GSK-239512

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H27N3O2
Molecular Weight	377.4794
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

SMILES

O=C1CCCN1C2=CN=C(OC3=CC=C4CCN(CCC4=C3)C5CCC5)C=C2

InChI

InChIKey=YFRBKEVUUCQYOW-UHFFFAOYSA-N

InChI=1S/C23H27N3O2/c27-23-5-2-12-26(23)20-7-9-22(24-16-20)28-21-8-6-17-10-13-25(19-3-1-4-19)14-11-18(17)15-21/h6-9,15-16,19H,1-5,10-14H2

HIDE SMILES / InChI

Molecular Formula	C23H27N3O2
Molecular Weight	377.4794
Charge	0
Count	MOL RATIO 1 MOL RATIO (average)

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

Description

GlaxoSmithKline (GSK) was developing GSK-239512 as a histamine H3 receptor antagonist/inverse agonist as a monotherapy treatment for subjects with mild-to-moderate probable Alzheimer's disease (AD), multiple sclerosis and Schizophrenia. However, in March 2017, GSK globally discontinued the study of GSK-239512 at phase II.

Originator

Approval Year

PubMed

Show entries

Title	Date	PubMed
The safety, tolerability, pharmacokinetics and cognitive effects of GSK239512, a selective histamine H₃ receptor antagonist in patients with mild to moderate Alzheimer's disease: a preliminary investigation.	2013 Mar	23521503
Lesion remyelinating activity of GSK239512 versus placebo in patients with relapsing-remitting multiple sclerosis: a randomised, single-blind, phase II study.	2017 Feb	27888416

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Patents

Sample Use Guides

In Vivo Use Guide

In this 16-week, double-blind, randomized, parallel group study, 196 currently untreated subjects with mild-tomoderate AD (Mini Mental State Examination [MMSE] 16-24) received GSK239512 (n=97); or placebo (n=99) administered orally each morning.

Route of Administration: Oral

Substance Class	Chemical
Record UNII	4I7U5C459M
Record Status	`Validated (UNII)`
Record Version

Show entries

Name

Type

Language

GSK-239512

Common Name

English

GSK-239512A

Code

English

2-PYRROLIDINONE, 1-(6-((3-CYCLOBUTYL-2,3,4,5-TETRAHYDRO-1H-3-BENZAZEPIN-7-YL)OXY)-3-PYRIDINYL)-

Systematic Name

English

GSK239512

Code

English

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Code System

Code

Type

Description

SMS_ID

100000178152

PRIMARY

ChEMBL

CHEMBL3092650

PRIMARY

CAS

720691-69-0

PRIMARY

CLINICAL_TRIALS.GOV

GSK-239512

PRIMARY

This is a randomized, parallel group, placebo-controlled study designed to assess whether GSK239512 can enhance lesion remyelination in subjects with Relapsing Remitting Multiple Sclerosis (RRMS).

DRUG BANK

DB15120

PRIMARY

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Related Record

Type

Details


					4I7U5C459M

GSK-239512

ACTIVE MOIETY

Comments:

Identifies correct structure of GSK-239512.


					4I7U5C459M

GSK-239512

ACTIVE MOIETY

Comments:

Class: Anti-dementia, Antipsychotic; Mechanism of Action: Histamine H3 receptor antagonist; Highest Development Phases: Phase II for Multiple sclerosis, No development reported for Alzheimer's disease, Discontinued for Schizophrenia; Most Recent Events: 29 Jun 2015 No recent reports on development identified - Phase-II for Alzheimer's disease in Russia, South Korea, Chile, European Union (PO), 29 Jun 2015 No recent reports on development identified - Phase-I for Alzheimer's disease in Australia (PO), 29 Jun 2015 Discontinued - Phase-II for Schizophrenia in USA (PO)


					4I7U5C459M

GSK-239512

ACTIVE MOIETY

Comments:

METHODS: The study was conducted in two parts. Part A was a single-blind, placebo run-in, flexible dose titration over 9 days in two cohorts, each consisting of two patients. Part B was a double-blind, randomised, placebo controlled, parallel group, which investigated 3 flexible dose titration regimens over 4 weeks in 3 cohorts, each consisting of eight patients. RESULTS: Overall, the 5/10/20/40 .MU.g and 10/20/40/80 .MU.g regimens were well-tolerated. The regimen of 10/40/80/150 .MU.g showed the poorest tolerability likely due to the higher starting dose. There were no clinically significant abnormalities in haematology, clinical chemistry, urinalysis parameters and cardiovascular parameters. GSK239512 had positive effects on tasks of attention and memory with effect sizes between 0.56 and 1.37.


					4I7U5C459M

GSK-239512

ACTIVE MOIETY

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