99755-59-6 Usage
Description
Rotigotine, also known as Neupro, is a non-ergot dopamine agonist drug that is used for the treatment of Parkinson's disease. It is a nonergoline that is available as a silicone-based, self-adhesive matrix, transdermal system for continuous delivery over a 24-hour period. Rotigotine is a non-selective dopamine receptor agonist with high affinity for D1, D2, and D3 receptors and lesser affinity for D4 and D5 receptor subtypes.
Uses
Used in Parkinson's Disease Treatment:
ROTIGOTINE is used as a dopamine agonist for the treatment of Parkinson's disease. It helps to alleviate symptoms such as tremors, muscle stiffness, and bradykinesia by providing continuous dopaminergic stimulation, which is associated with a lower incidence of dyskinesias.
Used in Early-Stage Parkinson's Disease:
ROTIGOTINE is used as a selective dopamine agonist for monotherapy in early-stage Parkinson's disease. It 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.
Used in Transdermal Patch Form:
ROTIGOTINE is used as a transdermal patch for continuous delivery over a 24-hour period. This allows for a steady release of the drug and avoids the low bioavailability associated with oral administration.
Used in Dopamine Receptor Agonist Research:
ROTIGOTINE is used as a non-selective dopamine receptor agonist in research studies, providing insights into the binding profiles and anti-Parkinsonian effects of various dopamine agonists.
Used in Brand Name Neupro:
ROTIGOTINE is used under the brand name Neupro, which was approved in May 2007 for the treatment of early-stage Parkinson's disease.
Originator
Aderis (US)
Clinical Use
Treatment of Parkinson’s disease
Restless legs syndrome (RLS)
Synthesis
The synthesis described by the originators at Discovery
Therapeutics Inc. (now known as Aderis Pharmaceuticals)
is shown in the scheme. The synthesis utilizes the
chiral methoxy tetralin 62 as starting precursor which was
obtained via chiral crystallization procedure described in a
patent literature [34]. Demethylation of tetraline 62 with
refluxing 40% HBr solution for several hours provided phenol
63 in 96% yield. Reaction of the amine 63 with 2-
thiophenylethyl tosylate 64 in refluxing xylene for 24-32 h in
the presence of 0.6 equiv sodium carbonate gave the desired
rotigotine (IX) without requiring chromatographic purification.
The ratio of sodium carbonate to the amine was critical
to achieving good yields (59-84% yield) without requiring
extensive purification. Rotigotine was isolated as the HCl
salt.
Drug interactions
Potentially hazardous interactions with other drugs
Antipsychotics: avoid concomitant use (antagonism
of effect).
Metoclopramide: avoid concomitant use (antagonism
of effect).
Metabolism
Rotigotine is metabolised in the gut wall and liver
by N-dealkylation as well as direct and secondary
conjugation. Main metabolites are sulfates and
glucuronide conjugates of the parent compound as well as
N-desalkyl-metabolites, which are biologically inactive.
Approximately 71% of the rotigotine dose is excreted
in urine and a smaller part of about 23% is excreted in
faeces.
Check Digit Verification of cas no
The CAS Registry Mumber 99755-59-6 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 9,9,7,5 and 5 respectively; the second part has 2 digits, 5 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 99755-59:
(7*9)+(6*9)+(5*7)+(4*5)+(3*5)+(2*5)+(1*9)=206
206 % 10 = 6
So 99755-59-6 is a valid CAS Registry Number.
InChI:InChI=1/C19H25NOS/c1-2-11-20(12-10-17-6-4-13-22-17)16-8-9-18-15(14-16)5-3-7-19(18)21/h3-7,13,16,21H,2,8-12,14H2,1H3/t16-/m0/s1
99755-59-6Relevant articles and documents
Synthesis of Pharmaceutically Relevant 2-Aminotetralin and 3-Aminochroman Derivatives via Enzymatic Reductive Amination
Citoler, Joan,Harawa, Vanessa,Marshall, James R.,Bevinakatti, Han,Finnigan, James D.,Charnock, Simon J.,Turner, Nicholas J.
supporting information, p. 24456 - 24460 (2021/10/19)
2-Aminotetralin and 3-aminochroman derivatives are key structural motifs present in a wide range of pharmaceutically important molecules. Herein, we report an effective biocatalytic approach towards these molecules through the enantioselective reductive coupling of 2-tetralones and 3-chromanones with a diverse range of primary amine partners. Metagenomic imine reductases (IREDs) were employed as the biocatalysts, obtaining high yields and enantiocomplementary selectivity for >15 examples at preparative scale, including the precursors to Ebalzotan, Robalzotan, Alnespirone and 5-OH-DPAT. We also present a convergent chemo-enzymatic total synthesis of the Parkinson's disease therapy Rotigotine in 63 % overall yield and 92 % ee.
Novel Process for Preparation of Rotigotine and Intermediates Thereof
-
, (2019/08/26)
The present invention relates to a novel process for the preparation of Rotigotine of formula (I) and intermediates thereof.
Enantioselective Synthesis of β-Aminotetralins via Chiral Phosphoric Acid-catalyzed Reductive Amination of β-Tetralones
Park, Do Young,Kim, Kyung-Hee,Cheon, Cheol-Hong
supporting information, p. 462 - 467 (2017/12/07)
A new protocol for the synthesis of chiral β-aminotetralins has been developed via chiral phosphoric acid-catalyzed asymmetric reductive amination of β-tetralones using a Hantzsch ester as an organic hydride donor. Various chiral β-aminotetralins were obtained in good yields with good to high enantioselectivities. Furthermore, the utility of our new protocol was successfully demonstrated in the enantioselective synthesis of rotigotine. (Figure presented.).
