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

Molecular Formula	C9H10N2O
Molecular Weight	162.1885
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

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 8297	3.0 µM [IC50]
Arachidonate 12-lipoxygenase 4 Target ID: CHEMBL3687 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8831760	Inhibitor 8297	100.0 nM [IC50]
Arachidonate 5-lipoxygenase 49 Target ID: CHEMBL215 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8831760	Inhibitor 8297	300.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hypertension 567 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 226 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18760329	Primary		Preclinical	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Effects of some non-steroidal anti-inflammatory drugs and other agents on cyclooxygenase and lipoxygenase activities in some enzyme preparations.	1985 Jun	3928952
NRH:quinone oxidoreductase2 (NQO2).	2000 Dec 1	11154737
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 Jan	11154344
Signaling pathways involved in the A and B receptor-mediated cortisol secretagogue effect of endothelins in the human adrenal cortex.	2001 Mar	11179511
N-Aminoindoline derivatives as inhibitors of 5-lipoxygenase.	2001 Mar 26	11277534
Degradation of medical x-ray film developing wastewaters by advanced oxidation processes.	2001 Nov	12230167
Eicosanoids act in nodulation reactions to bacterial infections in newly emerged adult honey bees, Apis mellifera, but not in older foragers.	2001 Sep	11544147
[Lipoxygenase-mediated N-demethylation of pesticides in vitro].	2002 Dec	14694585
Modulation by eicosanoid biosynthesis inhibitors of immune responses by the insect Manduca sexta to the pathogenic fungus Metarhizium anisopliae.	2002 Feb	12095238
Antioxidant activity of the methanol fraction of Pluchea indica root extract.	2002 Jun	12112288
12-lipoxygenase in opioid-induced delayed cardioprotection: gene array, mass spectrometric, and pharmacological analyses.	2003 Apr 4	12623876
Dual positional specificity and expression of non-traditional lipoxygenase induced by wounding and methyl jasmonate in maize seedlings.	2003 Aug	14682619
Anti-inflammatory activity of (E)-1-(3,4-dimethoxyphenyl) butadiene from Zingiber cassumunar Roxb.	2003 Aug	12860299
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 Mar	12629151
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 Apr	15110684
Molecular mechanism of nucleotide-induced primary granule release in human neutrophils: role for the P2Y2 receptor.	2004 Feb	14613890
Evolutionary change from induced to constitutive expression of an indirect plant resistance.	2004 Jul 8	15241414
Micellar electrokinetic chromatography at low pH with polyelectrolyte-coated capillaries.	2004 Jul 9	15296406
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 Apr	15848208
Phenidone, a dual inhibitor of cyclooxygenases and lipoxygenases, ameliorates rat paralysis in experimental autoimmune encephalomyelitis by suppressing its target enzymes.	2005 Feb 28	15722060
Synthesis and biological evaluation of new phenidone analogues as potential dual cyclooxygenase (COX-1 and COX-2) and human lipoxygenase (5-LOX) inhibitors.	2005 Jan	15652362
Topical antiinflammatory effects of the ether extract from Protium kleinii and alpha-amyrin pentacyclic triterpene.	2005 Jan 10	15659316
Binding investigation of human 5-lipoxygenase with its inhibitors by SPR technology correlating with molecular docking simulation.	2006 Apr	16672272
Case report: Hydroquinone and/or glutaraldehyde induced acute myeloid leukaemia?	2006 Jul 26	16872480
Anti-inflammatory and anti-oxidant activity of a new class of phenyl-pyrazolone derivatives.	2006 Mar	16712464
Eicosanoid biosynthesis inhibitors influence mortality of Pieris brassicae larvae co-injected with fungal conidia.	2006 Nov	17048247
The role of arachidonic acid and its metabolites in insulin secretion from human islets of langerhans.	2007 Jan	17192482
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 Mar	19707438
Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity.	2008 Nov 7	18760329
Eicosanoids mediate nodulation reactions to a mollicute bacterium in larvae of the blowfly, Chrysomya megacephala.	2009 Mar	19071132
Inhibition of lipoxygenase affects induction of both direct and indirect plant defences against herbivorous insects.	2010 Feb	19806367
Involvement of lipoxygenase in elicitor-stimulated sanguinarine accumulation in Papaver somniferum suspension cultures.	2010 Oct-Nov	20829053

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 19:08:46 GMT 2023` Edited by `admin` on `Fri Dec 15 19:08:46 GMT 2023`
Record UNII	H0U5612P6K
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

1-PHENYL-3-PYRAZOLIDINONE

Systematic Name

English

1-PHENYL-3-PYRAZOLIDONE

Systematic Name

English

1-PHENYL-3-PYRAZOLIDINONE [MI]

Common Name

English

PHENIDONE

Common Name

English

NSC-30306

Code

English

Code System Code Type Description

EPA CompTox

DTXSID1049433