcy, PF, 1983
)
0.27

Bioavailability

ExcerptReferenceRelevance
" The bioavailability of azapropazone when administered as capsules was 83 +/- 19%."( Pharmacokinetics of azapropazone following single oral and intravenous doses.
Breuing, KH; Gilfrich, HJ; Jähnchen, E; Meinertz, T, 1979
)
0.26
" The encapsulated particles showed higher dissolution rate and bioavailability but lower ulcerogenic activity as compared with the drug alone."( A new approach to encapsulating non-steroidal anti-inflammatory drugs. V. Biopharmaceutical study of microcapsules of azapropazone coated with pectin and rutin.
el-Dien, EZ; Luzzi, LA; Meshali, MM; Omar, SA,
)
0.13
"Studies were performed in fasted rats to establish if the propensity of 4 non-steroidal anti-inflammatory (NSAI) drugs to elicit varying degrees of gastric mucosal damage following oral administration is related to their rate of absorption by the mucosal and subsequent inhibitory effects on prostaglandin (PG) production in vivo."( Comparative effects of some non-steroidal anti-inflammatory drugs on the ultrastructural integrity and prostaglandin levels in the rat gastric mucosa: relationship to drug uptake.
Fox, SA; Osborne, DJ; Rainsford, KD, 1984
)
0.27
" The procedure has been used successfully in single-dose pharmacokinetic and bioavailability studies of azapropazone dosage forms."( The determination of azapropazone and its 6-hydroxy metabolite in plasma and urine by HPLC.
Beightol, LA; Kline, BJ; Wood, JH, 1983
)
0.27
"The ATP-binding cassette transporter P-glycoprotein (P-gp) is known to limit both brain penetration and oral bioavailability of many chemotherapy drugs."( A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
Ambudkar, SV; Brimacombe, KR; Chen, L; Gottesman, MM; Guha, R; Hall, MD; Klumpp-Thomas, C; Lee, OW; Lee, TD; Lusvarghi, S; Robey, RW; Shen, M; Tebase, BG, 2019
)
0.51

Dosage Studied

ExcerptRelevanceReference
" Initial dosage was 1200 mg."( Long-term use of azapropazone in rheumatoid conditions.
Thune, S, 1976
)
0.26
") failed to elicit mucosal damage either ultrastructurally or even visually up to 23 h after dosing and did not affect the content of PG's even though the drug was present in the mucosa in sufficient concentration to elicit reduction in prostaglandin synthesis in vitro."( Comparative effects of some non-steroidal anti-inflammatory drugs on the ultrastructural integrity and prostaglandin levels in the rat gastric mucosa: relationship to drug uptake.
Fox, SA; Osborne, DJ; Rainsford, KD, 1984
)
0.27
" The aim of the present study was to extend these observations, by examining the dose-response and to compare the uricosuric effect of azapropazone with that of probenecid."( The uricosuric action of azapropazone: dose-response and comparison with probenecid.
Higgens, CS; Scott, JT, 1984
)
0.27
" The procedure has been used successfully in single-dose pharmacokinetic and bioavailability studies of azapropazone dosage forms."( The determination of azapropazone and its 6-hydroxy metabolite in plasma and urine by HPLC.
Beightol, LA; Kline, BJ; Wood, JH, 1983
)
0.27
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
uricosuric drugA gout suppressant that acts directly on the renal tubule to increase the excretion of uric acid, thus reducing its concentrations in plasma.
non-steroidal anti-inflammatory drugAn anti-inflammatory drug that is not a steroid. In addition to anti-inflammatory actions, non-steroidal anti-inflammatory drugs have analgesic, antipyretic, and platelet-inhibitory actions. They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (1)

ClassDescription
benzotriazinesCompounds based on a fused triazine and benzene ring skeleton.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (10)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Chain A, JmjC domain-containing histone demethylation protein 3AHomo sapiens (human)Potency79.43280.631035.7641100.0000AID504339
thioredoxin reductaseRattus norvegicus (Norway rat)Potency70.79460.100020.879379.4328AID588453
ATAD5 protein, partialHomo sapiens (human)Potency17.78280.004110.890331.5287AID504467
thioredoxin glutathione reductaseSchistosoma mansoniPotency44.66840.100022.9075100.0000AID485364
estrogen nuclear receptor alphaHomo sapiens (human)Potency13.05150.000229.305416,493.5996AID743080; AID743091
bromodomain adjacent to zinc finger domain 2BHomo sapiens (human)Potency89.12510.707936.904389.1251AID504333
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency3.54810.035520.977089.1251AID504332
cytochrome P450, family 19, subfamily A, polypeptide 1, isoform CRA_aHomo sapiens (human)Potency9.02260.001723.839378.1014AID743083
chromobox protein homolog 1Homo sapiens (human)Potency100.00000.006026.168889.1251AID540317
transcriptional regulator ERG isoform 3Homo sapiens (human)Potency11.22020.794321.275750.1187AID624246
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Bioassays (44)

Assay IDTitleYearJournalArticle
AID1346987P-glycoprotein substrates identified in KB-8-5-11 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID1296008Cytotoxic Profiling of Annotated Libraries Using Quantitative High-Throughput Screening2020SLAS discovery : advancing life sciences R & D, 01, Volume: 25, Issue:1
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening.
AID651635Viability Counterscreen for Primary qHTS for Inhibitors of ATXN expression
AID1346986P-glycoprotein substrates identified in KB-3-1 adenocarcinoma cell line, qHTS therapeutic library screen2019Molecular pharmacology, 11, Volume: 96, Issue:5
A High-Throughput Screen of a Library of Therapeutics Identifies Cytotoxic Substrates of P-glycoprotein.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588501High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Lethal Factor Protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID1745845Primary qHTS for Inhibitors of ATXN expression
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588497High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain F protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Current protocols in cytometry, Oct, Volume: Chapter 13Microsphere-based flow cytometry protease assays for use in protease activity detection and high-throughput screening.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2006Cytometry. Part A : the journal of the International Society for Analytical Cytology, May, Volume: 69, Issue:5
Microsphere-based protease assays and screening application for lethal factor and factor Xa.
AID588499High-throughput multiplex microsphere screening for inhibitors of toxin protease, specifically Botulinum neurotoxin light chain A protease, MLPCN compound set2010Assay and drug development technologies, Feb, Volume: 8, Issue:1
High-throughput multiplex flow cytometry screening for botulinum neurotoxin type a light chain protease inhibitors.
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1079931Moderate liver toxicity, defined via clinical-chemistry results: ALT or AST serum activity 6 times the normal upper limit (N) or alkaline phosphatase serum activity of 1.7 N. Value is number of references indexed. [column 'BIOL' in source]
AID1079948Times to onset, minimal and maximal, observed in the indexed observations. [column 'DELAI' in source]
AID588220Literature-mined public compounds from Kruhlak et al phospholipidosis modelling dataset2008Toxicology mechanisms and methods, , Volume: 18, Issue:2-3
Development of a phospholipidosis database and predictive quantitative structure-activity relationship (QSAR) models.
AID1079946Presence of at least one case with successful reintroduction. [column 'REINT' in source]
AID1079940Granulomatous liver disease, proven histopathologically. Value is number of references indexed. [column 'GRAN' in source]
AID540213Half life in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079949Proposed mechanism(s) of liver damage. [column 'MEC' in source]
AID1079939Cirrhosis, proven histopathologically. Value is number of references indexed. [column 'CIRRH' in source]
AID1079932Highest frequency of moderate liver toxicity observed during clinical trials, expressed as a percentage. [column '% BIOL' in source]
AID540212Mean residence time in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID540209Volume of distribution at steady state in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079936Choleostatic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is < 2 (see ACUTE). Value is number of references indexed. [column 'CHOLE' in source]
AID540211Fraction unbound in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079933Acute liver toxicity defined via clinical observations and clear clinical-chemistry results: serum ALT or AST activity > 6 N or serum alkaline phosphatases activity > 1.7 N. This category includes cytolytic, choleostatic and mixed liver toxicity. Value is
AID1079934Highest frequency of acute liver toxicity observed during clinical trials, expressed as a percentage. [column '% AIGUE' in source]
AID1079944Benign tumor, proven histopathologically. Value is number of references indexed. [column 'T.BEN' in source]
AID1079941Liver damage due to vascular disease: peliosis hepatitis, hepatic veno-occlusive disease, Budd-Chiari syndrome. Value is number of references indexed. [column 'VASC' in source]
AID1079947Comments (NB not yet translated). [column 'COMMENTAIRES' in source]
AID540210Clearance in human after iv administration2008Drug metabolism and disposition: the biological fate of chemicals, Jul, Volume: 36, Issue:7
Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds.
AID1079945Animal toxicity known. [column 'TOXIC' in source]
AID1079943Malignant tumor, proven histopathologically. Value is number of references indexed. [column 'T.MAL' in source]
AID1079935Cytolytic liver toxicity, either proven histopathologically or where the ratio of maximal ALT or AST activity above normal to that of Alkaline Phosphatase is > 5 (see ACUTE). Value is number of references indexed. [column 'CYTOL' in source]
AID1079942Steatosis, proven histopathologically. Value is number of references indexed. [column 'STEAT' in source]
AID1079938Chronic liver disease either proven histopathologically, or through a chonic elevation of serum amino-transferase activity after 6 months. Value is number of references indexed. [column 'CHRON' in source]
AID1079937Severe hepatitis, defined as possibly life-threatening liver failure or through clinical observations. Value is number of references indexed. [column 'MASS' in source]
AID588519A screen for compounds that inhibit viral RNA polymerase binding and polymerization activities2011Antiviral research, Sep, Volume: 91, Issue:3
High-throughput screening identification of poliovirus RNA-dependent RNA polymerase inhibitors.
AID540299A screen for compounds that inhibit the MenB enzyme of Mycobacterium tuberculosis2010Bioorganic & medicinal chemistry letters, Nov-01, Volume: 20, Issue:21
Synthesis and SAR studies of 1,4-benzoxazine MenB inhibitors: novel antibacterial agents against Mycobacterium tuberculosis.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (174)

TimeframeStudies, This Drug (%)All Drugs %
pre-1990132 (75.86)18.7374
1990's28 (16.09)18.2507
2000's5 (2.87)29.6817
2010's7 (4.02)24.3611
2020's2 (1.15)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 (%)
Trials39 (21.55%)5.53%
Reviews10 (5.52%)6.00%
Case Studies22 (12.15%)4.05%
Observational0 (0.00%)0.25%
Other110 (60.77%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]