XALIPRODEN

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H22F3N
Molecular Weight	381.4334
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

FC(F)(F)C1=CC=CC(=C1)C2=CCN(CCC3=CC=C4C=CC=CC4=C3)CC2

InChI

InChIKey=WJJYZXPHLSLMGE-UHFFFAOYSA-N

InChI=1S/C24H22F3N/c25-24(26,27)23-7-3-6-22(17-23)20-11-14-28(15-12-20)13-10-18-8-9-19-4-1-2-5-21(19)16-18/h1-9,11,16-17H,10,12-15H2

HIDE SMILES / InChI

Molecular Formula	C24H22F3N
Molecular Weight	381.4334
Charge	0
Count

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

Description
Sources: http://www.alzforum.org/therapeutics/xaliproden | http://adisinsight.springer.com/drugs/800001601 | https://www.ncbi.nlm.nih.gov/pubmed/19616185 | https://www.ncbi.nlm.nih.gov/pubmed/19814656

Xaliproden is an orally active 5HT1-A receptor antagonist that was being developed by Sanofi. It has been evaluated for the treatment of Alzheimer's disease and amyotrophic lateral sclerosis (ALS), and protection against peripheral neurotoxicity associated with certain cancer chemotherapies. Two large, 18-month, clinical trials of xaliproden (monotherapy or adjunctive therapy, respectively) in patients with mild to moderate AD (MMSE, 16–26, inclusive) were completed in 2007. Failure to demonstrate sufficient efficacy in both trials resulted in cancelation of the xaliproden development program for AD in September 2007.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Serotonin 1a (5-HT1a) receptor 172 Target ID: CHEMBL273 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19814656 \| https://www.ncbi.nlm.nih.gov/pubmed/8314196	Agonist 2678		4.3 nM [IC50]
Serotonin 1a (5-HT1a) receptor 172 Target ID: CHEMBL214 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19508400	Agonist 2678		9.0 null [pKi]

Conditions

Condition	Modality	Highest Phase	Product
Alzheimer’s disease 272 Sources: http://www.alzforum.org/therapeutics/xaliproden https://clinicaltrials.gov/ct2/show/NCT00103649	Primary	Phase III 656	Unknown Approved Use Unknown
Amyotrophic lateral sclerosis 41 Sources: http://www.alzforum.org/therapeutics/xaliproden http://adisinsight.springer.com/drugs/800001601 https://www.ncbi.nlm.nih.gov/pubmed/19814656	Primary	Phase III 656	Unknown Approved Use Unknown
Cancer pain 10 Sources: http://adisinsight.springer.com/drugs/800001601	Palliative	Phase III 656	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
Efficacy and safety of xaliproden in amyotrophic lateral sclerosis: results of two phase III trials.	2004 Jun	15204012
Xaliproden in amyotrophic lateral sclerosis: early clinical trials.	2004 Jun	15204011
Quantification of neurotrophin mRNA expression in PMN mouse: modulation by xaliproden.	2004 May-Aug	15171816
Xaliproden (SR57746A) induces 5-HT1A receptor-mediated MAP kinase activation in PC12 cells.	2005 Apr-Jun	15888246
MAPK activation via 5-hydroxytryptamine 1A receptor is involved in the neuroprotective effects of xaliproden.	2005 Jan-Mar	15698508
Pharmacological strategies for the prevention of Alzheimer's disease.	2006 Jan	16370917
Peripheral neuropathy related to chemotherapy.	2007 Aug	17693343
Small molecule activators of the Trk receptors for neuroprotection.	2008 Dec 3	19090982
Chemotherapy-induced peripheral neuropathy: prevention and treatment strategies.	2008 Jul	18571399
Current and emerging treatments for amyotrophic lateral sclerosis.	2009	19966906
Towards a quantitative representation of the cell signaling mechanisms of hallucinogens: measurement and mathematical modeling of 5-HT1A and 5-HT2A receptor-mediated ERK1/2 activation.	2009	18762202
Role of oxaliplatin in the treatment of colorectal cancer.	2009 Feb	19436599
Amyotrophic lateral sclerosis.	2009 Feb 3	19192301
Drug development for Alzheimer's disease: where are we now and where are we headed?	2009 Jun	19616185
Defining survival as an outcome measure in amyotrophic lateral sclerosis.	2009 Jun	19506136
SR 57746A/xaliproden, a non-peptide neurotrophic compound: prospects and constraints for the treatment of nervous system diseases.	2009 Nov	19814656
5-HT1A receptors are involved in the effects of xaliproden on G-protein activation, neurotransmitter release and nociception.	2009 Sep	19508400

Patents

Sample Use Guides

In Vivo Use Guide

Patients with clinically probable or definite ALS of more than 6 months and less than 5 years duration were randomly assigned to placebo, 1 mg or 2 mg xaliproden orally once daily as monotherapy in Study 1

Route of Administration: Oral

In Vitro Use Guide

Xaliproden (1 uM) increases the phenotypic survival of embryonic purified mouse motoneurons in vitro to the same extent as brain-derived neurotrophic factor (100 ng/ml), and increases the outgrowth and number of their neurites. It acts in a dose-dependent manner up to 1 uM which is the optimal concentration. Above this concentration, its neurotrophic effect decreases.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:17:30 GMT 2023` Edited by `admin` on `Fri Dec 15 16:17:30 GMT 2023`
Record UNII	V8QL94KNQO
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

XALIPRODEN

Official Name

English

XALIPRODEN [USAN]

Common Name

English

PYRIDINE, 1,2,3,6-TETRAHYDRO-1-(2-(2-NAPHTHALENYL)ETHYL)-4-(3-(TRIFLUOROMETHYL)PHENYL)-

Systematic Name

English

SR-57746

Code

English

XALIPRODEN [MI]

Common Name

English

Xaliproden [WHO-DD]

Common Name

English

xaliproden [INN]

Common Name

English

SR57746

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C1509