(S)-(+)-2-[4-(3-Fluorobenzyloxy)benzylamino]propanamice methansulfonate
SAFINAMIDE:(S)-(+)-2-[4-(3-FLUOROBENZYLOXY)BENZYLAMINO]PROPANAMIDE METHANSULFONATE
CAS: 133865-89-1
Molecular Formula: C17H19FN2O2
(S)-(+)-2-[4-(3-Fluorobenzyloxy)benzylamino]propanamice methansulfonate - Names and Identifiers
| Name | SAFINAMIDE:(S)-(+)-2-[4-(3-FLUOROBENZYLOXY)BENZYLAMINO]PROPANAMIDE METHANSULFONATE |
| Synonyms | CS-484 FCE-26743 FCE 26743 EMD1195686 Safinamide EMD 1195686 EMD-1195686 SafinamideIntermediate 2 Safinamide ,Safinamide base N~2~-{4-[(3-fluorobenzyl)oxy]benzyl}-L-alaninamide (S)-(+)-2-[4-(3-Fluorobenzyloxy)benzylamino]propanamice methansulfonate |
| CAS | 133865-89-1 |
| EINECS | 603-772-2 |
| InChI | InChI=1/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 |
(S)-(+)-2-[4-(3-Fluorobenzyloxy)benzylamino]propanamice methansulfonate - Physico-chemical Properties
| Molecular Formula | C17H19FN2O2 |
| Molar Mass | 302.34 |
| Density | 1.189±0.06 g/cm3(Predicted) |
| Melting Point | 208-212° |
| Boling Point | 476.7±40.0 °C(Predicted) |
| Flash Point | 242.1°C |
| Solubility | DMSO |
| Vapor Presure | 2.98E-09mmHg at 25°C |
| Appearance | White to Brown Powder |
| Color | White |
| Merck | 14,8315 |
| pKa | 16.03±0.50(Predicted) |
| Storage Condition | under inert gas (nitrogen or Argon) at 2–8 °C |
| Stability | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months. |
| Sensitive | Sensitive to heat |
| Refractive Index | 1.569 |
| MDL | MFCD00897036 |
(S)-(+)-2-[4-(3-Fluorobenzyloxy)benzylamino]propanamice methansulfonate - Risk and Safety
| RTECS | TX1457385 |
(S)-(+)-2-[4-(3-Fluorobenzyloxy)benzylamino]propanamice methansulfonate - Introduction
Safinamide (EMD 1195686; FCE 26743) is a reversible MAO-B inhibitor with IC50 of 98 nM, which is 5918 times higher than that of MAO-A.
Last Update：2022-10-16 17:13:28
(S)-(+)-2-[4-(3-Fluorobenzyloxy)benzylamino]propanamice methansulfonate - Reference Information
| Overview | Safenamide (safinamide), the chemical name is (S)-2-[4-(3-fluorobenzyloxy) benzylamine] Propionamide A Sulfonate is an anti-Parkinson's disease drug developed by Netron Pharmaceutical Company, currently in phase III clinical study stage. Clinically, it has been shown that this drug can improve the motor and cognitive functions of patients with Parkinson's disease, prevent patients from having current movement disorders, and has good tolerance. |
| Parkinson's disease new drug | Safenamide (trade name: Xadago) is a new type of monoamine oxidase B(MAO-B) selective inhibitor, By blocking the voltage-dependent sodium ion channels on neurons, and then regulating the release of glutamate. This drug is recommended in combination with levodopa or other Parkinson's drugs for the treatment of advanced idiopathic Parkinson's disease. Safenamide is a highly selective and reversible third-generation type B monoamine oxidase inhibitor (selegilan is the first generation, rasagilan is the second generation), which can increase the intracellular and extracellular dopamine in the striatum Level. Unlike the already marketed stilgilam and rasagline, Safenamide also has the effect of inhibiting the release of the neurotransmitter glutamate. It is said that Safenamide is a "new drug", but in fact it is not so "new". In 2015, Europe has approved Safenamide for the treatment of advanced Parkinson's disease; On March 21, 2017, the US FDA approved Safenamide as an additional therapeutic drug for the treatment of Parkinson's patients who are taking levodopa/carbidopa and have "OFF" status. as we all know, levodopa is currently the most effective and widely used drug for the treatment of Parkinson's disease, and the proportion of patients taking drugs is as high as 75%. However, with the development of the disease, the ON-Time of levodopa will gradually shorten, resulting in the so-called "wearing-off" phenomenon. At this time, we need to combine levodopa with other drugs with different mechanisms of action. As a new selective MAO-B inhibitor, Safenamide can effectively reduce the degradation of secreted dopamine and help maintain the concentration of dopamine in the brain. In addition, Safenamide can also block voltage-dependent sodium channels on neurons, thereby inhibiting the release of glutamate. Therefore, Safenamide is a new Parkinson's disease treatment drug with both dopaminergic and non-dopaminergic mechanisms. |
| Preparation method | 1. Solid phase synthesis: Rink amide resin is hydrolyzed to remove carboxyl groups, and (S)-2-(fluorenomethoxyamido) propionic acid undergo ammonolysis reaction, remove amino protection group, then it is condensed with 4-(triisopropylsiloxy) benzaldehyde, and is reduced by sodium triacetylborohydride, then remove the phenolic hydroxyl protecting group and then form an ether with 3-fluorobenzyl alcohol, and finally take off the product from the resin to obtain this drug. This route involves multiple protection and deprotection. The route is long and the reagents used are expensive, which is not suitable for industrial production. 2. It is prepared by the reaction of (S)-2-aminopropionamide (4) and 4-(3-fluorobenzyl) benzaldehyde (6). The total yield is about 45%. Although the route is short, the raw materials used are not easy to obtain. 3. the second method is improved: the synthesis route is as follows: the specific steps are: using L-alanine (2) as raw material to prepare (S)-2-aminopropionate methyl ester hydrochloride (3), then ammonolysis to obtain 4, adding catalyst potassium iodide, replacing acetone with anhydrous ethanol as solvent, and extending the reaction time to 6 h, after extraction with toluene and recrystallization with toluene-n-hexane (1: 1), pure product 6 was prepared. The yield was increased from 78% to 91%. When preparing 1, the literature [2] condensed 4 and 6 to prepare (S)-2-[4-(3-fluorobenzyloxy) benzyimine] propionamide (7), which was then reduced with sodium cyanoborohydride, and then purified by column chromatography to obtain (S)-2-[4-(3-fluorobenzyloxy) benzylamine] propionamide (8), finally, it is salt with methanesulfonic acid to obtain 1, and the yield is 45% (calculated as 6). This method will produce the highly toxic sodium cyanide, and column chromatography purification is not suitable for large-scale production. In this study, Pd/C catalytic hydrogenation reduction was used. The product was recrystallized with toluene and then salted with methanesulfonic acid. The operation was simplified and more suitable for industrial production. The yield could be improved to 83.3%. The total yield of the improved process is 75.8%. |
| mechanism of action | this product has a variety of mechanisms of action, which can not only inhibit monoamine oxidase B(MAO-B) with high selectivity and reversibility, it can also inhibit dopamine reuptake, block voltage-dependent sodium channels, regulate calcium channels, and thus inhibit the release of valley amino acid. This product has high bioavailability of the central nervous system. Clinically, it has been shown that this drug can improve the motor and cognitive functions of patients with Parkinson's disease, prevent the patients from dyskinesia, and has good tolerance. |
| application | can be used for the treatment of Parkinson's disease. |
| Adverse reactions | Safenamide is a selective monoamine oxidase (MAO)B inhibitor. The most common adverse reactions of patients taking Safenamide include uncontrolled involuntary movement, falls, nausea and insomnia. According to the FDA, serious but uncommon risks include worsening hypertension; serotonin syndrome when used with MAO inhibitors, antidepressants or opioids; falling asleep in activities of daily living; hallucinations and psychotic behaviors; Impulse control disorders/compulsive behavior; hyperthermia and confusion after drug withdrawal; and retinopathy. |
| precautions | FDA reminds that Safenamide should not be used in patients with severe liver dysfunction. In addition, patients taking dextromethorphan, MAO inhibitors, opioids, St. John's wort, and certain antidepressants (such as serotonin-norepinephrine reuptake inhibitors, tricyclic, tetracyclic and triazolopyridine) Or patients with cyclobenzaprine should also not take Safenamide because it may cause life-threatening serotonin syndrome. |
| references | [1] xing ruijuan, Lu Tao, Liu leina, et al. synthesis of Safenamide [J]. china journal of pharmaceutical industry, 2012, 43(3):161-163. [2] Pevarello P, Bonsignori A, Dostert P, et al. Synthesis and anticonvulsant activity of a new class of 2-[(arylalky)-amino] alkanamide derivatives [J]. J Med Chem, 1998, 41(4): 579-590. |
Last Update：2024-04-09 15:16:47
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