161735-79-1 Usage
Description
Rasagiline mesylate, also known as (R)-N-(prop-2-ynyl)-2,3-dihydro-1H-inden-1-amine methanesulfonate (Azilect), is a potent and selective irreversible monoamine oxidase B (MAO-B) inhibitor. It belongs to the propargylamine family and is a white to off-white powder, soluble in water or ethanol, and slightly soluble in isopropanol. Rasagiline mesylate is rapidly absorbed and undergoes complete biotransformation before excretion, mainly via N-dealkylation and hydroxylation, yielding three major metabolites. Both oxidative pathways are catalyzed by cytochrome P450 (CYP) enzymes, primarily the 1A2 isozyme. Rasagiline and its metabolites undergo glucuronide conjugation with subsequent urinary excretion. As a selective and irreversible inhibitor of MAO-B, its duration of action is independent of the drug's half-life and is instead determined by the regeneration rate of MAO-B.
Uses
Used in Parkinson's Disease Treatment:
Rasagiline mesylate is used as an antiparkinsonian agent for the treatment of idiopathic Parkinson's disease. It acts as a selective irreversible MAO-B inhibitor, which helps in managing the symptoms and progression of the disease.
Used in Alzheimer's Type Dementia Treatment:
Rasagiline is currently in phase II clinical trials at Teva and Eisai for the treatment of Alzheimer's type dementia. Its potential use in this application is due to its MAO-B inhibiting properties, which may help in addressing the cognitive decline associated with dementia.
Used in Monoamine Oxidase B Inhibition:
Rasagiline mesylate is used as a potent and selective irreversible MAO-B inhibitor, which is beneficial in various applications where the inhibition of this enzyme is required. Its prolonged effect may be advantageous in limiting the fluctuating responses characteristic of long-term drug treatments.
Indications
Rasagiline mesylate is a novel, potent, second-generation, selective, irreversible MAO-B inhibitor that blocks the breakdown of dopamine. It is approved for the treatment of PD. Indications for use of once-daily rasagiline are as a monotherapy in early PD and as an adjunct to levodopa in moderate to advanced disease. Rasagiline significantly improves symptoms during initial monotherapy in patients with early PD and as an adjunct treatment to levodopa in moderate-to-advanced patients. Rasagiline is well tolerated up to doses as high as 20 mg/day. Evidence for neuroprotective effect of rasagiline is as follows (Jain 2010c):
Structure activity studies have shown that the neuroprotective activity is associated with the propargyl moiety of rasagiline, which protects mitochondrial viability.
Experimental evidence supports rasagiline's neuroprotective efficacy, showing that neuronal survival is related to the anti-apoptotic properties of its propargyl moiety.
Aminoindan metabolite of rasagiline has been shown to have neuroprotective properties (Bar-Am et al. 2010).
Biochem/physiol Actions
Rasagiline mesylate is an irreversible inhibitor of monoamine oxidase selective for MAO type B over type A by a factor of fourteen. It has anti-apoptotic and neuroprotectant activity and has been used as a treatment for Parkinson′s disease.
Synthesis
1-Indanone (122) was condensed with benzyl amine to give corresponding enamine which was reduced
with sodium borohydride in ethanol to give racemic Nbenzyl-
1-inda-namine (123) in 82% yield. The racemic
benzylamine 123 was resolved with L-tartaric acid and recrystallized
from boiling water to give optical pure Rbenzylamine
124 as a tartarate salt. The recovered S-isomer
125 can be racemized under basic condition to give back as
the starting racemic 123. Compound 124 was hydrogenated
and basified to give free amine 126 in 72 % yield which was
alkylated with propargyl chloride and K2CO3 in hot acetonitrile
to yield free resagiline. Finally resagiline mesilate
(XVII) was obtained by treating resagiline with methanesulfonic
acid in refluxing IPA.
References
1) Youdim?et al.?(2001),?Rasagiline [N-propargyl-1R(+)-aminoindan], a selective and potent inhibitor of mitochondrial monoamine oxidase B; Br. J. Pharmacol.,?132?500
2) Cereda?et al.?(2017),?Efficacy of rasagiline and selegiline in Parkinson’s disease: a head-to-head 3-year retrospective case-control study; J. Neurol.,?264?1254
3) Cronin and Grealy (2017),?Neuroprotective and Neuro-restorative Effects of Minocycline and Rasagiline in Zebrafish 6-Hydroxydopamine Model of Parkinson’s Disease; Neuroscience,?367?34
4) Kang?et al.?(2017),?TrkB neurotrophic activities are blocked by α-synuclein, triggering dopaminergic cell death in Parkinson’s disease; Proc. Natl. Acad. Sci. USA,?114?10773
5) Ledreux?et al.?(2016),?BDNF levels are increased by aminoindan and rasagiline in a double lesion model of Parkinson’s disease; Brain Res.,?1631?34
Check Digit Verification of cas no
The CAS Registry Mumber 161735-79-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,6,1,7,3 and 5 respectively; the second part has 2 digits, 7 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 161735-79:
(8*1)+(7*6)+(6*1)+(5*7)+(4*3)+(3*5)+(2*7)+(1*9)=141
141 % 10 = 1
So 161735-79-1 is a valid CAS Registry Number.
InChI:InChI=1/C12H13N.CH4O3S/c1-2-9-13-12-8-7-10-5-3-4-6-11(10)12;1-5(2,3)4/h1,3-6,12-13H,7-9H2;1H3,(H,2,3,4)/t12-;/m1./s1
161735-79-1Relevant articles and documents
Improved preparation method of rasagiline racemic intermediate
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Paragraph 0049; 0050; 0055; 0056, (2020/02/29)
The invention discloses an improved preparation method of a rasagiline racemic intermediate, belongs to the technical field of medicinal chemistry, and particularly relates to an improved method for preparing an N-(2-propargyl)-2,3-dihydro-1H-indene-1-amine racemic body. According to the invention, the N-(2-propargyl)-2,3-dihydro-1H-indene-1-amine racemic body is prepared by using 1-indanone and propargylamine as raw materials through a one-pot method in the presence of a dehydrating agent; and the method is simple to operate, high in yield and good in purity, and establishes a good foundationfor subsequent preparation of rasagiline mesylate.
PROCESS FOR THE PREPARATION OF ENATIOMERICALLY PURE 1-AMINOINDAN
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, (2015/06/03)
The present invention relates to a process for the preparation of optically pure ( R) -1-aminoindan by a diastereomeric resolution of 1-aminoindan using N-acetyl-L-glutamic acid as a resolving agent. In another aspect, the invention relates to diastereomeric salts of (R) -1-aminoindan with N-acetyl-L-glutamic acid, and their use in the process for the preparation of rasagiline.
A novel synthesis of rasagiline via a chemoenzymatic dynamic kinetic resolution
Ma, Guozhen,Xu, Zhongqi,Zhang, Pengfei,Liu, Jinpo,Hao, Xilin,Ouyang, Jingping,Liang, Ping,You, Song,Jia, Xian
, p. 1169 - 1174 (2014/12/10)
A novel synthetic route for preparing rasagiline mesylate is presented using a dynamic kinetic resolution (DKR) as the key step, catalyzed by Candida antarctica lipase B (CALB) and a Pd nanocatalyst. The chiral intermediate (R)-2,3-dihydro-1-indanamine was obtained through the DKR of the racemic aminoindan rac-1 in high yield (>90%) and excellent enantioselectivity (>99% ee). The process could be conducted on a 73 g scale at 200 g/L. Rasagiline mesylate was synthesized in 25% overall yield and excellent enantioselectivity (99.9% ee) over 7 steps.