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Details

Stereochemistry ACHIRAL
Molecular Formula C23H20FN3O2
Molecular Weight 389.4222
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SL-651498

SMILES

CN1C2=CC=C(F)C=C2C3=C1C(=O)N(C=C3C(=O)N4CCCC4)C5=CC=CC=C5

InChI

InChIKey=QQWHWWDIFGNCLV-UHFFFAOYSA-N
InChI=1S/C23H20FN3O2/c1-25-19-10-9-15(24)13-17(19)20-18(22(28)26-11-5-6-12-26)14-27(23(29)21(20)25)16-7-3-2-4-8-16/h2-4,7-10,13-14H,5-6,11-12H2,1H3

HIDE SMILES / InChI
Molecular Formula C23H20FN3O2
Molecular Weight 389.4222
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/12595909 | https://www.ncbi.nlm.nih.gov/pubmed/11454940 | https://en.wikipedia.org/wiki/SL-651,498

SL651498 was identified as a drug development candidate from a research program designed to discover subtype-selective GABA(A) receptor agonists for the treatment of generalized anxiety disorder and muscle spasms. SL651498 displayed high affinity for GABA(A) receptors containing alpha(1) and alpha(2 subunits, and weaker affinity for alpha5-containing GABA(A) receptors, it behaved as a full agonist at recombinant t GABA(A) receptors containing alpha(2) and alpha(3) subunits, and as a partial agonist at recombinant GABA(A) receptors expressing alpha(1) and alpha(5) subunits. It was shown, that SL651498 represented a promising alternative to agents currently used for the treatment of anxiety disorders and muscle spasms without the major side effects seen with classical benzodiazepines).

CNS Activity

Originator

Sanofi
37
Curator's Comment: https://www.ncbi.nlm.nih.gov/pubmed/11454940

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Partial Agonist
290
 17.0 nM [Ki]
Agonist
2678
 73.0 nM [Ki]
Partial Agonist
290
 117.0 nM [Ki]
Partial Agonist
290
 17.0 nM [Ki]
Partial Agonist
290
 215.0 nM [Ki]
Agonist
2678
 80.3 nM [Ki]
Agonist
2678
 73.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Phase II
1132
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
375 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18635696
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SL651498 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
11 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/18635696
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
SL651498 plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
25 mg single, oral
Highest studied dose
Dose: 25 mg
Route: oral
Route: single
Dose: 25 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/18635696
Page: p.628
healthy, ADULT
n = 20
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Population Size: 20
Sources:
https://pubmed.ncbi.nlm.nih.gov/18635696
Page: p.628
Sources:
https://pubmed.ncbi.nlm.nih.gov/18635696
Page: p.628
PubMed

PubMed

TitleDatePubMed
SL651498: an anxioselective compound with functional selectivity for alpha2- and alpha3-containing gamma-aminobutyric acid(A) (GABA(A)) receptors.
2001 Aug
Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site.
2003 Aug
SL651498, a GABAA receptor agonist with subtype-selective efficacy, as a potential treatment for generalized anxiety disorder and muscle spasms.
2003 Spring
Comparative cue generalization profiles of L-838, 417, SL651498, zolpidem, CL218,872, ocinaplon, bretazenil, zopiclone, and various benzodiazepines in chlordiazepoxide and zolpidem drug discrimination.
2006 Mar
Genuine antihyperalgesia by systemic diazepam revealed by experiments in GABAA receptor point-mutated mice.
2009 Feb
Patents

Patents

US6075021 A
1

Sample Use Guides

In Vivo Use Guide
minimal effective dose: 30 to 100 mg/kg
Route of Administration: Other
In Vitro Use Guide
Studies of [3H]flumazenil binding to native rat GABAA receptor subtypes showed that SL651498 was more potent at displacing [3H]flumazenil binding to membranes from cerebellum (Ki = 6.8 nM) and spinal cord (Ki = 12.3 nM) than from hippocampus (Ki = 117 nM).
Substance Class Chemical
Created
by admin
on Sat Dec 16 11:04:58 UTC 2023
Edited
by admin
on Sat Dec 16 11:04:58 UTC 2023
Record UNII
082VH54RF1
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SL-651498
Common Name English
PYRROLIDINE, 1-((6-FLUORO-2,9-DIHYDRO-9-METHYL-1-OXO-2-PHENYL-1H-PYRIDO(3,4-B)INDOL-4-YL)CARBONYL)-
Systematic Name English
1H-PYRIDO(3,4-B)INDOL-1-ONE, 6-FLUORO-2,9-DIHYDRO-9-METHYL-2-PHENYL-4-(1-PYRROLIDINYLCARBONYL)- 6-FLUORO-9-METHYL-2-PHENYL-4-(PYRROLIDINE-1-CARBONYL)PYRIDO(3,4-B)INDOL-1-ONE
Systematic Name English
SL-651,498
Code English
Code System Code Type Description
PUBCHEM
9908378
Created by admin on Sat Dec 16 11:04:58 UTC 2023 , Edited by admin on Sat Dec 16 11:04:58 UTC 2023
PRIMARY
MANUFACTURER PRODUCT INFORMATION
SL-651498
Created by admin on Sat Dec 16 11:04:58 UTC 2023 , Edited by admin on Sat Dec 16 11:04:58 UTC 2023
PRIMARY Sanofi-Synthlabo (Originator), Anxiolytics, PSYCHOPHARMACOLOGIC DRUGS, GABA(A) BZ Site Receptor Agonists and compound synthesis
CAS
205881-86-3
Created by admin on Sat Dec 16 11:04:58 UTC 2023 , Edited by admin on Sat Dec 16 11:04:58 UTC 2023
PRIMARY
EPA CompTox
DTXSID401045803
Created by admin on Sat Dec 16 11:04:58 UTC 2023 , Edited by admin on Sat Dec 16 11:04:58 UTC 2023
PRIMARY
WIKIPEDIA
SL-651,498
Created by admin on Sat Dec 16 11:04:58 UTC 2023 , Edited by admin on Sat Dec 16 11:04:58 UTC 2023
PRIMARY SL-651,498 is an anxiolytic and anticonvulsant drug used in scientific research, with a chemical structure most closely related to .BETA.-carboline derivatives such as abecarnil and gedocarnil. It has similar effects to benzodiazepine drugs, but is structurally distinct and so is classed as a nonbenzodiazepine anxiolytic.
FDA UNII
082VH54RF1
Created by admin on Sat Dec 16 11:04:58 UTC 2023 , Edited by admin on Sat Dec 16 11:04:58 UTC 2023
PRIMARY
Related Record Type Details
GABAA RECEPTOR
TARGET -> AGONIST
SL651498 is a subtype-selective GABAA agonist, which acts as a full agonist at α2 and α3 subtypes, and as a partial agonist at α1 and α5 (although its action at α5 subtypes is much weaker than at the others).
Related Record Type Details
Structure of SL-651498
ACTIVE MOIETY
SL651498 was identified as a drug development candidate from a research program designed to discover subtype-selective GABA(A) receptor agonists for the treatment of generalized anxiety disorder and muscle spasms. The drug displays high affinity for rat native GABA(A) receptors containing alpha(1) (K(i) = 6.8 nM) and alpha(2) (K(i) = 12.3 nM) subunits, and weaker affinity for alpha5-containing GABA(A) receptors (K(i) = 117 nM).
Structure of SL-651498
ACTIVE MOIETY
New benzo analogue under development(2014). Very selective for a2 and a3 it has very small affinities for a1 and virtually none for a5. This is now postulated as the site responsible for physical dependance and early trials are reporting no tolerance/dependance.
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