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Safinamide

PubChem CID
131682
Structure
Safinamide_small.png
Safinamide_3D_Structure.png
Safinamide__Crystal_Structure.png
Molecular Formula
Synonyms
  • Safinamide
  • 133865-89-1
  • (S)-2-((4-((3-Fluorobenzyl)oxy)benzyl)amino)propanamide
  • Xadago
  • (2S)-2-[[4-[(3-Fluorophenyl)methoxy]phenyl]methylamino]propanamide
Molecular Weight
302.34 g/mol
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Dates
  • Create:
    2005-08-08
  • Modify:
    2025-01-11
Description
Safinamide is an amino acid amide.
Safinamide is for the treatment of parkinson's disease. It was approved in Europe in February 2015, and in the United States on March 21, 2017.
Safinamide is a Monoamine Oxidase Type B Inhibitor. The mechanism of action of safinamide is as a Monoamine Oxidase-B Inhibitor, and Breast Cancer Resistance Protein Inhibitor.
See also: Safinamide Mesylate (active moiety of).

1 Structures

1.1 2D Structure

Chemical Structure Depiction
Safinamide.png

1.2 3D Conformer

1.3 Crystal Structures

1 of 4
View All
CCDC Number
Crystal Structure Data
Crystal Structure Depiction
Crystal Structure Depiction

2 Names and Identifiers

2.1 Computed Descriptors

2.1.1 IUPAC Name

(2S)-2-[[4-[(3-fluorophenyl)methoxy]phenyl]methylamino]propanamide
Computed by Lexichem TK 2.7.0 (PubChem release 2021.10.14)

2.1.2 InChI

InChI=1S/C17H19FN2O2/c1-12(17(19)21)20-10-13-5-7-16(8-6-13)22-11-14-3-2-4-15(18)9-14/h2-9,12,20H,10-11H2,1H3,(H2,19,21)/t12-/m0/s1
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.3 InChIKey

NEMGRZFTLSKBAP-LBPRGKRZSA-N
Computed by InChI 1.0.6 (PubChem release 2021.10.14)

2.1.4 SMILES

C[C@@H](C(=O)N)NCC1=CC=C(C=C1)OCC2=CC(=CC=C2)F
Computed by OEChem 2.3.0 (PubChem release 2024.12.12)

2.2 Molecular Formula

C17H19FN2O2
Computed by PubChem 2.2 (PubChem release 2021.10.14)

2.3 Other Identifiers

2.3.1 CAS

2.3.2 European Community (EC) Number

2.3.3 UNII

2.3.4 ChEBI ID

2.3.5 ChEMBL ID

2.3.6 DrugBank ID

2.3.7 DSSTox Substance ID

2.3.8 KEGG ID

2.3.9 Metabolomics Workbench ID

2.3.10 NCI Thesaurus Code

2.3.11 Nikkaji Number

2.3.12 Pharos Ligand ID

2.3.13 RXCUI

2.3.14 Wikidata

2.3.15 Wikipedia

2.4 Synonyms

2.4.1 MeSH Entry Terms

  • (S)-2-((4-(3-fluorobenzoxy)benzyl)amino)propanamide
  • 2-(4-(3-fluorobenzyloxy)benzylamino)propionamide
  • fbap methanesulfonate
  • FCE 26743
  • FCE 28073
  • FCE-26743
  • FCE-28073
  • NW-1015
  • PNU 151774E
  • PNU-151774E
  • safinamide
  • safinamide methanesulfonate
  • Xadago

2.4.2 Depositor-Supplied Synonyms

3 Chemical and Physical Properties

3.1 Computed Properties

Property Name
Molecular Weight
Property Value
302.34 g/mol
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
XLogP3-AA
Property Value
2.2
Reference
Computed by XLogP3 3.0 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Donor Count
Property Value
2
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Hydrogen Bond Acceptor Count
Property Value
4
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Rotatable Bond Count
Property Value
7
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Exact Mass
Property Value
302.14305602 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Monoisotopic Mass
Property Value
302.14305602 Da
Reference
Computed by PubChem 2.2 (PubChem release 2021.10.14)
Property Name
Topological Polar Surface Area
Property Value
64.4 Ų
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Heavy Atom Count
Property Value
22
Reference
Computed by PubChem
Property Name
Formal Charge
Property Value
0
Reference
Computed by PubChem
Property Name
Complexity
Property Value
346
Reference
Computed by Cactvs 3.4.8.18 (PubChem release 2021.10.14)
Property Name
Isotope Atom Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Atom Stereocenter Count
Property Value
1
Reference
Computed by PubChem
Property Name
Undefined Atom Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Defined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Undefined Bond Stereocenter Count
Property Value
0
Reference
Computed by PubChem
Property Name
Covalently-Bonded Unit Count
Property Value
1
Reference
Computed by PubChem
Property Name
Compound Is Canonicalized
Property Value
Yes
Reference
Computed by PubChem (release 2021.10.14)

3.2 Chemical Classes

3.2.1 Drugs

Pharmaceuticals -> Nervous system -> Anti-parkinson drugs
S92 | FLUOROPHARMA | List of ~340 ATC classified fluoro-pharmaceuticals | DOI:10.5281/zenodo.5979646
Pharmaceuticals -> Listed in ZINC15
S55 | ZINC15PHARMA | Pharmaceuticals from ZINC15 | DOI:10.5281/zenodo.3247749
3.2.1.1 Human Drugs
Breastfeeding; Lactation; Antiparkinson Agents; Monoamine Oxidase Inhibitors;
Human drug -> Prescription
Human drug -> None (Tentative Approval); Active ingredient (SAFINAMIDE)
Human drugs -> Anti-Parkinson drugs -> Human pharmacotherapeutic group -> EMA Drug Category

5 Chemical Vendors

6 Drug and Medication Information

6.1 Drug Indication

Safinamide is indicated as an add-on treatment to levodopa with or without other medicines for Parkinson’s disease
Xadago is indicated for the treatment of adult patients with idiopathic Parkinson's disease (PD) as add-on therapy to a stable dose of Levodopa (L-dopa) alone or in combination with other PD medicinal products in mid-to late-stage fluctuating patients.

6.2 LiverTox Summary

Safinamide is an inhibitor of monoamine oxidase used as adjunctive therapy in combination with levodopa and carbidopa in the management of Parkinson’s disease. Safinamide has been associated with a low rate of serum enzyme elevations during treatment, but has not been linked to instances of clinically apparent acute liver injury.

6.3 Drug Classes

Breastfeeding; Lactation; Antiparkinson Agents; Monoamine Oxidase Inhibitors;
Antiparkinson Agents

6.4 FDA Approved Drugs

6.5 Clinical Trials

6.5.1 ClinicalTrials.gov

6.5.2 EU Clinical Trials Register

6.5.3 NIPH Clinical Trials Search of Japan

6.6 EMA Drug Information

Medicine
Category
Human drugs
Therapeutic area
Parkinson Disease
INN/Common name
safinamide
Pharmacotherapeutic Classes
Anti-Parkinson drugs
Status
This medicine is authorized for use in the European Union
Company
Zambon SpA
Market Date
2015-02-23

7 Pharmacology and Biochemistry

7.1 FDA Pharmacological Classification

FDA UNII
90ENL74SIG
Active Moiety
SAFINAMIDE
Pharmacological Classes
Established Pharmacologic Class [EPC] - Monoamine Oxidase Type B Inhibitor
Pharmacological Classes
Mechanisms of Action [MoA] - Monoamine Oxidase-B Inhibitors
Pharmacological Classes
Mechanisms of Action [MoA] - Breast Cancer Resistance Protein Inhibitors
FDA Pharmacology Summary
Safinamide is a Monoamine Oxidase Type B Inhibitor. The mechanism of action of safinamide is as a Monoamine Oxidase-B Inhibitor, and Breast Cancer Resistance Protein Inhibitor.

7.2 ATC Code

N04B
S76 | LUXPHARMA | Pharmaceuticals Marketed in Luxembourg | Pharmaceuticals marketed in Luxembourg, as published by d'Gesondheetskeess (CNS, la caisse nationale de sante, www.cns.lu), mapped by name to structures using CompTox by R. Singh et al. (in prep.). List downloaded from https://cns.public.lu/en/legislations/textes-coordonnes/liste-med-comm.html. Dataset DOI:10.5281/zenodo.4587355

N - Nervous system

N04 - Anti-parkinson drugs

N04B - Dopaminergic agents

N04BD - Monoamine oxidase b inhibitors

N04BD03 - Safinamide

7.3 Absorption, Distribution and Excretion

Absorption
Rapid with peak plasma concentrations ranging from 2 to 4 h, total bioavailability is 95%. Food prolonged the rate and did not affect the extent of absorption of safinamide.
Route of Elimination
76% renal, 1.5% faeces
Volume of Distribution
1.8 litres/kg
Clearance
total oral clearance of plasma , which accounts for parent safinamide as well as metabolites, was on average only 17.53 ± 2.71 ml/h × kg

7.4 Metabolism / Metabolites

The principal step is mediated by amidases which have not been identified, and produces safinamide acid. It is also metabolized to O-debenzylated safinamide and N-delkylated amine. The N-dealkylated amine is then oxidized to a carboxylic acid and finally glucuronidated. Dealkylation reactions are mediated by cytochrome P450s (CYPs), especially CYP3A4. Safinamide acid binds to organic anion transporter 3 (OAT3), but no clinical relevance of this interaction has been determined. Safinamide also binds to ABCG2 transiently. No other transporter affinities have been found in preliminary studies.

7.5 Biological Half-Life

22 h

7.6 Mechanism of Action

Safinamide is a unique molecule with multiple mechanisms of action and a very high therapeutic index. It combines potent, selective, and reversible inhibition of MAO-B with blockade of voltage-dependent Na+ and Ca2+ channels and inhibition of glutamate release. Safinamide has neuroprotective and neurorescuing effects in MPTP-treated mice, in the rat kainic acid, and in the gerbil ischemia model.

8 Use and Manufacturing

8.1 Uses

8.1.1 Use Classification

Human drugs -> Anti-Parkinson drugs -> Human pharmacotherapeutic group -> EMA Drug Category

9 Safety and Hazards

9.1 Hazards Identification

9.1.1 GHS Classification

Pictogram(s)
Corrosive
Acute Toxic
Environmental Hazard
Signal
Danger
GHS Hazard Statements

H301 (90.5%): Toxic if swallowed [Danger Acute toxicity, oral]

H318 (90.5%): Causes serious eye damage [Danger Serious eye damage/eye irritation]

H400 (90.5%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]

Precautionary Statement Codes

P264, P264+P265, P270, P273, P280, P301+P316, P305+P354+P338, P317, P321, P330, P391, P405, and P501

(The corresponding statement to each P-code can be found at the GHS Classification page.)

ECHA C&L Notifications Summary

Aggregated GHS information provided per 42 reports by companies from 3 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.

9.1.2 Hazard Classes and Categories

Acute Tox. 3 (90.5%)

Eye Dam. 1 (90.5%)

Aquatic Acute 1 (90.5%)

9.2 Regulatory Information

REACH Registered Substance

10 Toxicity

10.1 Toxicological Information

10.1.1 Hepatotoxicity

Safinamide has been reported to cause serum enzyme elevations in a small proportion of patients treated long term, although the abnormalities were usually mild and self-limiting and were usually no more frequent than with placebo or comparator agents. Safinamide has not been implicated in cases of acute liver injury, but such instances have been reported with nonspecific MAO inhibitors.

Likelihood score: E (unlikely cause of clinically apparent liver injury).

10.1.2 Effects During Pregnancy and Lactation

◉ Summary of Use during Lactation

No information is available on the use of safinamide during breastfeeding. Because of liver toxicity in nursing rat pups, the manufacturer recommends that the drug not be used in nursing mothers. Alternate agents are preferred.

◉ Effects in Breastfed Infants

Relevant published information was not found as of the revision date.

◉ Effects on Lactation and Breastmilk

Relevant published information was not found as of the revision date.

10.1.3 Protein Binding

88–90%

11 Associated Disorders and Diseases

12 Literature

12.1 Consolidated References

12.2 NLM Curated PubMed Citations

12.3 Springer Nature References

12.4 Thieme References

12.5 Chemical Co-Occurrences in Literature

12.6 Chemical-Gene Co-Occurrences in Literature

12.7 Chemical-Disease Co-Occurrences in Literature

13 Patents

13.1 Depositor-Supplied Patent Identifiers

13.2 WIPO PATENTSCOPE

13.3 Chemical Co-Occurrences in Patents

13.4 Chemical-Disease Co-Occurrences in Patents

13.5 Chemical-Gene Co-Occurrences in Patents

14 Interactions and Pathways

14.1 Protein Bound 3D Structures

14.2 Chemical-Target Interactions

14.3 Drug-Drug Interactions

14.4 Drug-Food Interactions

  • Avoid excessive or chronic alcohol consumption. Ingesting alcohol may increase the sedative effects of safinamide.
  • Avoid St. John's Wort. This herb may increase the risk of serotonin syndrome, and therefore, concomitant use is contraindicated.
  • Avoid tyramine-containing foods and supplements. Avoid foods containing high amounts of tyramine (>150mg) as these foods may cause a significant elevation in blood pressure. Tyramine-containing foods include cheese, red wine, fava beans, pickled food, cured food, and alcoholic beverages.
  • Take at the same time every day.
  • Take with or without food.

15 Biological Test Results

15.1 BioAssay Results

16 Classification

16.1 MeSH Tree

16.2 NCI Thesaurus Tree

16.3 ChEBI Ontology

16.4 KEGG: ATC

16.5 KEGG: Target-based Classification of Drugs

16.6 KEGG: Drug Groups

16.7 WHO ATC Classification System

16.8 FDA Pharm Classes

16.9 ChemIDplus

16.10 IUPHAR / BPS Guide to PHARMACOLOGY Target Classification

16.11 ChEMBL Target Tree

16.12 UN GHS Classification

16.13 NORMAN Suspect List Exchange Classification

16.14 EPA DSSTox Classification

16.15 PFAS and Fluorinated Organic Compounds in PubChem

16.16 MolGenie Organic Chemistry Ontology

17 Information Sources

  1. BindingDB
    LICENSE
    All data curated by BindingDB staff are provided under the Creative Commons Attribution 3.0 License (https://creativecommons.org/licenses/by/3.0/us/).
    https://www.bindingdb.org/rwd/bind/info.jsp
    (2S)-2-[({4-[(3-fluorophenyl)methoxy]phenyl}methyl)amino]propanamide
    https://www.bindingdb.org/rwd/bind/chemsearch/marvin/MolStructure.jsp?monomerid=19187
  2. ChEMBL
    LICENSE
    Access to the web interface of ChEMBL is made under the EBI's Terms of Use (http://www.ebi.ac.uk/Information/termsofuse.html). The ChEMBL data is made available on a Creative Commons Attribution-Share Alike 3.0 Unported License (http://creativecommons.org/licenses/by-sa/3.0/).
    http://www.ebi.ac.uk/Information/termsofuse.html
  3. Drug Gene Interaction database (DGIdb)
    LICENSE
    The data used in DGIdb is all open access and where possible made available as raw data dumps in the downloads section.
    http://www.dgidb.org/downloads
  4. DrugBank
    LICENSE
    Creative Common's Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/legalcode)
    https://www.drugbank.ca/legal/terms_of_use
  5. IUPHAR/BPS Guide to PHARMACOLOGY
    LICENSE
    The Guide to PHARMACOLOGY database is licensed under the Open Data Commons Open Database License (ODbL) https://opendatacommons.org/licenses/odbl/. Its contents are licensed under a Creative Commons Attribution-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-sa/4.0/)
    https://www.guidetopharmacology.org/about.jsp#license
    Guide to Pharmacology Target Classification
    https://www.guidetopharmacology.org/targets.jsp
  6. Therapeutic Target Database (TTD)
  7. CAS Common Chemistry
    LICENSE
    The data from CAS Common Chemistry is provided under a CC-BY-NC 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc/4.0/
  8. ChemIDplus
    ChemIDplus Chemical Information Classification
    https://pubchem.ncbi.nlm.nih.gov/source/ChemIDplus
  9. EPA DSSTox
    CompTox Chemicals Dashboard Chemical Lists
    https://comptox.epa.gov/dashboard/chemical-lists/
  10. European Chemicals Agency (ECHA)
    LICENSE
    Use of the information, documents and data from the ECHA website is subject to the terms and conditions of this Legal Notice, and subject to other binding limitations provided for under applicable law, the information, documents and data made available on the ECHA website may be reproduced, distributed and/or used, totally or in part, for non-commercial purposes provided that ECHA is acknowledged as the source: "Source: European Chemicals Agency, http://echa.europa.eu/". Such acknowledgement must be included in each copy of the material. ECHA permits and encourages organisations and individuals to create links to the ECHA website under the following cumulative conditions: Links can only be made to webpages that provide a link to the Legal Notice page.
    https://echa.europa.eu/web/guest/legal-notice
    Propanamide, 2-(((4-((3-fluorophenyl)methoxy)phenyl)methyl)amino)-, (S)-
    https://chem.echa.europa.eu/100.120.167
    Propanamide, 2-(((4-((3-fluorophenyl)methoxy)phenyl)methyl)amino)-, (S)- (EC: 603-772-2)
    https://echa.europa.eu/information-on-chemicals/cl-inventory-database/-/discli/details/69365
  11. FDA Global Substance Registration System (GSRS)
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  12. ChEBI
  13. FDA Pharm Classes
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  14. LiverTox
  15. Open Targets
    LICENSE
    Datasets generated by the Open Targets Platform are freely available for download.
    https://platform-docs.opentargets.org/licence
  16. ClinicalTrials.gov
    LICENSE
    The ClinicalTrials.gov data carry an international copyright outside the United States and its Territories or Possessions. Some ClinicalTrials.gov data may be subject to the copyright of third parties; you should consult these entities for any additional terms of use.
    https://clinicaltrials.gov/ct2/about-site/terms-conditions#Use
  17. Crystallography Open Database (COD)
    LICENSE
    All data in the COD and the database itself are dedicated to the public domain and licensed under the CC0 License. Users of the data should acknowledge the original authors of the structural data.
    https://creativecommons.org/publicdomain/zero/1.0/
  18. The Cambridge Structural Database
  19. European Medicines Agency (EMA)
    LICENSE
    Information on the European Medicines Agency's (EMA) website is subject to a disclaimer and copyright and limited reproduction notices.
    https://www.ema.europa.eu/en/about-us/legal-notice
  20. Drugs and Lactation Database (LactMed)
  21. Drugs@FDA
    LICENSE
    Unless otherwise noted, the contents of the FDA website (www.fda.gov), both text and graphics, are not copyrighted. They are in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from FDA. Credit to the U.S. Food and Drug Administration as the source is appreciated but not required.
    https://www.fda.gov/about-fda/about-website/website-policies#linking
  22. EU Clinical Trials Register
  23. NORMAN Suspect List Exchange
    LICENSE
    Data: CC-BY 4.0; Code (hosted by ECI, LCSB): Artistic-2.0
    https://creativecommons.org/licenses/by/4.0/
    Safinamide
    NORMAN Suspect List Exchange Classification
    https://www.norman-network.com/nds/SLE/
  24. WHO Anatomical Therapeutic Chemical (ATC) Classification
    LICENSE
    Use of all or parts of the material requires reference to the WHO Collaborating Centre for Drug Statistics Methodology. Copying and distribution for commercial purposes is not allowed. Changing or manipulating the material is not allowed.
    https://www.whocc.no/copyright_disclaimer/
  25. Japan Chemical Substance Dictionary (Nikkaji)
  26. KEGG
    LICENSE
    Academic users may freely use the KEGG website. Non-academic use of KEGG generally requires a commercial license
    https://www.kegg.jp/kegg/legal.html
    Anatomical Therapeutic Chemical (ATC) classification
    http://www.genome.jp/kegg-bin/get_htext?br08303.keg
    Target-based classification of drugs
    http://www.genome.jp/kegg-bin/get_htext?br08310.keg
  27. Metabolomics Workbench
  28. NCI Thesaurus (NCIt)
    LICENSE
    Unless otherwise indicated, all text within NCI products is free of copyright and may be reused without our permission. Credit the National Cancer Institute as the source.
    https://www.cancer.gov/policies/copyright-reuse
  29. NIPH Clinical Trials Search of Japan
  30. NLM RxNorm Terminology
    LICENSE
    The RxNorm Terminology is created by the National Library of Medicine (NLM) and is in the public domain and may be republished, reprinted and otherwise used freely by anyone without the need to obtain permission from NLM. Credit to the U.S. National Library of Medicine as the source is appreciated but not required. The full RxNorm dataset requires a free license.
    https://www.nlm.nih.gov/research/umls/rxnorm/docs/termsofservice.html
  31. Pharos
    LICENSE
    Data accessed from Pharos and TCRD is publicly available from the primary sources listed above. Please respect their individual licenses regarding proper use and redistribution.
    https://pharos.nih.gov/about
  32. Springer Nature
  33. Thieme Chemistry
    LICENSE
    The Thieme Chemistry contribution within PubChem is provided under a CC-BY-NC-ND 4.0 license, unless otherwise stated.
    https://creativecommons.org/licenses/by-nc-nd/4.0/
  34. Wikidata
  35. Wikipedia
  36. PubChem
  37. Medical Subject Headings (MeSH)
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    https://www.nlm.nih.gov/copyright.html
  38. GHS Classification (UNECE)
  39. MolGenie
    MolGenie Organic Chemistry Ontology
    https://github.com/MolGenie/ontology/
  40. PATENTSCOPE (WIPO)
CONTENTS