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Details

Stereochemistry ACHIRAL
Molecular Formula 2C17H16N6O.2CH4O3S.H2O
Molecular Weight 850.924
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ZONIPORIDE MESYLATE HEMIHYDRATE

SMILES

O.CS(O)(=O)=O.CS(O)(=O)=O.NC(=N)NC(=O)C1=C(C2CC2)N(N=C1)C3=CC=CC4=NC=CC=C34.NC(=N)NC(=O)C5=C(C6CC6)N(N=C5)C7=CC=CC8=NC=CC=C78

InChI

InChIKey=HGNAEEHUNCEYEO-UHFFFAOYSA-N
InChI=1S/2C17H16N6O.2CH4O3S.H2O/c2*18-17(19)22-16(24)12-9-21-23(15(12)10-6-7-10)14-5-1-4-13-11(14)3-2-8-20-13;2*1-5(2,3)4;/h2*1-5,8-10H,6-7H2,(H4,18,19,22,24);2*1H3,(H,2,3,4);1H2

HIDE SMILES / InChI
Molecular Formula C17H16N6O
Molecular Weight 320.3485
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula CH4O3S
Molecular Weight 96.106
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula H2O
Molecular Weight 18.0153
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/11259552 http://www.abcam.com/zoniporide-hydrochloride-ab142012.html

Zoniporide hydrochloride is a novel, potent and selective NHE-1 inhibitor (IC50 = 14 nM). Reduces infarct size in the isolated heart (EC50 = 0.25 nM). Attenuates post-ischemic cardiac contractile dysfunction and ischemia-reperfusion-induced ventricular fibrillation in vivo. Zoniporide hydrochloride represents a novel class of potent and selective human NHE-1 inhibitors with potential utility for providing cardioprotection in a clinical setting.

Originator

Pfizer
420
Curator's Comment: # Pfizer

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
 12000.0 nM [IC50]
Inhibitor
8297
 14.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase II
1132
Unknown

Approved Use

Unknown
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
0.07 μg × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/11277524
1 mg/kg single, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ZONIPORIDE plasma
Rattus norvegicus
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
0.5 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/11277524
1 mg/kg single, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ZONIPORIDE plasma
Rattus norvegicus
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
46%
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/11277524
1 mg/kg single, intravenous
dose: 1 mg/kg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
ZONIPORIDE plasma
Rattus norvegicus
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
unhealthy, ADULT
n = 266
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 266
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
Disc. AE: Hepatic failure, Bilirubin elevated...
Other AEs: Headache, Atrial fibrillation...
AEs leading to
discontinuation/dose reduction:
Hepatic failure (0.8%)
Bilirubin elevated
Vomiting (25.6%)
Other AEs:
Headache (6.4%)
Atrial fibrillation (6.4%)
Tachycardia (10.9%)
Jaundice (2.3%)
Nausea (41.7%)
Elevated liver enzyme levels
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
AEs

AEs

AESignificanceDosePopulation
Elevated liver enzyme levels
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
unhealthy, ADULT
n = 266
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 266
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
Hepatic failure 0.8%
Disc. AE
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
unhealthy, ADULT
n = 266
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 266
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
Tachycardia 10.9%
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
unhealthy, ADULT
n = 266
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 266
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
Jaundice 2.3%
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
unhealthy, ADULT
n = 266
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 266
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
Vomiting 25.6%
Disc. AE
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
unhealthy, ADULT
n = 266
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 266
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
Nausea 41.7%
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
unhealthy, ADULT
n = 266
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 266
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
Atrial fibrillation 6.4%
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
unhealthy, ADULT
n = 266
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 266
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
Headache 6.4%
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
unhealthy, ADULT
n = 266
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 266
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
Bilirubin elevated Disc. AE
12 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 12 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 12 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
unhealthy, ADULT
n = 266
Health Status: unhealthy
Condition: peripheral vascular disease
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Population Size: 266
Sources:
https://pubmed.ncbi.nlm.nih.gov/16202888
Page: p.573
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1587
inhibitor
1767
inhibitor
1852

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1537

AO
16
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
CYP2C9
1819
 no
CYP2D6
1891
 no
CYP3A4
1925
 no
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
P-gp
1537
 no
AO
16
 yes [Km 3.4 uM]
PubMed

PubMed

TitleDatePubMed
An overview of inhibitors of Na(+)/H(+) exchanger.
2003 Jun
Zoniporide: a potent and selective inhibitor of the human sodium-hydrogen exchanger isoform 1 (NHE-1).
2003 Spring
Basolateral Na+-H+ exchanger-1 in rat taste receptor cells is involved in neural adaptation to acidic stimuli.
2004 Apr 1
Initial rate analysis of zoniporide hydrolysis degradants using high-performance liquid chromatography coupled with mass spectrometric detection.
2007
Solute diffusion through stripped mouse duodenum.
2007 Dec
Zoniporide preserves left ventricular compliance during ventricular fibrillation and minimizes postresuscitation myocardial dysfunction through benefits on energy metabolism.
2007 Oct
Does the use of a volatile anesthetic regimen attenuate the incidence of cardiac events after vascular surgery?
2008
Targeting Na+/H+ exchanger regulation for cardiac protection: a RSKy approach?
2008 Apr
Cross-species comparison of the metabolism and excretion of zoniporide: contribution of aldehyde oxidase to interspecies differences.
2010 Apr
Critical role of the STAT3 pathway in the cardioprotective efficacy of zoniporide in a model of myocardial preservation - the rat isolated working heart.
2011 Feb
Patents

Patents

06441176
6
06492401
7
06627643
6
06753334
6
06974813
6
JP2003510331A
14
WO2005079803A1
6

Sample Use Guides

In Vivo Use Guide
Rabbits: 0.25, 1, and 4 mg/kg/h, i.v.
Route of Administration: Intravenous
In Vitro Use Guide
Zoniporide inhibited 22Na(+) uptake in fibroblasts expressing human NHE-1 in a concentration-dependent manner (IC(50) = 14 nM)
Substance Class Chemical
Created
by admin
on Sat Dec 16 01:22:51 UTC 2023
Edited
by admin
on Sat Dec 16 01:22:51 UTC 2023
Record UNII
FW861BH5NA
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ZONIPORIDE MESYLATE HEMIHYDRATE
Common Name English
1H-PYRAZOLE-4-CARBOXAMIDE, N-(AMINOIMINOMETHYL)-5-CYCLOPROPYL-1-(5-QUINOLINYL)-, METHANESULFONATE, HYDRATE (2:2:1)
Common Name English
Code System Code Type Description
PUBCHEM
71300877
Created by admin on Sat Dec 16 01:22:51 UTC 2023 , Edited by admin on Sat Dec 16 01:22:51 UTC 2023
PRIMARY
FDA UNII
FW861BH5NA
Created by admin on Sat Dec 16 01:22:51 UTC 2023 , Edited by admin on Sat Dec 16 01:22:51 UTC 2023
PRIMARY
EPA CompTox
DTXSID20187367
Created by admin on Sat Dec 16 01:22:51 UTC 2023 , Edited by admin on Sat Dec 16 01:22:51 UTC 2023
PRIMARY
CAS
336881-22-2
Created by admin on Sat Dec 16 01:22:51 UTC 2023 , Edited by admin on Sat Dec 16 01:22:51 UTC 2023
PRIMARY
Related Record Type Details
Structure of ZONIPORIDE
PARENT -> SALT/SOLVATE
Structure of ZONIPORIDE MESYLATE
ANHYDROUS->SOLVATE
NIH
NCATS
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