123441-03-2 Usage
Uses
Antidepressant
Definition
ChEBI: A carbamate ester obtained by formal condensation of the carboxy group of ethyl(methyl)carbamic acid with the phenolic OH group of 3-[(1S)-1-(dimethylamino)ethyl]phenol. A reversible cholinesterase inhibitor.
Brand name
Exelon (Novartis).
General Description
Rivastigmine (Exelon, EA 713) is apseudoirreversible noncompetitive carbamate inhibitor ofAChE. Although the half-life is approximately 2 hours,the inhibitory properties of this agent last for 10 hours becauseof the slow dissociation of the drug from the enzyme.The Food and Drug Administration (FDA) approved its usein mild-to-moderate Alzheimer disease in April 2000. InJuly 2007, rivastigmine was granted approval for use inmanaging mild-to-moderate dementia associated withParkinson disease.
Pharmacokinetics
Rivastigmine is a centrally selective, arylcarbamate AChEI that was approved in 2000 for oral administration in the treatment of AD. It has an
elimination half-life of 1.4 to 1.7 hours but is able to inhibit AChE for up to 10 hours. Because of the slow dissociation of the carbamylated
enzyme, it has been referred to as a pseudo-irreversible AChEI. Like donepezil, rivastigmine exhibits a low level of hepatotoxicity. It is
rapidly and extensively hydrolyzed in the CNS by cholinesterase with minimal involvement of CYP450. The phenolic metabolite is excreted
primarily via the kidneys.
Clinical Use
Mild-moderate dementia in Alzheimer’s disease
Idiopathic Parkinson’s disease
Drug interactions
Potentially hazardous interactions with other drugs
Muscle relaxants: enhances effect of suxamethonium;
antagonises effect of non-depolarising muscle
relaxants.
Metabolism
Rivastigmine is the tertiary amines that
are rapidly absorbed from the gastrointestinal tract, as
are tacrine, donepezil, and galanthamine, whereas quaternary
ammonium compounds are poorly absorbed
after oral administration. Nevertheless, quaternary ammonium
compounds like neostigmine and pyridostigmine
are orally active if larger doses are employed.
Only the quaternary ammonium inhibitors do not readily
enter the CNS. Because of their high lipid solubility
and low molecular weight, most of the organophosphates
are absorbed by all routes of administration;
even percutaneous exposure can result in the absorption
of sufficient drug to permit the accumulation of
toxic levels of these compounds.
Check Digit Verification of cas no
The CAS Registry Mumber 123441-03-2 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,2,3,4,4 and 1 respectively; the second part has 2 digits, 0 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 123441-03:
(8*1)+(7*2)+(6*3)+(5*4)+(4*4)+(3*1)+(2*0)+(1*3)=82
82 % 10 = 2
So 123441-03-2 is a valid CAS Registry Number.
InChI:InChI=1/C14H22N2O2/c1-6-16(5)14(17)18-13-9-7-8-12(10-13)11(2)15(3)4/h7-11H,6H2,1-5H3/t11-/m0/s1
123441-03-2Relevant articles and documents
Kinetic Modeling of the Blood Oxygenation Level Dependent (BOLD) Signals and Biocatalytic Reactions Observed in the Human Brain Using MRI: An Analysis of Normal and Pathological Conditions
Bykov, Valeriy I.,Semenova, Nataliya A.,Tsybenova, Svetlana B.,Varfolomeev, Sergey D.
, (2020)
A kinetic model describing the pulse of increased oxygen concentrations and the subsequent changes in the concentration of N-acetylaspartate in the excited nervous tissue of the human brain in response to an external signal is presented. The model is based on biochemical data, a multistage and nonlinear dynamic process the BOLD signal and N-acetylaspartate. The existence of multiple steady states explains the triggering effect of the system. The inhibitory effect of the substrate is a necessary factor for the autostabilization of N-acetylaspartate. The kinetic model allows the dynamic behavior of previously unmeasurable metabolites, namely, products of the hydrolysis of N-acetylaspartate, such as acetic and aspartic acid, and glutamic acid to be predicted. Kinetic modeling of the BOLD signal and the subsequent hydrolysis of N-acetylaspartate provides information about the biochemical and dynamic characteristics of some pathological conditions (schizophrenia, Canavan disease, and the superexcitation of the neural network).
Group-assisted Purification (GAP) Chemistry/Technology in synthesizing the chiral intermediate of rivastigmine and its ?-Alkyl benzylamine analogues
Yang, Bing,Zhang, Chun-Yan,Xu, Jing,Zheng, Da-Jun,Wang, Xiao-Ying,Dai, Hong,Shi, Yu-Jun,Zhu, Hai-Liang
, p. 1065 - 1068 (2019)
Introduction of (S)-configuration is the key step in the synthesis of the anti-dementia drug Rivastigmine. Twenty-one alkylation products were obtained through simple washing with hexane/ethyl acetate (v/v: 10/1) in good yields (>85%) and high diastereoselectivity (up to >99:1 dr). Moreover, the chiral auxiliary could be easily dissociated and readily regenerated. That is, the synthesis was proved to follow group-assisted purification (GAP) chemistry/technology. In addition, the chiral amine produced by this asymmetric alkylation reaction was effectively used in the synthesis of Rivastigmine.
SYNTHESIS OF NOVEL INTERMEDIATE(S) FOR PREPARING RIVASTIGMINE
-
, (2020/04/10)
The present invention relates to novel intermediate(s), which are useful for the preparation of Rivastigmine compound of formula (I) and its pharmaceutically acceptable salts. The present invention further relates to the processes for the preparation of such novel intermediate(s) and preparation of Rivastigmine using such novel intermediate(s).
