Rasagiline

Base Information

• Chemical Name: Rasagiline
• CAS No.: 136236-51-6
• Molecular Formula: C12H13N
• Molecular Weight: 171.242
• Hs Code.: 2921499090
• European Community (EC) Number: 851-611-1
• NSC Number: 759639
• UNII: 003N66TS6T
• DSSTox Substance ID: DTXSID3041112
• Nikkaji Number: J573.894F
• Wikipedia: Rasagiline
• Wikidata: Q420685
• NCI Thesaurus Code: C66510
• RXCUI: 134748
• Pharos Ligand ID: L2PY466DVAZJ
• Metabolomics Workbench ID: 43523
• ChEMBL ID: CHEMBL887
• Mol file: 136236-51-6.mol

Synonyms:2,3-dihydro-N-2-propynyl-1H-inden-1-amine-(1R)-hydrochloride;AGN 1135;AGN-1135;Azilect;N-2-propynyl-1-indanamine;N-propargyl-1-aminoindan mesylate;rasagiline;rasagiline hydrochloride;TVP 101;TVP 1022;TVP-101;TVP-1022;TVP1022

Chemical Property of Rasagiline

Chemical Property:

• Melting Point: 148 °C
• Refractive Index: 1.606
• Boiling Point: 305.5 °C at 760 mmHg
• PKA: 6.95±0.20(Predicted)
• Flash Point: 146.8 °C
• PSA: 12.03000
• Density: 1.05 g/cm³
• LogP: 2.28760
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility.: Dichloromethane
• XLogP3: 1.8
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 2
• Exact Mass: 171.104799419
• Heavy Atom Count: 13
• Complexity: 212

Purity/Quality:

98%,99%, ^*data from raw suppliers

Rasagiline ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiparkinson Agents
• Canonical SMILES: C#CCNC1CCC2=CC=CC=C12
• Isomeric SMILES: C#CCN[C@@H]1CCC2=CC=CC=C12
• Recent ClinicalTrials: A Phase 3 Study With P2B001 in Subjects With Early Parkinson's
• Recent EU Clinical Trials: A Phase 3, Twelve-week, Multi-Center, Multinational, Randomized, Double-Blind, Double-Dummy, Parallel Group Study to Determine the Efficacy, Safety and Tolerability of P2B001 Once Daily Compared to its Individual Components in Subjects With Early Parkinson’s Disease and to a Calibration Arm of Pramipexole ER.
• Recent NIPH Clinical Trials: Rasagiline Tablets Special Drug Use-Results Survey 'Survey on Long-term Safety'
• Description: Rasagiline is a second-generation, irreversible monoamine oxidase type B (MAO-B) inhibitor that has been launched for the treatment of Parkinson’s disease (PD). Unlike its predecessor selegiline, it is not metabolized to amphetamine derivatives and is, therefore, devoid of the sympathomimetic activity responsible for adverse side effects. Rasagiline is, however, similar to selegiline in the retention of the propargylamine moiety; this essential pharmacophore binds covalently to selectively form an irreversible bond with the flavin adenine dinucleotide portion of the MAO-B enzyme. As an adjunct therapy, rasagiline treats the fluctuations in motor symptoms. The R-enantiomer exhibits 4-times the potency of the S-enantiomer, so the synthetic method begins with the optical resolution of racemic N-benzyl-1-aminoindan using (R,R)-tartaric acid as the resolving agent. Once isolated, the enantiomerically-enriched salt is submitted to hydrogenolysis to afford 1(R)- aminoindane that is subsequently propargylated to provide rasagiline. It is formulated as its mesylate salt, and the recommended dosage of rasagiline is 1 mg/day, with or without levodopa. Entacapone, a catecholamine- O-methyltransferase inhibitor known as an effective add-on therapy for motor fluctuations, was used as a comparator. Rasagiline reduced the time spent in the “off” state while increasing the “on” time.
• Uses: 5HT4 receptor agonist, peristaltic stimulant. Rasagiline, is a selective and irreversible propargylamine inhibitor of monoamine oxidase which has been used to increase the availability of dopamine at striatal receptors as a method to treat Parkinson’s disease.
• Indications: Rasagiline has a role in the treatment of PD by virtue of its proven ability to reduce the signs of PD in both the “on” and “off” states, and to improve global function. It appears to be of value in early stages of PD as well as after the appearance of clinical fluctuations in response to LD. Rasagiline also has a promising but not fully explored potential to halt or slow down the progression of PD, as well as other clinical conditions. The accumulating evidence of rasagiline’s neuroprotective effects in animal and cellular models is both intriguing and exciting. Further careful scientific basic and clinical studies and clinical experience are needed to establish the full therapeutic benefits of rasagiline for the treatment of PD.
• Clinical Use: Rasagiline [R(+)-N-propargyl-1-aminoindan] mesylate (Azilect?) was approved by the FDAin May of 2006 as monotherapy in early disease and as an adjunct to levodopa in more advanced disease. The recommended doses are 1 mg once a day in early disease and an initial dose of 0.5 mg once a day in advanced disease that can be increased to 1 mg once a day if needed. It produces selective irreversible MAO-B inhibition. Platelet MAO-B inhibition is dose-dependent; one hour after ingestion, platelet MAOB inhibition is 35% with 1 mg rasagiline and 99% with 10 mg rasagiline. By day 6, rasagiline 2 mg/day inhibits over 99% of platelet MAO-B. After discontinuing rasagiline, it takes approximately two weeks for MAO-B activity to return to baseline values. The area under the curve (AUC) and maximum concentration (Cmax) increase linearly with rasagiline dosage. The plasma half-lives of rasagiline and its active metabolite 1(R)-aminoindan are 3.5 hours and 11 hours, respectively. As rasagiline irreversibly inhibits MAO-B, the serum (pharmacokinetic) half-life does not correlate with its functional (pharmacodynamic) half-life. Rasagiline up to 20 mg/day was well tolerated in healthy male volunteers. Dry mouth, headache, nausea, thirst, and abdominal discomfort were the most common adverse effects but tended to be mild. There were no significant effects on vital signs, lab values, physical exam, or EKG.
• Drug interactions: Potentially hazardous interactions with other drugs Analgesics: avoid with dextromethorphan; avoid with pethidine (risk of serious adverse reactions) - allow at least 14 days before starting pethidine. Antidepressants: avoid with other MAOIs (can lead to hypertensive crisis) - allow at least 14 days before starting a MAOI; avoid with fluoxetine and fluvoxamine; allow 5 weeks between stopping fluoxetine and starting rasagiline; allow 14 days between stopping rasagiline and starting fluoxetine or fluvoxamine; increased CNS toxicity with SSRIs, tricyclics and vortioxetine. Sympathomimetics: concomitant use is not recommended.

Technology Process of Rasagiline

There total 47 articles about Rasagiline 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%

(R-(+)-N-propargyl-1-aminoindan)L-tartarate → rasagiline (136236-51-6,185517-74-2)

Guidance literature:

With sodium hydroxide; In water; toluene; at 45 ℃; for 0.25h; pH=13 - 14;

Reference yield: 95.0%

(R)-tert-butyl 2,3-dihydro-1H-inden-1-yl(prop-2-ynyl)carbamate (1224439-21-7) → rasagiline (136236-51-6,185517-74-2)

Guidance literature:

(R)-tert-butyl 2,3-dihydro-1H-inden-1-yl(prop-2-ynyl)carbamate; With hydrogenchloride; water; In 1,4-dioxane; at 20 ℃; for 0.5h; Inert atmosphere;

With sodium hydrogencarbonate; In 1,4-dioxane; water; Inert atmosphere;

Reference yield: 91.6%

rasagiline mesylate (161735-79-1) → rasagiline (136236-51-6,185517-74-2)

Guidance literature:

With sodium hydroxide; In water; at 3 - 5 ℃; for 1h; pH=7.5 - 11; Product distribution / selectivity;

upstream raw materials:

(R)-N-indan-1-yl-4-nitro-N-prop-2-ynyl-benzenesulfonamide

INDANE

(R)-N-indan-1-yl-4-nitrobenzenesulfonamide

Propargylamine

Downstream raw materials:

rasagiline mesylate

N-Methyl Rasagiline

R-(+)-N-propargyl-1-aminoindane salicylate

R-(+)-N-propargyl-1-aminoindane L-(+)-mandelate

Refernces

• 1、 Sun, Yongqiang,Zhang, Xinyu,Yan, Yimin,Tu, Yongrui,Feng, Xiaohui,Jiang, Wei,Zheng, Feng. "Identification and genotoxicity evaluation of two carbamate impurities in rasagiline". . p. 106268 - 106274. Retrieved 2016.
• 2、 -. "Improved method for preparing rasagiline". Paragraph 0031-0041. . Retrieved 2020/07/12.
• 3、 -. "CHIRAL CATALYST AND METHOD FOR ASYMMETRIC REDUCTION OF AN IMINE". Paragraph 00179; 00180; 00181; 00182; 00183; 00184. . Retrieved 2019/04/16.