IDALOPIRDINE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C20H19F5N2O
Molecular Weight	398.3697
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC(F)C(F)(F)COC1=CC(CNCCC2=CNC3=C2C=CC(F)=C3)=CC=C1

InChI

InChIKey=YBAWYTYNMZWMMJ-UHFFFAOYSA-N

InChI=1S/C20H19F5N2O/c21-15-4-5-17-14(11-27-18(17)9-15)6-7-26-10-13-2-1-3-16(8-13)28-12-20(24,25)19(22)23/h1-5,8-9,11,19,26-27H,6-7,10,12H2

HIDE SMILES / InChI

Molecular Formula	C20H19F5N2O
Molecular Weight	398.3697
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://adisinsight.springer.com/drugs/800019915
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/20569520 | https://www.ncbi.nlm.nih.gov/pubmed/27039041

Idalopirdine (Lu AE58054) is a Serotonin 6 receptor (5-HT6) antagonist. Idalopirdine exrets good oral bioavailability and robust efficacy in a rat model of cognitive impairment in schizophrenia. In rats idalopirdine potentiates the effects of acetylcholinesterase inhibitor donepezil on two pharmacodynamic biomarkers associated with cognition, i.e. neuronal oscillations and extracellular ACh levels in the hippocampus. Such potentiation could contribute to the procognitive effects of idalopirdine observed in donepezil-treated Alzheimer's disease patients. The compound is being developed by Lundbeck as an adjunctive therapy with acetylcholinesterase inhibitor donepezil, and is in phase III development for the treatment of Alzheimer's disease in multiple countries worldwide. A phase II trial for the treatment of cognitive impairment associated with schizophrenia was conducted; however no recent reports of development for idalopirdine have been identified.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 6 (5-HT6) receptor 45 Target ID: CHEMBL3371 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20569520	Antagonist 2778		0.83 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Alzheimer’s disease 272 Sources: http://adisinsight.springer.com/drugs/800019915	Primary	Phase III 656	Unknown Approved Use Unknown
Schizophrenia 298 Sources: http://adisinsight.springer.com/drugs/800019915	Primary	Phase II 1132	Unknown Approved Use Unknown
Obesity 203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26419385	Primary	Preclinical	Unknown Approved Use Unknown

Doses

Dose	Population	Adverse events
30 mg 3 times / day multiple, oral Studied dose Dose: 30 mg, 3 times / day Route: oral Route: multiple Dose: 30 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25297016 Page: p.1096	unhealthy, ADULT n = 145 Health Status: unhealthy Condition: Alzheimer disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 145 Sources: https://pubmed.ncbi.nlm.nih.gov/25297016 Page: p.1096	Other AEs: Gamma-glutamyltransferase increased, Alanine aminotransferase increased... Other AEs: Gamma-glutamyltransferase increased (10%) Alanine aminotransferase increased (6%) Aspartate aminotransferase increased (4%) Sources: https://pubmed.ncbi.nlm.nih.gov/25297016 Page: p.1096

AEs

AE	Significance	Dose	Population
Gamma-glutamyltransferase increased	10%	30 mg 3 times / day multiple, oral Studied dose Dose: 30 mg, 3 times / day Route: oral Route: multiple Dose: 30 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25297016 Page: p.1096	unhealthy, ADULT n = 145 Health Status: unhealthy Condition: Alzheimer disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 145 Sources: https://pubmed.ncbi.nlm.nih.gov/25297016 Page: p.1096
Aspartate aminotransferase increased	4%	30 mg 3 times / day multiple, oral Studied dose Dose: 30 mg, 3 times / day Route: oral Route: multiple Dose: 30 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25297016 Page: p.1096	unhealthy, ADULT n = 145 Health Status: unhealthy Condition: Alzheimer disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 145 Sources: https://pubmed.ncbi.nlm.nih.gov/25297016 Page: p.1096
Alanine aminotransferase increased	6%	30 mg 3 times / day multiple, oral Studied dose Dose: 30 mg, 3 times / day Route: oral Route: multiple Dose: 30 mg, 3 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25297016 Page: p.1096	unhealthy, ADULT n = 145 Health Status: unhealthy Condition: Alzheimer disease Age Group: ADULT Sex: M+F Food Status: UNKNOWN Population Size: 145 Sources: https://pubmed.ncbi.nlm.nih.gov/25297016 Page: p.1096

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587 substrate 1737	inhibitor 1767	inhibitor 1852 substrate 1217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363678230	inconclusive [IC50 25.929 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.bmj.com/content/360/bmj.k753.full \| https://pubmed.ncbi.nlm.nih.gov/25297011/ \| https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363678230	yes [IC50 0.0477 uM]	yes (co-administration study) Comment: Increased donepezil bioavailability by 10% Sources: https://www.bmj.com/content/360/bmj.k753.full \| https://pubmed.ncbi.nlm.nih.gov/25297011/ \| https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=363678230
CYP3A4 1925	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645841#sid=363678230	yes [IC50 13.4504 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645842#sid=363678230	yes [IC50 9.5221 uM]

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26022777/	major
CYP2D6 1217	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/26022777/	yes

PubMed

Title	Date	PubMed
5-HT6 receptor antagonists as potential therapeutics for cognitive impairment.	2010	20166958
Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats.	2010 Sep	20569520
Synthesis and structure-activity relationship (SAR) of (5,7-disubstituted 3-phenylsulfonyl-pyrazolo[1,5-a]pyrimidin-2-yl)-methylamines as potent serotonin 5-HT(6) receptor (5-HT(6)R) antagonists.	2011 Dec 8	22029285
Novel aza-analogous ergoline derived scaffolds as potent serotonin 5-HT₆ and dopamine D₂ receptor ligands.	2014 Jul 10	24878269
Safety and efficacy of idalopirdine, a 5-HT6 receptor antagonist, in patients with moderate Alzheimer's disease (LADDER): a randomised, double-blind, placebo-controlled phase 2 trial.	2014 Nov	25297016
Serotonin 5-HT6 receptor antagonists for the treatment of cognitive deficiency in Alzheimer's disease.	2014 Sep 11	24850589

Patents

Sample Use Guides

In Vivo Use Guide

Idalopirdine 90 mg per day (30 mg thrice daily) improved cognitive function in donepezil-treated patients with moderate Alzheimer's disease (NCT01019421).

Route of Administration: Oral

In Vitro Use Guide

Unknown

Substance Class	Chemical Created by `admin` on `Fri Dec 15 15:22:47 UTC 2023` Edited by `admin` on `Fri Dec 15 15:22:47 UTC 2023`
Record UNII	59WCJ0YNWM
Record Status	`Validated (UNII)`
Record Version

Download

Name

Type

Language

IDALOPIRDINE

Official Name

English

SGS518

Code

English

LU-AE-58054

Code

English

LY483518

Code

English

LU-AE58054

Code

English

1H-INDOLE-3-ETHANAMINE, 6-FLUORO-N-((3-(2,2,3,3-TETRAFLUOROPROPOXY)PHENYL)METHYL)-

Systematic Name

English

LU AE-58054

Code

English

idalopirdine [INN]

Common Name

English

Idalopirdine [WHO-DD]

Common Name

English

LU AE58054

Code

English

N-(2-(6-FLUORO-1H-INDOL-3-YL)ETHYL)-3-(2,2,3,3-TETRAFLUOROPROPOXY)BENZYLAMINE

Systematic Name

English

SGS-518

Code

English

IDALOPIRDINE [USAN]

Common Name

English

LY-483518

Code

English

Code System Code Type Description

EPA CompTox

DTXSID201026015