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Details

Stereochemistry ABSOLUTE
Molecular Formula C16H10ClF4NO2
Molecular Weight 359.703
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLINDOKALNER

SMILES

COC1=CC=C(Cl)C=C1[C@]2(F)C(=O)NC3=C2C=CC(=C3)C(F)(F)F

InChI

InChIKey=ULYONBAOIMCNEH-HNNXBMFYSA-N
InChI=1S/C16H10ClF4NO2/c1-24-13-5-3-9(17)7-11(13)15(18)10-4-2-8(16(19,20)21)6-12(10)22-14(15)23/h2-7H,1H3,(H,22,23)/t15-/m0/s1

HIDE SMILES / InChI
Molecular Formula C16H10ClF4NO2
Molecular Weight 359.703
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 1 / 1
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/12481191

Flindokalner (BMS 204352; MaxiPost™) is a neuroprotective agent with potential in the treatment of stroke developed by Bristol-Myers Squibb. Flindokalner is a potent and effective opener of two important subtypes of neuronal potassium channels, the calcium-activated, big-conductance potassium channels (K(Ca) channels) and voltage-dependent, non-inactivating potassium channels known as KCNQ channels. Flindokalner significantly reduced cortical infarct volume in a animal models of stroke. Flindokalner failed to show superior efficacy in acute stroke patients compared to placebo in a Phase III study.

CNS Activity

CNS Active
3913
Curator's Comment: Flindokalner (BMS 204352; MaxiPost™) is brain penetrant and active (stroke neuroprotection and anxiolytic) in rodents https://www.ncbi.nlm.nih.gov/pubmed/12214322 https://www.ncbi.nlm.nih.gov/pubmed/11283675 https://www.ncbi.nlm.nih.gov/pubmed/15814569 But Flindokalner is failed to show efficacy in acute stroke patients compared to placebo in a Phase III study. https://www.ncbi.nlm.nih.gov/pubmed/12481191

Originator

Bristol-Myers Squibb
145
Curator's Comment: # Bristol-Myers Squibb

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Opener
34
 352.0 nM [EC50]
Opener
34
 2.4 µM [EC50]
Opener
34
 2.4 µM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
656
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
121 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/15502007
10 mg single, intravenous
dose: 10 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FLINDOKALNER plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
184 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/15502007
10 mg single, intravenous
dose: 10 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FLINDOKALNER plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
37 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/15502007
10 mg single, intravenous
dose: 10 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
FLINDOKALNER plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
0.38%
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/11745906
FLINDOKALNER plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
2 mg/kg 1 times / day multiple, intravenous
Highest studied dose
Dose: 2 mg/kg, 1 times / day
Route: intravenous
Route: multiple
Dose: 2 mg/kg, 1 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/12481191
Page: p.359
unhealthy, ADULT
Health Status: unhealthy
Condition: stroke
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/12481191
Page: p.359
Sources:
https://pubmed.ncbi.nlm.nih.gov/12481191
Page: p.359
10 mg single, intravenous
Studied dose
Dose: 10 mg
Route: intravenous
Route: single
Dose: 10 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/15502007
Page: p.86
healthy, ADULT
n = 8
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/15502007
Page: p.86
Disc. AE: Taste disturbance...
AEs leading to
discontinuation/dose reduction:
Taste disturbance (12.5%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/15502007
Page: p.86
AEs

AEs

AESignificanceDosePopulation
Taste disturbance 12.5%
Disc. AE
10 mg single, intravenous
Studied dose
Dose: 10 mg
Route: intravenous
Route: single
Dose: 10 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/15502007
Page: p.86
healthy, ADULT
n = 8
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Population Size: 8
Sources:
https://pubmed.ncbi.nlm.nih.gov/15502007
Page: p.86
Sourcing

Sourcing

Vendor/AggregatorIDURL
ApexBio Technology
B7722
https://www.apexbt.com/catalogsearch/result/?q=B7722
Axon MedChem
1112
https://www.axonmedchem.com/product/1112
Axon MedChem
1308
https://www.axonmedchem.com/product/1308
BLD Pharm
BD317814
http://www.bldpharm.com/search/Search.html?keyword=BD317814
BOC Sciences
187523-35-9
http://www.bocsci.com/description.asp?cas=187523-35-9
Chem Scene
CS-0029243
http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0029243
MedChem Express
HY-108584
https://www.medchemexpress.com/search.html?q=HY-108584&ft=&fa=&fp=
MolPort
MolPort-035-765-895
https://www.molport.com/shop/molecule-link/MolPort-035-765-895
Molnova
M12907
https://www.molnova.com/en/serch-list.html?keywords=M12907
MuseChem
R036286
https://www.musechem.com/product/R036286.html
Tocris
4949
https://www.tocris.com/search.php?Type=QuickSearch&Value=4949
Toronto Research Chemicals
B595920
https://www.trc-canada.com/product-detail/?CatNum=B595920
Toronto Research Chemicals
B596030
https://www.trc-canada.com/product-detail/?CatNum=B596030
eMolecules
36366916
https://orderbb.emolecules.com/search/#?query=36366916
eMolecules
36367019
https://orderbb.emolecules.com/search/#?query=36367019
mcule
MCULE-3677426981
https://mcule.com/MCULE-3677426981/
PubMed

PubMed

TitleDatePubMed
Targeting acute ischemic stroke with a calcium-sensitive opener of maxi-K potassium channels.
2001 Apr
KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology.
2001 Apr
Effects of neuronal Kv7 potassium channel activators on hyperactivity in a rodent model of mania.
2009 Mar 17
Patents

Patents

06916937
1
20050203089
1
6916937
1
7169803
1
7812177
1

Sample Use Guides

In Vivo Use Guide
In healthy humans, single and multiple i.v. doses of BMS-204352 (0.001 to 0.2 mg/kg) were safe, well-tolerated and without psychomotor function effects. Multiple doses of BMS-204352 (0.1-2 mg/kg i.v.) administered within 48 h after stroke onset were well tolerated in patients in Phase II studies, designed to evaluate safety, tolerability and pharmacokinetics.
Route of Administration: Intravenous
In Vitro Use Guide
∼1-100 μM Flindokalner (BMS 204352) dose-dependently increased CK2 activity in SK-N-SH cells in the presence of TNF-α
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:46:32 UTC 2023
Edited
by admin
on Fri Dec 15 15:46:32 UTC 2023
Record UNII
J57O328W4W
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
FLINDOKALNER
INN   USAN  
USAN   INN  
Official Name English
MAXIPOST
Brand Name English
BMS-204352
Code English
FLINDOKALNER [USAN]
Common Name English
(3S)-3-(5-Chloro-2-methoxyphenyl)-3-fluoro-6-(trifluoromethyl)-1,3-dihydro-2H-indol-2-one
Systematic Name English
flindokalner [INN]
Common Name English
2H-INDOL-2-ONE, 3-(5-CHLORO-2-METHOXYPHENYL)-3-FLUORO-1,3-DIHYDRO-6-(TRIFLUOROMETHYL)-, (3S)-
Systematic Name English
(3S)-(+)-(5-CHLORO-2-METHOXYPHENYL)-1,3-DIHYDRO-3-FLUORO-6-(TRIFLUOROMETHYL)-2H-INDOL-2-ONE
Systematic Name English
BMS-204352-01
Code English
Classification Tree Code System Code
FDA ORPHAN DRUG 497515
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
NCI_THESAURUS C1509
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
EU-Orphan Drug EU/3/14/1334
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
Code System Code Type Description
EVMPD
SUB195646
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
EPA CompTox
DTXSID70870176
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
CAS
187523-35-9
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
NCI_THESAURUS
C76778
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
FDA UNII
J57O328W4W
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
INN
8182
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
USAN
MM-39
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
SMS_ID
100000181839
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
ChEMBL
CHEMBL266510
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
PUBCHEM
214350
Created by admin on Fri Dec 15 15:46:32 UTC 2023 , Edited by admin on Fri Dec 15 15:46:32 UTC 2023
PRIMARY
Related Record Type Details
CYTOCHROME P450 3A4
METABOLIC ENZYME -> SUBSTRATE
Structure of FLINDOKALNER
EXCRETED UNCHANGED
FECAL
Structure of FLINDOKALNER
EXCRETED UNCHANGED
URINE
CALCIUM-ACTIVATED POTASSIUM CHANNEL SUBUNIT ALPHA-1
TARGET -> ACTIVATOR
Related Record Type Details
Structure of .BETA.-D-GLUCOPYRANURONIC ACID, 1-((3S)-3-(5-CHLORO-2-METHOXYPHENYL)-3-FLUORO-2,3-DIHYDRO-2-OXO-6-(TRIFLUOROMETHYL)-1H-INDOL-1-YL)-1-DEOXY-
METABOLITE -> PARENT
PLASMA
Structure of .BETA.-D-GLUCOPYRANURONIC ACID, 1-((3S)-3-(5-CHLORO-2-METHOXYPHENYL)-3-FLUORO-2,3-DIHYDRO-2-OXO-6-(TRIFLUOROMETHYL)-1H-INDOL-1-YL)-1-DEOXY-
METABOLITE -> PARENT
URINE
Related Record Type Details
Structure of FLINDOKALNER
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC DOSE

INTRAVENOUS ADMINISTRATION

Tmax PHARMACOKINETIC DOSE

INTRAVENOUS ADMINISTRATION

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