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 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
Signaling pathways involved in the A and B receptor-mediated cortisol secretagogue effect of endothelins in the human adrenal cortex.	2001 Mar	11179511
Modulation by eicosanoid biosynthesis inhibitors of immune responses by the insect Manduca sexta to the pathogenic fungus Metarhizium anisopliae.	2002 Feb	12095238
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
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
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 hemolymph oxidative and antioxidative response in larvae of Galleria mellonella L.	2010 Jun	20138233

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

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