Rotigotine

Base Information

• Chemical Name: Rotigotine
• CAS No.: 99755-59-6
• Molecular Formula: C19H25NOS
• Molecular Weight: 315.48
• Hs Code.: 2934990002
• European Community (EC) Number: 619-458-3
• UNII: 87T4T8BO2E
• DSSTox Substance ID: DTXSID5046772
• Nikkaji Number: J285.097D
• Wikipedia: Rotigotine
• Wikidata: Q411985
• NCI Thesaurus Code: C77566
• RXCUI: 616739
• Pharos Ligand ID: ZKLCX3YBDKCX
• Metabolomics Workbench ID: 149434
• ChEMBL ID: CHEMBL1303
• Mol file: 99755-59-6.mol

Synonyms:(+)-5,6,7,8-tetrahydro-6-(propyl(2-(2-thienyl)ethyl)amino)-1-naphthol;(+--)-5,6,7,8-tetrahydro-6-(propyl(2-(2-thienyl)ethyl)amino)-1-naphthol;1-naphthalenol, 5,6,7,8-tetrahydro-6-(propyl(2-(2-thienyl)ethyl)amino)-;2-(N-n-propyl-N-2-thienylethylamino)-5-hydroxytetralin;N 0437;N 0437, (+-)-isomer;N 0437, (-)-isomer;N 0437, (R)-isomer;N 0437, hydrochloride, (R)-isomer;N 0437, hydrochloride, (S)-isomer;N 0923;N 0924;N-0437;N-0923;N-0924;Neupro;racemic N-0437;rotigotine;rotigotine (+-)-form;Rotigotine CDS;rotigotine, (+)-;rotigotine, (+--)-

Chemical Property of Rotigotine

Chemical Property:

• Vapor Pressure: 1.84E-09mmHg at 25°C
• Melting Point: 78 °C
• Refractive Index: 1.611
• Boiling Point: 470.1 °C at 760 mmHg
• PKA: 10.49±0.40(Predicted)
• Flash Point: 238.1 °C
• PSA: 51.71000
• Density: 1.15 g/cm³
• LogP: 4.26570
• Storage Temp.: room temp
• Water Solubility.: Insoluble in water
• XLogP3: 4.9
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 6
• Exact Mass: 315.16568559
• Heavy Atom Count: 22
• Complexity: 337

Purity/Quality:

≥98.0% ^*data from raw suppliers

Rotigotine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 22

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiparkinson Agents
• Canonical SMILES: CCCN(CCC1=CC=CS1)C2CCC3=C(C2)C=CC=C3O
• Isomeric SMILES: CCCN(CCC1=CC=CS1)[C@H]2CCC3=C(C2)C=CC=C3O
• Recent ClinicalTrials: The Practical Effect of Neupro
• Recent EU Clinical Trials: Comparative, randomized, open, crossover clinical trial to investigate adhesiveness of a newly developed rotigotine-containing transdermal patch in patients with Parkinson's disease
• Recent NIPH Clinical Trials: Safety and PK study of LY03003
• Description: While levodopa is still considered the cornerstone of treatment of Parkinson’s disease, many patients begin to experience treatment-related problems, such as a wearing-off phenomenon and the development of dyskinesias as the disease progresses. Continuous dopaminergic stimulation by means of a dopamine agonist has been recognized as being associated with a lower incidence of dyskinesias. Using a selective dopamine agonist as monotherapy in early disease may delay the onset of levodopa therapy, or at a minimum, lower its dose in adjunctive situations to minimize the adverse neurotoxic effects of levodopa. Rotigotine is a nonergolinic dopamine D3/D2/D1 receptor agonist, and it is the first dopamine agonist to be launched as a transdermal patch. Rotigotine is a non-selective dopamine receptor agonist with pEC50 values of 9.6, 10.4, 8.2, 7.7, and 7.7 for D1, D2, D3, D4, and D5, respectively. It demonstrates a high-affinity for D1, D2, and D3 with lesser affinity for D4 and D5 receptor subtypes. This binding profile is similar to that of apomorphine and pergolide but differentiated from that of pramipexole and ropinirole, which have a more narrow profile of receptor specificity. Each of these agonists demonstrates anti-Parkinsonian effects in animal and clinical models through their ability to directly activate dopamine receptors.
• Uses: It is a non-ergot dopamine agonist drug and is indicated for the treatment of Parkinson disease.
• Clinical Use: Treatment of Parkinson’s disease Restless legs syndrome (RLS)
• Drug interactions: Potentially hazardous interactions with other drugs Antipsychotics: avoid concomitant use (antagonism of effect). Metoclopramide: avoid concomitant use (antagonism of effect).

Technology Process of Rotigotine

There total 45 articles about Rotigotine 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: 98.0%

rotigotine hydrochloride (125572-93-2,102120-99-0,125572-92-1) → rotigotine (99755-59-6,112835-48-0)

Guidance literature:

With sodium carbonate; In dichloromethane; water;

Reference yield: 94.0%

(S)-6-(propyl(2-(thiophen-2-yl)ethyl)amino)-5,6,7,8-tetrahydronaphthalen-1-yl acetate hydrobromide (1231158-76-1) → rotigotine (99755-59-6,112835-48-0)

Guidance literature:

With water; sodium hydroxide; In methanol; at 20 ℃; for 3h; Product distribution / selectivity;

Reference yield: 93.0%

(2S)-5-methoxy-N-propyl-N-(2'-(thien-2-yl)ethyl)tetralin-2-amine (1148154-91-9) → rotigotine (99755-59-6,112835-48-0)

Guidance literature:

With hydrogen bromide; In acetic acid; for 4h; Reflux; Green chemistry;

upstream raw materials:

rotigotine hydrochloride

2-(2-thienyl)ethyl tosylate

Desthienyl-Rotigotine

Thiophene-2-acetic acid

Downstream raw materials:

rotigotine hydrochloride

(S)-6-(propyl(2-(thiophen-2-yl)ethyl)amino)-5,6,7,8-tetrahydronaphthalen-1-yl acetate hydrochloride

(S)-6-(propyl(2-thiophen-2-ylethyl)amino)-5,6,7,8-tetrahydronaphthalen-1-ol hydrogen tartrate

(S)-6-(propyl(2-thiophen-2-ylethyl)amino)-5,6,7,8-tetrahydronaphthalen-1-ol dihydrogen citrate