U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C38H52N6O2.CH4O3S.H2O
Molecular Weight 738.979
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIRILAZAD MESYLATE

SMILES

O.CS(O)(=O)=O.[H][C@@]12C[C@@H](C)[C@H](C(=O)CN3CCN(CC3)C4=CC(=NC(=N4)N5CCCC5)N6CCCC6)[C@@]1(C)CC=C7[C@@]2([H])CCC8=CC(=O)C=C[C@]78C

InChI

InChIKey=NTRLSGIBUFLYST-VFTWSTDHSA-N
InChI=1S/C38H52N6O2.CH4O3S.H2O/c1-26-22-31-29-9-8-27-23-28(45)10-12-37(27,2)30(29)11-13-38(31,3)35(26)32(46)25-41-18-20-43(21-19-41)34-24-33(42-14-4-5-15-42)39-36(40-34)44-16-6-7-17-44;1-5(2,3)4;/h10-12,23-24,26,29,31,35H,4-9,13-22,25H2,1-3H3;1H3,(H,2,3,4);1H2/t26-,29-,31+,35-,37+,38+;;/m1../s1

HIDE SMILES / InChI
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
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 C38H52N6O2
Molecular Weight 624.8585
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: description was created based on several sources, including: http://www.ncbi.nlm.nih.gov/pubmed/10978061 http://www.ukmi.nhs.uk/applications/ndo/record_view_open.asp?newDrugID=2805

Subarachnoid haemorrhage (SAH) following cerebral aneurysm rupture or trauma can result in the induction of secondary ischaemic brain damage via a decrease in microvascular perfusion, a disruption of the blood-brain barrier and consequent vasogenic oedema, and the delayed spasm of the major cerebral arteries (i.e. vasospasm). It is increasingly apparent that oxygen radical-induced, iron-catalyzed lipid peroxidation (LP) within the subarachnoid blood and vascular wall plays a key role in the occurrence of these secondary events. Tirilazad mesylate, is a nonglucocorticoid, 21-aminosteroid, is a potent cytoprotective inhibitor of LP that works by a combination of radical scavenging and membrane stabilizing properties. It has been demonstrated to attenuate the acute and delayed vascular consequences of SAH and to protect the brain against ischaemic insults. Tirilazad mesylate has been proposed to treat acute ischaemic stroke. When tested on animal models, tirilazad protects brain tissue, and reduces brain damage. However, the drug fails to treat, and even worsens a stroke when studied on a human being.

Originator

Pfizer
420
Curator's Comment: # Pfizer

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8297
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Metaanalysis of trials of tirilazad mesylate in aneurysmal SAH.
2001
Reproducibility of measurements of cerebral infarct volume on CT scans.
2001 Feb
Modulation of inflammation by reactive oxygen species: implications for aging and tissue repair.
2001 Jan 1
Tirilazad mesylate improve water immersion stress induced decrease in erythrocyte deformability in the rats.
2001 Jan-Feb
[Cerebral vasospasm after subarachnoid hemorrhage. Current possibilities of prevention and treatment].
2002
Regional differences in patient characteristics, case management, and outcomes in traumatic brain injury: experience from the tirilazad trials.
2002 Sep
Ultrastructural characterization of dissociated embryonic ventral mesencephalic tissue treated with neuroprotectants.
2003
Effects of different steroid treatment on reperfusion-associated production of reactive oxygen species and arrhythmias during coronary surgery.
2003 Jul
Brain trauma.
2003 Jun
Neuroprotection in transient focal cerebral ischemia by combination drug therapy and mild hypothermia: comparison with customary therapeutic regimen.
2003 Jun
Factors associated with the development of vasospasm after planned surgical treatment of aneurysmal subarachnoid hemorrhage.
2003 Oct
Grading of subarachnoid hemorrhage: modification of the world World Federation of Neurosurgical Societies scale on the basis of data for a large series of patients.
2004 Mar
Racial differences in demographics, acute complications, and outcomes in patients with subarachnoid hemorrhage: a large patient series.
2005 Jul
Relationship between 3-month National Institutes of Health Stroke Scale score and dependence in ischemic stroke patients.
2006
Clinical review: Prevention and therapy of vasospasm in subarachnoid hemorrhage.
2007
Subarachnoid clot volume correlates with age, neurological grade, and blood pressure.
2007 Feb
Comparison of treatment effects between animal experiments and clinical trials: systematic review.
2007 Jan 27
The combinations C1 esterase inhibitor with coagulation factor XIII and N-acetylcysteine with tirilazad mesylate reduce the leukocyte adherence in an experimental endotoxemia in rats.
2008
Impact of combined C1 esterase inhibitor/coagulation factor XIII or N-acetylcysteine/tirilazad mesylate administration on leucocyte adherence and cytokine release in experimental endotoxaemia.
2008 Jul-Aug
Role of cytochrome P450 in drug interactions.
2008 Oct 18
Influence of melatonin on cerebrovascular proinflammatory mediators expression and oxidative stress following subarachnoid hemorrhage in rabbits.
2009
Metaanalysis of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage.
2009
Fat and neurosurgery: does obesity affect outcome after intracranial surgery?
2009 Feb
A systematic review of clinical trials of pharmacological interventions for acute ischaemic stroke (1955-2008) that were completed, but not published in full.
2010 Apr 22
Tirilazad for aneurysmal subarachnoid haemorrhage.
2010 Feb 17
Publication bias in reports of animal stroke studies leads to major overstatement of efficacy.
2010 Mar 30
External validity of risk models: Use of benchmark values to disentangle a case-mix effect from incorrect coefficients.
2010 Oct 15
Patents

Patents

05380840
3

Sample Use Guides

In Vivo Use Guide
0.6, 2, or 6 mg/kg per day
Route of Administration: Intravenous
In Vitro Use Guide
After 7 days in vitro, the number of tyrosine hydroxylase-immunopositive, presumed dopamine (DA) neurons was 140% higher in rat cultures treated with 0.3 microM tirilazad mesylate than that in control cultures.
Substance Class Chemical
Created
by admin
on Sat Dec 16 08:53:38 UTC 2023
Edited
by admin
on Sat Dec 16 08:53:38 UTC 2023
Record UNII
HXS259UWKW
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TIRILAZAD MESYLATE
USAN  
USAN  
Official Name English
PREGNA-1,4,9(11)-TRIENE-3,20-DIONE, 21-(4-(2,6-DI-1-PYRROLIDINYL-4-PYRIMIDINYL)-1-PIPERAZINYL)-16-METHYL-, (16.ALPHA.)-, MONOMETHANESULFONATE, MONOHYDRATE
Systematic Name English
PNU 74006F
Code English
TIRILAZAD METHANESULFONATE MONOHYDRATE [MI]
Common Name English
21-(4-(2,6-DI-1-PYRROLIDINYL-4-PYRIMIDINYL)-1-PIPERAZINYL)-16.ALPHA.-METHYLPREGNA-1,4,9(11)-TRIENE-3,20-DIONE MONOMETHANESULPHONATE, HYDRATE
Common Name English
PREGNA-1,4,9(11)-TRIENE-3,20-DIONE, 21-(4-(2,6-DI-1-PYRROLIDINYL-4-PYRIMIDINYL)-1-PIPERAZINYL)-16-METHYL-, (16.ALPHA.)-, MONOMETHANESULFONATE, HYDRATE
Common Name English
TIRILAZAD MESYLATE HYDRATE
Common Name English
Tirilazad mesilate [WHO-DD]
Common Name English
21-[4-(2,6-Di-1-pyrrolidinyl-4-pyrimidinyl)-1-piperazinyl]-16α-methylpregna-1,4,9(11)-triene-3,20-dione monomethanesulfonate, hydrate
Common Name English
PREGNA-1,4,9(11)-TRIENE-3,20-DIONE, 21-(4-(2,6-DI-1-PYRROLIDINYL-4-PYRIMIDINYL)-1-PIPERAZINYL)-16-METHYL-, (16.ALPHA.)-, MONOMETHANESULPHONATE, HYDRATE
Common Name English
U-74006F
Code English
TIRALAZAD MESILATE HYDRATE
Common Name English
TIRILAZAD MESYLATE [USAN]
Common Name English
TIRALAZAD MESYLATE HYDRATE
Common Name English
FREEDOX
Brand Name English
Classification Tree Code System Code
NCI_THESAURUS C211
Created by admin on Sat Dec 16 08:53:39 UTC 2023 , Edited by admin on Sat Dec 16 08:53:39 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL1908849
Created by admin on Sat Dec 16 08:53:39 UTC 2023 , Edited by admin on Sat Dec 16 08:53:39 UTC 2023
PRIMARY
RXCUI
59827
Created by admin on Sat Dec 16 08:53:39 UTC 2023 , Edited by admin on Sat Dec 16 08:53:39 UTC 2023
PRIMARY RxNorm
CAS
149042-61-5
Created by admin on Sat Dec 16 08:53:39 UTC 2023 , Edited by admin on Sat Dec 16 08:53:39 UTC 2023
NON-SPECIFIC STOICHIOMETRY
FDA UNII
HXS259UWKW
Created by admin on Sat Dec 16 08:53:39 UTC 2023 , Edited by admin on Sat Dec 16 08:53:39 UTC 2023
PRIMARY
PUBCHEM
6918013
Created by admin on Sat Dec 16 08:53:39 UTC 2023 , Edited by admin on Sat Dec 16 08:53:39 UTC 2023
PRIMARY
USAN
Z-53
Created by admin on Sat Dec 16 08:53:39 UTC 2023 , Edited by admin on Sat Dec 16 08:53:39 UTC 2023
PRIMARY
EVMPD
SUB04886MIG
Created by admin on Sat Dec 16 08:53:39 UTC 2023 , Edited by admin on Sat Dec 16 08:53:39 UTC 2023
PRIMARY
NCI_THESAURUS
C152659
Created by admin on Sat Dec 16 08:53:39 UTC 2023 , Edited by admin on Sat Dec 16 08:53:39 UTC 2023
PRIMARY
CAS
111793-42-1
Created by admin on Sat Dec 16 08:53:39 UTC 2023 , Edited by admin on Sat Dec 16 08:53:39 UTC 2023
PRIMARY
MERCK INDEX
m10889
Created by admin on Sat Dec 16 08:53:39 UTC 2023 , Edited by admin on Sat Dec 16 08:53:39 UTC 2023
PRIMARY Merck Index
Related Record Type Details
Structure of TIRILAZAD
PARENT -> SALT/SOLVATE
Structure of TIRILAZAD MESYLATE ANHYDROUS
ANHYDROUS->SOLVATE
Related Record Type Details
Structure of TIRILAZAD
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966