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Details

Stereochemistry ACHIRAL
Molecular Formula C32H32N4O3.ClH
Molecular Weight 557.082
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of SB 224289 HYDROCHLORIDE

SMILES

Cl.CN1CCC2(COC3=CC4=C(C=C23)N(CC4)C(=O)C5=CC=C(C=C5)C6=C(C)C=C(C=C6)C7=NOC(C)=N7)CC1

InChI

InChIKey=GKGKBZYMDILCOF-UHFFFAOYSA-N
InChI=1S/C32H32N4O3.ClH/c1-20-16-25(30-33-21(2)39-34-30)8-9-26(20)22-4-6-23(7-5-22)31(37)36-13-10-24-17-29-27(18-28(24)36)32(19-38-29)11-14-35(3)15-12-32;/h4-9,16-18H,10-15,19H2,1-3H3;1H

HIDE SMILES / InChI
Molecular Formula ClH
Molecular Weight 36.461
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE
Molecular Formula C32H32N4O3
Molecular Weight 520.6215
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

SB-224289 was originally developed by SmithKline, now known as GlaxoSmithKline. It was identified as an antagonist of the 5-hydroxytryptamine receptor 1B (5-HT1B) and subsequently investigated for potential antidepressant activity, although no human trials have been reported. Interestingly, SB-224289 was also found to exhibit antagonistic activity for the antifungal mechanism of Marine Depsipeptide Papuamide A in Candida albicans; although the specific mechanism of action remains unknown.

CNS Activity

CNS Active
3913
Curator's Comment: referenced study was conducted in guinea pig

Originator

SmithKline
6
Curator's Comment: SmithKline Beecham has merged with Glaxo Wellcome to form GlaxoSmithKline

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
5-hydroxytryptamine receptor 1B
21
Target ID: P28222
Gene ID: 3351.0
Gene Symbol: HTR1B
Target Organism: Homo sapiens (Human)
Inverse Agonist
80
 8.0 null [pKi]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Preclinical
Unknown

Approved Use

Unknown
Primary
Basic research
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
The selective 5-HT1B receptor inverse agonist 1'-methyl-5-[[2'-methyl-4'-(5-methyl-1,2, 4-oxadiazol-3-yl)biphenyl-4-yl]carbonyl]-2,3,6,7-tetrahydro- spiro[furo[2,3-f]indole-3,4'-piperidine] (SB-224289) potently blocks terminal 5-HT autoreceptor function both in vitro and in vivo.
1998 Apr 9
SB-224289--a novel selective (human) 5-HT1B receptor antagonist with negative intrinsic activity.
1998 Sep
Inverse agonism and constitutive activity as functional correlates of serotonin h5-HT(1B) receptor/G-protein stoichiometry.
2000 Nov
Agonist properties of pindolol at h5-HT1A receptors coupled to mitogen-activated protein kinase.
2001 Jul 13
Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors.
2004 Aug
The role of the 5-HT1D receptor as a presynaptic autoreceptor in the guinea pig.
2004 Jun 16
Donitriptan, but not sumatriptan, inhibits capsaicin-induced canine external carotid vasodilatation via 5-HT1B rather than 5-HT1D receptors.
2006 Sep
Dopamine released from 5-HT terminals is the cause of L-DOPA-induced dyskinesia in parkinsonian rats.
2007 Jul
Effects of 5-HT drugs in prefrontal cortex during memory formation and the ketamine amnesia-model.
2008
Effects of 5-HT in globus pallidus on haloperidol-induced catalepsy in rats.
2009 Apr 17
Patents

Patents

05972951
2
20090076019
7
6515027
2

Sample Use Guides

In Vivo Use Guide
The regulation of extracellular 5-HT1B receptors by SB-224289 was investigated in Guinea pigs which were dosed via intraperitoneal injection at a concentration of 4 mg/kg. SB-224289 had no effect on 5-HT levels in frontal cortex or striatum. In the dentate gyrus SB-224289 significantly increased extracellular 5-HT, reaching maxima of 151+/-19% of basal levels.
Route of Administration: Intraperitoneal
In Vitro Use Guide
Human 5-HT1B and 5-HT1D receptors were stably transfected into the Chinese Hamster Ovary (ACC098) cell line. Competition studies were performed to determine the affinity of SB-224289 at both h5-HT1B and h5-HT1D receptor subtypes. SB-224289 was also equal to or greater than 75 fold selective for the h5-HT1B receptor over the other human 5-HT receptor subtypes exhibiting a pKi of 8 for human 5HT1B.
Substance Class Chemical
Created
by admin
on Sat Dec 16 08:09:17 GMT 2023
Edited
by admin
on Sat Dec 16 08:09:17 GMT 2023
Record UNII
RTX59ZSB74
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
SB 224289 HYDROCHLORIDE
Common Name English
SPIRO(2H-FURO(2,3-F)INDOLE-3(5H),4'-PIPERIDINE), 6,7-DIHYDRO-1'-METHYL-5-((2'-METHYL-4'-(5-METHYL-1,2,4-OXADIAZOL-3-YL)(1,1'-BIPHENYL)-4-YL)CARBONYL)-, MONOHYDROCHLORIDE
Systematic Name English
METHANONE, (2'-METHYL-4'-(5-METHYL-1,2,4-OXADIAZOL-3-YL)(1,1'-BIPHENYL)-4-YL)(2,5,6,7-TETRAHYDRO-1'-METHYLSPIRO(3H-FURO(2,3-F)INDOLE-3,4'-PIPERIDIN)-5-YL)-, HYDROCHLORIDE (1:1)
Systematic Name English
SB-224289A
Code English
SB 224289A
Code English
Code System Code Type Description
FDA UNII
RTX59ZSB74
Created by admin on Sat Dec 16 08:09:17 GMT 2023 , Edited by admin on Sat Dec 16 08:09:17 GMT 2023
PRIMARY
EPA CompTox
DTXSID9042627
Created by admin on Sat Dec 16 08:09:17 GMT 2023 , Edited by admin on Sat Dec 16 08:09:17 GMT 2023
PRIMARY
CAS
180084-26-8
Created by admin on Sat Dec 16 08:09:17 GMT 2023 , Edited by admin on Sat Dec 16 08:09:17 GMT 2023
PRIMARY
PUBCHEM
11226716
Created by admin on Sat Dec 16 08:09:17 GMT 2023 , Edited by admin on Sat Dec 16 08:09:17 GMT 2023
PRIMARY
Related Record Type Details
Structure of SB 224289
PARENT -> SALT/SOLVATE
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