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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 of IDALOPIRDINE

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
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

Eli Lilly
239
Curator's Comment: # Eli Lilly

Approval Year

Unknown
127998
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2737
 0.83 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
651
Unknown

Approved Use

Unknown
Primary
Phase II
1133
Unknown

Approved Use

Unknown
Primary
Preclinical
Unknown

Approved Use

Unknown
Doses

Doses

DosePopulationAdverse 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

AEs

AESignificanceDosePopulation
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

Overview

CYP3A4CYP2C9CYP2D6hERG
inhibitor
1532

substrate
1670
inhibitor
1695
inhibitor
1789

substrate
1168

OverviewOther

Other InhibitorOther SubstrateOther Inducer
P-gp
1401
Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
P-gp
1588
 inconclusive [IC50 25.929 uM]
CYP2D6
1826
 yes [IC50 0.0477 uM]
CYP3A4
1857
 yes [IC50 13.4504 uM]
CYP2C9
1747
 yes [IC50 9.5221 uM]
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
CYP3A4
1670
 major
CYP2D6
1168
 yes
PubMed

PubMed

TitleDatePubMed
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
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
Serotonin 5-HT6 receptor antagonists for the treatment of cognitive deficiency in Alzheimer's disease.
2014 Sep 11
Patents

Patents

07157488
3
20060009511
3

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 16 16:56:23 UTC 2022
Edited
by admin
on Fri Dec 16 16:56:23 UTC 2022
Record UNII
59WCJ0YNWM
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
IDALOPIRDINE
INN   USAN   WHO-DD  
USAN   INN  
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
Created by admin on Fri Dec 16 16:56:23 UTC 2022 , Edited by admin on Fri Dec 16 16:56:23 UTC 2022
PRIMARY
PUBCHEM
21071390
Created by admin on Fri Dec 16 16:56:23 UTC 2022 , Edited by admin on Fri Dec 16 16:56:23 UTC 2022
PRIMARY
INN
9866
Created by admin on Fri Dec 16 16:56:23 UTC 2022 , Edited by admin on Fri Dec 16 16:56:23 UTC 2022
PRIMARY
ChEMBL
CHEMBL3286580
Created by admin on Fri Dec 16 16:56:23 UTC 2022 , Edited by admin on Fri Dec 16 16:56:23 UTC 2022
PRIMARY
CAS
467459-31-0
Created by admin on Fri Dec 16 16:56:23 UTC 2022 , Edited by admin on Fri Dec 16 16:56:23 UTC 2022
PRIMARY
NCI_THESAURUS
C166835
Created by admin on Fri Dec 16 16:56:23 UTC 2022 , Edited by admin on Fri Dec 16 16:56:23 UTC 2022
PRIMARY
DRUG BANK
DB11957
Created by admin on Fri Dec 16 16:56:23 UTC 2022 , Edited by admin on Fri Dec 16 16:56:23 UTC 2022
PRIMARY
USAN
BC-92
Created by admin on Fri Dec 16 16:56:23 UTC 2022 , Edited by admin on Fri Dec 16 16:56:23 UTC 2022
PRIMARY
WIKIPEDIA
Idalopirdine
Created by admin on Fri Dec 16 16:56:23 UTC 2022 , Edited by admin on Fri Dec 16 16:56:23 UTC 2022
PRIMARY
FDA UNII
59WCJ0YNWM
Created by admin on Fri Dec 16 16:56:23 UTC 2022 , Edited by admin on Fri Dec 16 16:56:23 UTC 2022
PRIMARY
Related Record Type Details
Structure of IDALOPIRDINE HYDROCHLORIDE
SALT/SOLVATE -> PARENT
5-HYDROXYTRYPTAMINE RECEPTOR 6
TARGET -> INHIBITOR
Phase III trials showed weak efficacy as compared to phase II trials, which may be explained by underdosing. Phase II trials evaluated the use of 90 mg daily (30 mg TID) as an adjunct to an acetylcholinesterase inhibitor. Study investigators decided to lower the dose of idalopirdine in phase III trials based on receptor occupancy analysis conducted by PET scan
Related Record Type Details
Structure of IDALOPIRDINE
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