XALIPRODEN HYDROCHLORIDE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C24H22F3N.ClH
Molecular Weight	417.894
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

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

InChI

InChIKey=WVHBEIJGAINUBW-UHFFFAOYSA-N

InChI=1S/C24H22F3N.ClH/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;1H

HIDE SMILES / InChI

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
Xaliproden: SR 57746, SR 57746A, xaliproden hydrochloride, xaliprodene.	2003	14584974
Quantification of neurotrophin mRNA expression in PMN mouse: modulation by xaliproden.	2004 May-Aug	15171816
Highlights From: the 2006 American Society of Clinical Oncology Gastrointestinal Cancers Symposium San Francisco, CA, January 2006.	2006 Mar	16635277
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
Defining survival as an outcome measure in amyotrophic lateral sclerosis.	2009 Jun	19506136

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.

Name

Type

Language

XALIPRODEN HYDROCHLORIDE

Common Name

English

XALIPRODEN HYDROCHLORIDE [JAN]

Common Name

English

SR-57746A

Common Name

English

SR 57746A

Common Name

English

XALIPRODEN HYDROCHLORIDE [MI]

Common Name

English

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

Systematic Name

English

XALIPRODEN HCL

Common Name

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/00/015