1-PHENYL-3-PYRAZOLIDINONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C9H10N2O
Molecular Weight	162.1885
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C1CCN(N1)C2=CC=CC=C2

InChI

InChIKey=CMCWWLVWPDLCRM-UHFFFAOYSA-N

InChI=1S/C9H10N2O/c12-9-6-7-11(10-9)8-4-2-1-3-5-8/h1-5H,6-7H2,(H,10,12)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/8427662 | https://www.ncbi.nlm.nih.gov/pubmed/18760329 | https://www.ncbi.nlm.nih.gov/pubmed/15722060

1-Phenyl-3-pyrazolidinone (phenidone) is a dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LOX). Phenidone inhibits both the LO (lipoxygenase) and Cox (cyclooxygenase) pathways, the synthesis of Fos-related antigen protein, and is described as an anti-inflammatory and anti-oxidant compound. Phenidone is a potent hypotensive agent in the spontaneously hypertensive rat. Phenidone was also the best in suppressing LPS induced neurotoxicity, where the more potent neuroprotection by phenidone may be attributable to the synergistic effects of dual COX and LOX inhibition. Therefore, dual inhibitors of COX and LOX, such as phenidone, represent valuable candidates for the development of novel drugs for inflammation-related neurodegenerative disorders including PD.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Cyclooxygenase 89 Target ID: CHEMBL2095157 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15652362 \| https://www.ncbi.nlm.nih.gov/pubmed/15722060	Inhibitor 8504	3.0 µM [IC50]
Arachidonate 12-lipoxygenase 4 Target ID: CHEMBL3687 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8831760	Inhibitor 8504	100.0 nM [IC50]
Arachidonate 5-lipoxygenase 52 Target ID: CHEMBL215 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8831760	Inhibitor 8504	300.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 575 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8427662 https://www.ncbi.nlm.nih.gov/pubmed/1550666	Primary		Preclinical	Unknown Approved Use Unknown
Parkinson's disease 232 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18760329	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Eicosanoids mediate hemolymph oxidative and antioxidative response in larvae of Galleria mellonella L.	2010-06	20138233
The role of jasmonates in floral nectar secretion.	2010-02-19	20174464
Involvement of lipoxygenase in elicitor-stimulated sanguinarine accumulation in Papaver somniferum suspension cultures.	2010-02-13	20829053
Inhibition of lipoxygenase affects induction of both direct and indirect plant defences against herbivorous insects.	2010-02	19806367
Eicosanoids mediate nodulation reactions to a mollicute bacterium in larvae of the blowfly, Chrysomya megacephala.	2009-03	19071132
Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity.	2008-11-07	18760329
Activity of the lipoxygenase inhibitor 1-phenyl-3-pyrazolidinone (phenidone) and derivatives on the inhibition of adhesion molecule expression on human umbilical vascular endothelial cells.	2008-03	19707438
The role of arachidonic acid and its metabolites in insulin secretion from human islets of langerhans.	2007-01	17192482
Eicosanoid biosynthesis inhibitors influence mortality of Pieris brassicae larvae co-injected with fungal conidia.	2006-11	17048247
Case report: Hydroquinone and/or glutaraldehyde induced acute myeloid leukaemia?	2006-07-26	16872480
Binding investigation of human 5-lipoxygenase with its inhibitors by SPR technology correlating with molecular docking simulation.	2006-04	16672272
Anti-inflammatory and anti-oxidant activity of a new class of phenyl-pyrazolone derivatives.	2006-03	16712464
Synthesis and biological evaluation of a new class of acyl derivatives of 3-amino-1-phenyl-4,5-dihydro-1H-pyrazol-5-one as potential dual cyclooxygenase (COX-1 and COX-2) and human lipoxygenase (5-LOX) inhibitors.	2005-04	15848208
Phenidone, a dual inhibitor of cyclooxygenases and lipoxygenases, ameliorates rat paralysis in experimental autoimmune encephalomyelitis by suppressing its target enzymes.	2005-02-28	15722060
Topical antiinflammatory effects of the ether extract from Protium kleinii and alpha-amyrin pentacyclic triterpene.	2005-01-10	15659316
Synthesis and biological evaluation of new phenidone analogues as potential dual cyclooxygenase (COX-1 and COX-2) and human lipoxygenase (5-LOX) inhibitors.	2005-01	15652362
Micellar electrokinetic chromatography at low pH with polyelectrolyte-coated capillaries.	2004-07-09	15296406
Evolutionary change from induced to constitutive expression of an indirect plant resistance.	2004-07-08	15241414
Transcriptional activation of Igl, the gene for indole formation in Zea mays: a structure-activity study with elicitor-active N-acyl glutamines from insects.	2004-04	15110684
Molecular mechanism of nucleotide-induced primary granule release in human neutrophils: role for the P2Y2 receptor.	2004-02	14613890
Dual positional specificity and expression of non-traditional lipoxygenase induced by wounding and methyl jasmonate in maize seedlings.	2003-08	14682619
Anti-inflammatory activity of (E)-1-(3,4-dimethoxyphenyl) butadiene from Zingiber cassumunar Roxb.	2003-08	12860299
12-lipoxygenase in opioid-induced delayed cardioprotection: gene array, mass spectrometric, and pharmacological analyses.	2003-04-04	12623876
Toxicity of human monocytic THP-1 cells and microglia toward SH-SY5Y neuroblastoma cells is reduced by inhibitors of 5-lipoxygenase and its activating protein FLAP.	2003-03	12629151
[Lipoxygenase-mediated N-demethylation of pesticides in vitro].	2002-12	14694585
Antioxidant activity of the methanol fraction of Pluchea indica root extract.	2002-06	12112288
Modulation by eicosanoid biosynthesis inhibitors of immune responses by the insect Manduca sexta to the pathogenic fungus Metarhizium anisopliae.	2002-02	12095238
Degradation of medical x-ray film developing wastewaters by advanced oxidation processes.	2001-11	12230167
Eicosanoids act in nodulation reactions to bacterial infections in newly emerged adult honey bees, Apis mellifera, but not in older foragers.	2001-09	11544147
N-Aminoindoline derivatives as inhibitors of 5-lipoxygenase.	2001-03-26	11277534
Signaling pathways involved in the A and B receptor-mediated cortisol secretagogue effect of endothelins in the human adrenal cortex.	2001-03	11179511
Ion channel-forming alamethicin is a potent elicitor of volatile biosynthesis and tendril coiling. Cross talk between jasmonate and salicylate signaling in lima bean.	2001-01	11154344
NRH:quinone oxidoreductase2 (NQO2).	2000-12-01	11154737
A useful method for differential evaluation of anti-inflammatory effects due to cyclooxygenase and 5-lipoxygenase inhibitions in mice.	1994-08	7990266
Effects of some non-steroidal anti-inflammatory drugs and other agents on cyclooxygenase and lipoxygenase activities in some enzyme preparations.	1985-06	3928952

Patents

Sample Use Guides

In Vivo Use Guide

Rats: phenidone (25, 50 or 100 mg/kg) was administered orally five times every 12 h before the injection of KA (10 mg/kg, i.p.).

Route of Administration: Oral

In Vitro Use Guide

Phenidone (3-30 uM) markedly inhibited leukotriene (LT) C4-induced contractions of the isolated guinea-pig trachea in the presence of indomethacin.

Name

Type

Language

1-PHENYL-3-PYRAZOLIDINONE

Systematic Name

English

NSC-30306

Preferred Name

English

1-PHENYL-3-PYRAZOLIDONE

Systematic Name

English

1-PHENYL-3-PYRAZOLIDINONE [MI]

Common Name

English

PHENIDONE

Common Name

English

Code System Code Type Description

EPA CompTox

DTXSID1049433