SL-651498

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 Search

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

Description
Sources: https://www.google.com/patents/US6075021https://www.ncbi.nlm.nih.gov/pubmed/11454940
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

Approval Year

Targets

Primary Target	Pharmacology	Potency
GABA-A receptor; alpha-1/beta-2/gamma-2 27 Target ID: CHEMBL2095172 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11454940	Partial Agonist 290	17.0 nM [Ki]
GABA A receptor alpha-2/beta-2/gamma-2 6 Target ID: CHEMBL2111413 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11454940	Agonist 2678	73.0 nM [Ki]
GABA-A receptor; alpha-5/beta-3/gamma-2 14 Target ID: CHEMBL2094122 Sources: https://www.ncbi.nlm.nih.gov/pubmed/11454940	Partial Agonist 290	117.0 nM [Ki]
GABA-A receptor; alpha-1/beta-2/gamma-2 27 Target ID: CHEMBL2095167 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595909	Partial Agonist 290	17.0 nM [Ki]
GABA A receptor alpha-5/beta-3/gamma-2 2 Target ID: CHEMBL2111374 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595909	Partial Agonist 290	215.0 nM [Ki]
GABA A receptor alpha-3/beta-2/gamma-2 4 Target ID: CHEMBL2111343 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595909	Agonist 2678	80.3 nM [Ki]
GABA A receptor alpha-2/beta-2/gamma-2 6 Target ID: CHEMBL2111327 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595909	Agonist 2678	73.0 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Generalized anxiety disorder 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595909	Primary	Preclinical	Unknown Approved Use Unknown
Muscle spasm 40 Sources: https://www.ncbi.nlm.nih.gov/pubmed/12595909	Primary	Preclinical	Unknown Approved Use Unknown
Anxiety 267 Sources: http://mentalhealthdaily.com/2015/02/26/5-new-anxiety-medications-in-development-2015/ https://www.ncbi.nlm.nih.gov/pubmed/12595909	Primary	Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
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

T_1/2

Value	Dose	Co-administered	Analyte	Population
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

Dose	Population	Adverse 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

Title	Date	PubMed
SL651498: an anxioselective compound with functional selectivity for alpha2- and alpha3-containing gamma-aminobutyric acid(A) (GABA(A)) receptors.	2001 Aug	11454940
Anxioselective compounds acting at the GABA(A) receptor benzodiazepine binding site.	2003 Aug	12871032
SL651498, a GABAA receptor agonist with subtype-selective efficacy, as a potential treatment for generalized anxiety disorder and muscle spasms.	2003 Spring	12595909
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	16339395
Genuine antihyperalgesia by systemic diazepam revealed by experiments in GABAA receptor point-mutated mice.	2009 Feb	19091469

Patents

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).

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