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Details

Stereochemistry ABSOLUTE
Molecular Formula C16H10ClF4NO2
Molecular Weight 359.7032
Optical Activity UNSPECIFIED
Defined Stereocenters 1 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FLINDOKALNER

SMILES

COc1ccc(cc1[C@]2(c3ccc(cc3N=C2O)C(F)(F)F)F)Cl

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 359.7032
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

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

Curator's Comment:: # Bristol-Myers Squibb

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
121 ng/mL
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
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
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%
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: Page: p.359
unhealthy, ADULT
Health Status: unhealthy
Condition: stroke
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources: Page: p.359
10 mg single, intravenous
Studied dose
Dose: 10 mg
Route: intravenous
Route: single
Dose: 10 mg
Sources: Page: p.86
healthy, ADULT
n = 8
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Population Size: 8
Sources: Page: p.86
Disc. AE: Taste disturbance...
AEs leading to
discontinuation/dose reduction:
Taste disturbance (12.5%)
Sources: 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: Page: p.86
healthy, ADULT
n = 8
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: UNKNOWN
Population Size: 8
Sources: Page: p.86
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
KCNQ4 channel activation by BMS-204352 and retigabine.
2001 Jun
Activation of KCNQ5 channels stably expressed in HEK293 cells by BMS-204352.
2002 Feb 22
Patents

Sample Use Guides

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
∼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 Sat Jun 26 02:21:53 UTC 2021
Edited
by admin
on Sat Jun 26 02:21:53 UTC 2021
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 Sat Jun 26 02:21:53 UTC 2021 , Edited by admin on Sat Jun 26 02:21:53 UTC 2021
NCI_THESAURUS C1509
Created by admin on Sat Jun 26 02:21:53 UTC 2021 , Edited by admin on Sat Jun 26 02:21:53 UTC 2021
EU-Orphan Drug EU/3/14/1334
Created by admin on Sat Jun 26 02:21:53 UTC 2021 , Edited by admin on Sat Jun 26 02:21:53 UTC 2021
Code System Code Type Description
EVMPD
SUB195646
Created by admin on Sat Jun 26 02:21:53 UTC 2021 , Edited by admin on Sat Jun 26 02:21:53 UTC 2021
PRIMARY
CAS
187523-35-9
Created by admin on Sat Jun 26 02:21:53 UTC 2021 , Edited by admin on Sat Jun 26 02:21:53 UTC 2021
PRIMARY
NCI_THESAURUS
C76778
Created by admin on Sat Jun 26 02:21:53 UTC 2021 , Edited by admin on Sat Jun 26 02:21:53 UTC 2021
PRIMARY
FDA UNII
J57O328W4W
Created by admin on Sat Jun 26 02:21:53 UTC 2021 , Edited by admin on Sat Jun 26 02:21:53 UTC 2021
PRIMARY
INN
8182
Created by admin on Sat Jun 26 02:21:53 UTC 2021 , Edited by admin on Sat Jun 26 02:21:53 UTC 2021
PRIMARY
ChEMBL
CHEMBL266510
Created by admin on Sat Jun 26 02:21:53 UTC 2021 , Edited by admin on Sat Jun 26 02:21:53 UTC 2021
PRIMARY
PUBCHEM
214350
Created by admin on Sat Jun 26 02:21:53 UTC 2021 , Edited by admin on Sat Jun 26 02:21:53 UTC 2021
PRIMARY
Related Record Type Details
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
FECAL
EXCRETED UNCHANGED
URINE
TARGET -> ACTIVATOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC DOSE

INTRAVENOUS ADMINISTRATION

Tmax PHARMACOKINETIC DOSE

INTRAVENOUS ADMINISTRATION