 Home > Encyclopedia > Safinamide

Safinamide

Safinamide structure

CAS No:
133865-89-1
Formula:
C17H19FN2O2
Chemical Name:
Safinamide
Synonyms:
Propanamide,2-[[[4-[(3-fluorophenyl)methoxy]phenyl]methyl]amino]-,(2S)-;Propanamide,2-[[[4-[(3-fluorophenyl)methoxy]phenyl]methyl]amino]-,(S)-;(2S)-2-[[[4-[(3-Fluorophenyl)methoxy]phenyl]methyl]amino]propanamide;FCE 26743;Safinamide;(S)-2-[[4-[(3-Fluorobenzyl)oxy]benzyl]amino]propanamide;EMD 1195686;(2S)-2-[[4-[(3-Fluorophenyl)methoxy]phenyl]methylamino]propanamide;(S)-2-[[[4-[(3-Fluorophenyl)methoxy]phenyl]methyl]amino]propanamide
Categories:
Biochemical Engineering > Inhibitors

Description

Safinamide (EMD 1195686; FCE 26743) selectively and reversibly inhibits MAO-B with IC50 of 98 nM, exhibits 5918-fold selectivity against MAO-A.IC50 value: 98 nM [1]Target: MAO-BSafinamide (EMD 1195686; FCE 26743; ) is a highly selective and reversible monoamine oxidase type B (MAO-B) inhibitor that increases neostriatal dopamine concentration. In addition, Safinamide (EMD 1195686; FCE 26743; ) is voltage-dependent sodium and calcium channel blocker. Safinamide (EMD 1195686; FCE 26743; )

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.|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.

Safinamide Basic Attributes

Molecular Weight：

302.347

Exact Mass：

302.34

EC Number：

603-772-2

UNII：

90ENL74SIG

ATC Code：

N04B|N04BD03|N - Nervous system

Characteristics

PSA：

64.4

XLogP3：

2.2

Density：

1.189±0.06 g/cm3(Predicted)

Melting Point：

208-212°

Boiling Point：

476.7±40.0 °C(Predicted)

Flash Point：

242.1±27.3 °C

Refractive Index：

1.570

Vapor Pressure：

2.98E-09mmHg at 25°C

Safety Information

RTECS Number：

TX1457385

Precautionary statement(s)：

P201, P202, P264, P270, P273, P280, P281, P301+P310, P301+P312, P305+P351+P338, P308+P313, P310, P321, P330, P337+P313, P391, P405, P501

Hazard Statements：

H301

GHS Classification：

|Danger|H301 (92.68%): Toxic if swallowed [Danger Acute toxicity, oral]|P264, P270, P273, P280, P301+P310, P305+P351+P338, P310, P321, P330, P391, P405, and P501|Aggregated GHS information provided by 41 companies from 2 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Toxicity

Toxicity Summary：

uncontrolled involuntary movement, falls, nausea, and trouble sleeping or falling asleep (insomnia) Patients who have an overdose may experience hypertension (high blood pressure), orthostatic hypotension, hallucinations, psychomotor agitation, nausea, vomiting, and dyskinesia.

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.

Protein Binding：

88–90%

Drug Information

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.

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.

Drug Classes：

Antiparkinson Agents

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.|76% renal, 1.5% faeces|1.8 litres/kg|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

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.

Biological Half-Life：

22 h

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.

MeSH Entry Terms：

(S)-2-((4-(3-fluorobenzoxy)benzyl)amino)propanamide

Safinamide Use and Manufacturing

Uses

Safinamide may exert its in vivo effects through different mechanisms of action. It did not display activity against >80 different types of dopamine, glutamate, adenosine, serotonin, muscarinic, nicotinic, and GABA receptors. Conversely, potent modulation of DA metabolism, blockade of Na+/Ca2+ channels, and inhibition of glutamate release have been demonstrated. It has pointed out that the electrophysiological and neurochemical effects of safinamide are apparent at effective anticonvulsant conc

Use Classification：

Human drugs -> Xadago -> EMA Drug Category|Anti-Parkinson drugs -> Human pharmacotherapeutic group|Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients

Computed Properties

Molecular Weight:302.34
XLogP3:2.2
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:7
Exact Mass:302.14305602
Monoisotopic Mass:302.14305602
Topological Polar Surface Area:64.4
Heavy Atom Count:22
Complexity:346
Defined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes

Recommended Suppliers of Safinamide

HANGZHOU LEAP CHEM CO., LTD. Contact Supplier

CN
5 YRS

Business licensed

Trader Supplier of Intermediates,Building blocks,API,Silicones,Peptides,Lab chemicals,Biochemicals,Pharmaceuticals,Screening Compounds,Food Additives

Safinamide

CAS No.: 133865-89-1

Content: 99.00%

Inquiry
Shandong Airuike Chemical Co., Ltd. Contact Supplier

CN
2 YRS

Business licensed

Trader Supplier of api,Intermediates,Organic Chemistry,Inorganic Chemistry,Daily Chemicals,Cosmetic Raw Materals,CATALYST AND AUXILIARY,FLAVORS AND FRAGRANCES,Chemical Pesticides,ADDITIVE

Safinamide CAS133865-89-1 factory price

CAS No.: 133865-89-1

Grade: Analytical Reagent

Content: 99%

Inquiry
Henan Lihao Chem Plant Limited Contact Supplier

CN
5 YRS

Business licensed

Trader Supplier of PVC resin,pvc paste resin,melamine

Safinamide 99% see COA kanbei

CAS No.: 133865-89-1

Grade: Industrial Grade

Content: 99%

Inquiry
Alicorn Pharmaceutical Contact Supplier

CN
4 YRS

Business licensed Certified factory

Manufactory Supplier of Betahistine Mesylate,Azilsartan Medoxomil Potassium,Pimavanserin Tartrate,Iguratimod

Safinamide api

CAS No.: 133865-89-1

Grade: Pharmaceutical Grade

Content: 99%

Inquiry
Zison Pharmaceutical (Shandong)Co.,Ltd. Contact Supplier

CN
4 YRS

Business licensed Certified factory

Manufactory Supplier of Avatrombopag,Lenvatinib,Safinamide mesylate,Axitinib

Safinamide 133965-89-1

CAS No.: 133865-89-1

Grade: Pharmaceutical Grade

Content: 99%

Inquiry