pitolisant   Click here for help

GtoPdb Ligand ID: 8924

Synonyms: BF2.649 | Ozawade® | tiprolisant [USAN] | Wakix®
Approved drug
pitolisant is an approved drug (EMA (2016), FDA (2019))
Compound class: Synthetic organic
Comment: Pitolisant is a selective antagonist/inverse agonist of the histamine H3 receptor [7-8,11].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Click here for structure editor
Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 2
Hydrogen bond donors 0
Rotatable bonds 8
Topological polar surface area 12.47
Molecular weight 295.17
XLogP 3.94
No. Lipinski's rules broken 0
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES Clc1ccc(cc1)CCCOCCCN1CCCCC1
Isomeric SMILES Clc1ccc(cc1)CCCOCCCN1CCCCC1
InChI InChI=1S/C17H26ClNO/c18-17-9-7-16(8-10-17)6-4-14-20-15-5-13-19-11-2-1-3-12-19/h7-10H,1-6,11-15H2
InChI Key NNACHAUCXXVJSP-UHFFFAOYSA-N
References
1. Celanire S, Wijtmans M, Talaga P, Leurs R, de Esch IJ. (2005)
Keynote review: histamine H3 receptor antagonists reach out for the clinic.
Drug Discov Today, 10 (23-24): 1613-27. [PMID:16376822]
2. Kollb-Sielecka M, Demolis P, Emmerich J, Markey G, Salmonson T, Haas M. (2017)
The European Medicines Agency review of pitolisant for treatment of narcolepsy: summary of the scientific assessment by the Committee for Medicinal Products for Human Use.
Sleep Med, 33: 125-129. [PMID:28449891]
3. Ligneau X, Landais L, Perrin D, Piriou J, Uguen M, Denis E, Robert P, Parmentier R, Anaclet C, Lin JS et al.. (2007)
Brain histamine and schizophrenia: potential therapeutic applications of H3-receptor inverse agonists studied with BF2.649.
Biochem Pharmacol, 73 (8): 1215-24. [PMID:17343831]
4. Ligneau X, Perrin D, Landais L, Camelin JC, Calmels TP, Berrebi-Bertrand I, Lecomte JM, Parmentier R, Anaclet C, Lin JS et al.. (2007)
BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology.
J Pharmacol Exp Ther, 320 (1): 365-75. [PMID:17005916]
5. Lin JS, Dauvilliers Y, Arnulf I, Bastuji H, Anaclet C, Parmentier R, Kocher L, Yanagisawa M, Lehert P, Ligneau X et al.. (2008)
An inverse agonist of the histamine H(3) receptor improves wakefulness in narcolepsy: studies in orexin-/- mice and patients.
Neurobiol Dis, 30 (1): 74-83. [PMID:18295497]
6. Panula P, Chazot PL, Cowart M, Gutzmer R, Leurs R, Liu WL, Stark H, Thurmond RL, Haas HL. (2015)
International Union of Basic and Clinical Pharmacology. XCVIII. Histamine Receptors.
Pharmacol Rev, 67 (3): 601-55. [PMID:26084539]
7. Pierson PD, Fettes A, Freichel C, Gatti-McArthur S, Hertel C, Huwyler J, Mohr P, Nakagawa T, Nettekoven M, Plancher JM et al.. (2009)
5-hydroxyindole-2-carboxylic acid amides: novel histamine-3 receptor inverse agonists for the treatment of obesity.
J Med Chem, 52 (13): 3855-68. [PMID:19456097]
8. Schwartz JC. (2011)
The histamine H3 receptor: from discovery to clinical trials with pitolisant.
Br J Pharmacol, 163 (4): 713-21. [PMID:21615387]
9. Stocking EM, Letavic MA. (2008)
Histamine H3 antagonists as wake-promoting and pro-cognitive agents.
Curr Top Med Chem, 8 (11): 988-1002. [PMID:18673168]
10. Szakacs Z, Dauvilliers Y, Mikhaylov V, Poverennova I, Krylov S, Jankovic S, Sonka K, Lehert P, Lecomte I, Lecomte JM et al.. (2017)
Safety and efficacy of pitolisant on cataplexy in patients with narcolepsy: a randomised, double-blind, placebo-controlled trial.
Lancet Neurol, 16 (3): 200-207. [PMID:28129985]
11. Łazewska D, Kuder K, Ligneau X, Camelin JC, Schunack W, Stark H, Kieć-Kononowicz K. (2009)
Diether derivatives of homo- or substituted piperidines as non-imidazole histamine H3 receptor ligands.
Bioorg Med Chem, 17 (8): 3037-42. [PMID:19329325]