CINCHOPHEN PIPERAZINE

US Previously Marketed

First marketed in 1908

Details

Stereochemistry	ACHIRAL
Molecular Formula	C16H11NO2.C4H10N2
Molecular Weight	335.3996
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C1CNCCN1.OC(=O)C2=CC(=NC3=C2C=CC=C3)C4=CC=CC=C4

InChI

InChIKey=VGHQOUCHEAXCJT-UHFFFAOYSA-N

InChI=1S/C16H11NO2.C4H10N2/c18-16(19)13-10-15(11-6-2-1-3-7-11)17-14-9-5-4-8-12(13)14;1-2-6-4-3-5-1/h1-10H,(H,18,19);5-6H,1-4H2

HIDE SMILES / InChI

Molecular Formula	C16H11NO2
Molecular Weight	249.264
Charge	0
Count

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

Molecular Formula	C4H10N2
Molecular Weight	86.1356
Charge	0
Count

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

Description
Sources: http://jamanetwork.com/journals/jama/article-abstract/1156819
Curator's Comment: Description was created based on several sources, including http://www.un.org/esa/coordination/CL12.pdf

Cinchophen, phenylcinchoninic acid, seems to have been discovered in 1887 by Doebner and Gieseke and to have been introduced into medicine under the trade name of atophan in 1908 by Nicolaier and Dohrn. Since that time it has been used extensively for gout as well as for other forms of arthritis and for the relief of pain of all types. Use of Cinchophen in humans ceased in the 1930s due to the discovery that it can cause serious liver damage.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Proto-oncogene c-Fos 8 Target ID: P12841 Gene ID: 314322.0 Gene Symbol: Fos Target Organism: Rattus norvegicus (Rat) Sources: https://www.ncbi.nlm.nih.gov/pubmed/8981440	Activator 1430

Conditions

Condition	Modality	Targets	Highest Phase	Product
Arthritis 89 Sources: https://www.ncbi.nlm.nih.gov/pubmed/14890976	Palliative		Approved 8429	Atophan Approved Use It has been used extensively for gout as well as for other forms of arthritis and for the relief of pain of all types.

Doses

Dose	Population	Adverse events
485.9 mg 3 times / day multiple, oral Dose: 485.9 mg, 3 times / day Route: oral Route: multiple Dose: 485.9 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18741907	unhealthy, 19 years n = 1 Health Status: unhealthy Age Group: 19 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18741907	Other AEs: Jaundice, Nausea... Other AEs: Jaundice Nausea Abdominal pain Sources: https://pubmed.ncbi.nlm.nih.gov/18741907
485.9 mg 1 times / day multiple, oral Dose: 485.9 mg, 1 times / day Route: oral Route: multiple Dose: 485.9 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20778752	unhealthy, 38 years n = 1 Health Status: unhealthy Condition: acute rheumatism Age Group: 38 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20778752	Disc. AE: Jaundice... AEs leading to discontinuation/dose reduction: Jaundice (grade 5) Sources: https://pubmed.ncbi.nlm.nih.gov/20778752
300 mg 1 times / day multiple, oral (mean) Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1679861	unhealthy, 57 - 67 years n = 3 Health Status: unhealthy Condition: gout Age Group: 57 - 67 years Sex: F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/1679861	Disc. AE: Hepatitis... Other AEs: Hepatic failure... AEs leading to discontinuation/dose reduction: Hepatitis (acute, 2 patients) Other AEs: Hepatic failure (severe\|grade 5, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/1679861
0.5 g 1 times / day multiple, oral Dose: 0.5 g, 1 times / day Route: oral Route: multiple Dose: 0.5 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13470708	unhealthy, 59 years n = 1 Health Status: unhealthy Age Group: 59 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13470708	Disc. AE: Hepatitis, Agranulocytosis... AEs leading to discontinuation/dose reduction: Hepatitis Agranulocytosis Sources: https://pubmed.ncbi.nlm.nih.gov/13470708

AEs

AE	Significance	Dose	Population
Abdominal pain		485.9 mg 3 times / day multiple, oral Dose: 485.9 mg, 3 times / day Route: oral Route: multiple Dose: 485.9 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18741907	unhealthy, 19 years n = 1 Health Status: unhealthy Age Group: 19 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18741907
Jaundice		485.9 mg 3 times / day multiple, oral Dose: 485.9 mg, 3 times / day Route: oral Route: multiple Dose: 485.9 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18741907	unhealthy, 19 years n = 1 Health Status: unhealthy Age Group: 19 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18741907
Nausea		485.9 mg 3 times / day multiple, oral Dose: 485.9 mg, 3 times / day Route: oral Route: multiple Dose: 485.9 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/18741907	unhealthy, 19 years n = 1 Health Status: unhealthy Age Group: 19 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18741907
Jaundice	grade 5 Disc. AE	485.9 mg 1 times / day multiple, oral Dose: 485.9 mg, 1 times / day Route: oral Route: multiple Dose: 485.9 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/20778752	unhealthy, 38 years n = 1 Health Status: unhealthy Condition: acute rheumatism Age Group: 38 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/20778752
Hepatitis	acute, 2 patients Disc. AE	300 mg 1 times / day multiple, oral (mean) Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1679861	unhealthy, 57 - 67 years n = 3 Health Status: unhealthy Condition: gout Age Group: 57 - 67 years Sex: F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/1679861
Hepatic failure	severe\|grade 5, 1 patient	300 mg 1 times / day multiple, oral (mean) Dose: 300 mg, 1 times / day Route: oral Route: multiple Dose: 300 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/1679861	unhealthy, 57 - 67 years n = 3 Health Status: unhealthy Condition: gout Age Group: 57 - 67 years Sex: F Population Size: 3 Sources: https://pubmed.ncbi.nlm.nih.gov/1679861
Agranulocytosis	Disc. AE	0.5 g 1 times / day multiple, oral Dose: 0.5 g, 1 times / day Route: oral Route: multiple Dose: 0.5 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13470708	unhealthy, 59 years n = 1 Health Status: unhealthy Age Group: 59 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13470708
Hepatitis	Disc. AE	0.5 g 1 times / day multiple, oral Dose: 0.5 g, 1 times / day Route: oral Route: multiple Dose: 0.5 g, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/13470708	unhealthy, 59 years n = 1 Health Status: unhealthy Age Group: 59 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/13470708

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
UGT1A1 204 UGT1A3 84 MRP2 383 OATP1B1 788	UGT1A1 418 UGT1A3 422

Drug as perpetrator

Target	Modality	Activity
MRP2 475	inhibitor 3277 Sources: https://www.sygnaturediscovery.com/publications/posters/deciphering-mechanism-cinchophen-induced-liver-injury/	no
OATP1B1 803	inhibitor 3277 Sources: https://www.sygnaturediscovery.com/publications/posters/deciphering-mechanism-cinchophen-induced-liver-injury/	no
UGT1A1 254	inhibitor 3277 Sources: https://www.sygnaturediscovery.com/publications/posters/deciphering-mechanism-cinchophen-induced-liver-injury/	weak [IC50 3000 uM]
UGT1A3 93	inhibitor 3277 Sources: https://www.sygnaturediscovery.com/publications/posters/deciphering-mechanism-cinchophen-induced-liver-injury/	weak [IC50 3100 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
UGT1A1 418	substrate 3367 Sources: https://www.sygnaturediscovery.com/publications/posters/deciphering-mechanism-cinchophen-induced-liver-injury/	yes
UGT1A3 422	substrate 3367 Sources: https://www.sygnaturediscovery.com/publications/posters/deciphering-mechanism-cinchophen-induced-liver-injury/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChemIDplus	855165138	https://chem.nlm.nih.gov/chemidplus/id/0855165138
EPA DSSTox	DTXSID40234726	https://comptox.epa.gov/dashboard/DTXSID40234726
PubChem	71300650	https://pubchem.ncbi.nlm.nih.gov/compound/71300650
Wikidata	Q27285387

PubMed

Title	Date	PubMed
A series of quinoline analogues as potent inhibitors of C. albicans prolyl tRNA synthetase.	2001 Feb 26	11229766
Synthesis of brequinar analogue inhibitors of malaria parasite dihydroorotate dehydrogenase.	2005 Mar 15	15727850
Comprehensive screening and quantification of veterinary drugs in milk using UPLC-ToF-MS.	2008 Jul	18491081
Poly[bis-(μ-hemihydrogen 2-phenyl-quinoline-4-carboxyl-ato-κN,O)silver(I)].	2009 Jan 23	21581814
Bis(μ-2-phenyl-quinoline-4-carboxyl-ato)-κO,O':O;κO:O,O'-bis-[(2,2'-bipyridine-κN,N')(2-phenyl-quinoline-4-carboxyl-ato-κO,O')cadmium(II)].	2010 Dec 4	21522597
A correlation between the in vitro drug toxicity of drugs to cell lines that express human P450s and their propensity to cause liver injury in humans.	2014 Jan	24085192

Patents

Sample Use Guides

In Vivo Use Guide

The mean dose was 300 mg/day for a mean duration of 3-4 months

Route of Administration: Unknown

In Vitro Use Guide

Cinchophen (200 ug /ml) reduced the response of the isolated guinea-pig ileum to bradykinin.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 17:47:06 GMT 2023` Edited by `admin` on `Fri Dec 15 17:47:06 GMT 2023`
Record UNII	O65C9QHG6D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

CINCHOPHEN PIPERAZINE

Common Name

English

Cinchophen piperazine [WHO-DD]

Common Name

English

4-QUINOLINECARBOXYLIC ACID, 2-PHENYL-, COMPD. WITH PIPERAZINE (1:1)

Common Name

English

Code System Code Type Description

EVMPD

SUB01308MIG