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
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
DescriptionSources: http://adisinsight.springer.com/drugs/800010536Curator's Comment: Description was created based on several sources, including
https://www.ncbi.nlm.nih.gov/pubmed/12481191
Sources: http://adisinsight.springer.com/drugs/800010536
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
Sources: http://adisinsight.springer.com/drugs/800010536
Curator's Comment: # Bristol-Myers Squibb
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2111364 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11283675 |
352.0 nM [EC50] | ||
Target ID: CHEMBL3576 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11378159 |
2.4 µM [EC50] | ||
Target ID: CHEMBL2925 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11890900 |
2.4 µM [EC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
0.38% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11745906 |
FLINDOKALNER plasma | Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN |
Doses
Dose | Population | Adverse 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
AE | Significance | Dose | Population |
---|---|---|---|
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
Title | Date | PubMed |
---|---|---|
KCNQ4 channels expressed in mammalian cells: functional characteristics and pharmacology. | 2001 Apr |
|
KCNQ4 channel activation by BMS-204352 and retigabine. | 2001 Jun |
|
BMS-204352 (Bristol Myers Squibb). | 2001 Jun |
|
Activation of KCNQ5 channels stably expressed in HEK293 cells by BMS-204352. | 2002 Feb 22 |
|
BMS-204352: a potassium channel opener developed for the treatment of stroke. | 2002 Winter |
|
Effects of neuronal Kv7 potassium channel activators on hyperactivity in a rodent model of mania. | 2009 Mar 17 |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/12481191
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/14569058
∼1-100 μM Flindokalner (BMS 204352) dose-dependently increased CK2 activity in SK-N-SH cells in the presence of TNF-α
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Classification Tree | Code System | Code | ||
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FDA ORPHAN DRUG |
497515
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NCI_THESAURUS |
C1509
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EU-Orphan Drug |
EU/3/14/1334
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SUB195646
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DTXSID70870176
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187523-35-9
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C76778
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J57O328W4W
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8182
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100000181839
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CHEMBL266510
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214350
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