Safinamide

Base Information

• Chemical Name: Safinamide
• CAS No.: 133865-89-1
• Molecular Formula: C17H19FN2O2
• Molecular Weight: 302.348
• European Community (EC) Number: 603-772-2
• UNII: 90ENL74SIG
• DSSTox Substance ID: DTXSID601010282
• Nikkaji Number: J621.455J
• Wikipedia: Safinamide
• Wikidata: Q2211523
• NCI Thesaurus Code: C76771
• RXCUI: 1922448
• Pharos Ligand ID: DTWNHFHALMXH
• Metabolomics Workbench ID: 149883
• ChEMBL ID: CHEMBL396778
• Mol file: 133865-89-1.mol

Synonyms:(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

Chemical Property of Safinamide

Chemical Property:

• Vapor Pressure: 2.98E-09mmHg at 25°C
• Melting Point: 208-212°
• Refractive Index: 1.569
• Boiling Point: 476.698 °C at 760 mmHg
• PKA: 16.03±0.50(Predicted)
• Flash Point: 242.098 °C
• PSA: 64.35000
• Density: 1.19 g/cm³
• LogP: 3.45930
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility.: Soluble in DMSO (up to 50 mg/ml).
• XLogP3: 2.2
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 7
• Exact Mass: 302.14305602
• Heavy Atom Count: 22
• Complexity: 346

Purity/Quality:

98%min ^*data from raw suppliers

Safinamide >98.0%(HPLC) ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiparkinson Agents
• Canonical SMILES: CC(C(=O)N)NCC1=CC=C(C=C1)OCC2=CC(=CC=C2)F
• Isomeric SMILES: C[C@@H](C(=O)N)NCC1=CC=C(C=C1)OCC2=CC(=CC=C2)F
• Recent ClinicalTrials: Effect of Safinamide on Sleep Quality in Patients With Parkinson's Disease
• Recent EU Clinical Trials: A randomized, double-blind, placebo controlled, multicentre study to evaluate the effect of safinamide on freezing of gait (FOG) in mid- to late-stage fluctuating PD patients
• Recent NIPH Clinical Trials: ME2125 Phase II/III (ME2125-3)
• Description: Safinamide (133865-89-1) is a selective and reversible inhibitor of monoamine oxidase B (MAO-B, IC50=98 nM with greater than 100-fold selectivity over MAO-A.1?Displays anticonvulsant activity2?and protects against kainate-induced seizures and hippocampal neurodegeneration in rat models3. Reduces overactive glutamatergic signaling via use-dependent sodium channel blockade.4?A novel therapeutic for Parkinson’s disease with multiple modes of action.5?Effective as an add-on to dopamine agonist therapy in early Parkinson’s.6
• Indications: In 2003 positive preliminary results from a phase II trial of safinamide in epilepsy were announced. This open-labeled study was initiated to assess tolerability and drug–drug interaction (DDI) of safinamide in 48 patients with uncontrolled seizures that had already been treated with up to three other antiepileptic drugs. Starting with an initial oral dose of 50mg d?1, safinamide was increased every two weeks up to 300 mg d?1 or to the maximum tolerated dose. An interim analysis of the first 29 patients who completed the study showed excellent tolerability. In this group, no DDI was noted at any of the tested doses in that safinamide did not alter the kinetics of the other antiepileptic drugs. In this interim analysis safinamide was shown to be well tolerated in patients with medically intractable seizures. No serious AEs occurred in the study. Even though the study was not designed and powered to provide proof of efficacy, the sponsor reported that preliminary data showed a significant reduction in median seizure frequency from 50mg progressing up to the highest dose. In 2005 safinamide was administered to a total of 10 patients with RLS that were enrolled into a single-center, phase II open-labeled pilot study. Each patient was administered safinamide (100 mg d?1) at bedtime for 2 weeks. A significant improvement in all efficacy parameters studied was observed when patients received safinamide. RLS is a neurological disorder characterized by jerky movements of the lower extremities that appear mostly in the evening and during sleep. As reported in a press release, safinamide was also found to be well tolerated and did not exhibit any clinically relevant side effects, but no study results have been published.
• Clinical Use: Highly selective and reversible MAO-B inhibitor: Treatment of Parkinson’s disease
• Drug interactions: Potentially hazardous interactions with other drugs Analgesics: avoid with pethidine. Antibacterials: possible enhanced hypotensive effect with linezolid and tedizolid. Antidepressants: increased risk of hypertension and CNS excitation with SSRIs and tricyclics - adjust SSRI or tricyclic doses, avoid or adjust dose of fluoxetine and fluvoxamine; possible enhanced hypotensive effect with MAOIs and moclobemide - avoid. Sympathomimetics: use with caution.

Technology Process of Safinamide

There total 23 articles about Safinamide which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 96.0%

(S)-2-[4-(3-fluorobenzyloxy)benzylideneamino]propanamide (1000370-31-9) → safinamide (133865-89-1)

Guidance literature:

With potassium borohydride; In methanol;

Reference yield: 92.0%

L-alanine amide (7324-05-2) + 4-(3-fluoro-benzyloxy)-benzaldehyde (66742-57-2) → safinamide (133865-89-1)

Guidance literature:

L-alanine amide; 4-(3-fluoro-benzyloxy)-benzaldehyde; In methanol; at 20 - 25 ℃; for 1h;

With hydrogen; 5 % platinum on carbon; In methanol; at 20 - 35 ℃; for 5h; under 750.075 - 3750.38 Torr; Product distribution / selectivity;

Reference yield: 86.0%

N2-{4-[(3-fluorobenzyl)oxy]benzyl}-N2-[(2-nitrophenyl)sulfonyl]-L-alaninamide → safinamide (133865-89-1)

Guidance literature:

With potassium carbonate; thiophenol; In N,N-dimethyl-formamide; at 20 ℃;

DOI:10.1055/s-0033-1341104

upstream raw materials:

4-(3-fluoro-benzyloxy)-benzaldehyde

(S)-alaninamide hydrochloride

L-alanine amide

(S)-2-[4-(3-fluorobenzyloxy)benzylideneamino]propanamide

Downstream raw materials:

safinamide mesylate

safinamide mesylate

Refernces

• 1、 Higa, Vanessa M.,Omori, Alvaro T.. "A Two Hour Synthesis of the Anti-Parkinson Drug Safinamide Methanesulfonate". supporting information. p. 1433 - 1436. Retrieved 2021/07/20.
• 2、 -. "PROCESS FOR PREPARING SAFINAMIDE". . . Retrieved 2021/02/12.