21498-08-8 Usage
Chemical Properties
Crystalline Solid
Originator
Lofetensin,Nattermann,W. Germany,1981
Uses
Different sources of media describe the Uses of 21498-08-8 differently. You can refer to the following data:
1. a2-Adrenoceptor agonist related structurally to Clonidine. Used in treatment of opioid withdrawal symptoms; antihypertensive.
2. α2-Adrenoceptor agonist related structurally to Clonidine. Used in treatment of opioid withdrawal symptoms; antihypertensive.
3. Lofexidine hydrochloride is an α2-adrenergic receptor agonist (Kd = 7.6 nM for rat cerebral cortex membranes) that has transient antihypertensive effects. It is used in managing opioid withdrawal symptoms during detoxification from heroin and methadone.
Manufacturing Process
10.4 ml of absolute ethanol are added to 57.5g of α-2,6-
dichlorophenoxypropionitrile, followed by the introduction of 100 ml of
chloroform dried over phosphorus pentoxide; 10.4 g of carefully dried
hydrogen chloride being slowly introduced with stirring and cooling with
ice/common salt. Most of the chloroform and excess hydrogen chloride is then
removed by filtration in vacuo at room temperature, and dry ether added to
the residue until the imido acid ester hydrochloride is quantitatively
precipitated. The α-dichlorophenoxypropionimido acid ethyl ester
hydrochloride can be obtained analytically pure in the form of white, strongly
hygroscopic crystals by repeated dissolution in a little absolute ethanol in the
absence of heat, and precipitation with ether.The crude α-(2,6-dichlorophenoxy)propionamido acid ethyl ester hydrochloride
is added in portions to a stirred, ice-cooled solution of 29.5 g of anhydrous
ethylenediamine in 200 ml of absolute ethanol in such a way that the
temperature does not exceed 0°C to 5°C. The cooling bath is then removed
and the reaction mixture heated for 1 hour on a water bath to approximately
70°C.After cooling, unreacted ethylenediamine is neutralized in a cooling mixture
with the absolute ethanolic hydrochloric acid, filtered off from any components
that are insoluble in ethanol and approximately two-thirds of the solvent
filtered off under suction in a water jet pump vacuum. Residual quantities ofethylenediamine dihydrochloride are precipitated in fractions by the careful
addition of ethyl methyl ketone, after which the imidazoline hydrochloride is
separated off by the addition of dry ether. Following repeated recrystallization
from ethanol ether, 2-[α-(2,6-dichlorophenoxy)ethyl]-δ2-imidazoline
hydrochloride is obtained in the form of small white crystals melting at 221°C
to 223°C.
Brand name
Lofexidine (Rhone-Poulenc Rorer).
Therapeutic Function
Antihypertensive
Biological Activity
lofexidine is a α2-receptor agonist for opioid detoxification. lofexidine shows a strong affinity for the α2a-receptor subtype [1].the α2 adrenergic receptor is a g protein-coupled receptor (gpcr) consisting three highly homologous subtypes, α2a-, α2b-, and α2c-adrenergic. the α-receptors in brain are important presynaptic modulators of central noradrenergic function (autoreceptors) and postsynaptic mediators of many effects of catecholamines and related drugs. the α2-adrenergic agonists can be used as antihypertensives and preanesthetic agents [2].lofexidine is extensively absorbed, reaching peak concentrations at approximately 3 hours after oral administration. the mean maximum serum concentrations following a single 1.2 or 2.0 mg dose in healthy male adults were 1755 ± 306 and 2795 ± 593 ng/ml, respectively [1].
references
[1] gish e c, miller j l, honey b l, et al. lofexidine, an α2-receptor agonist for opioid detoxification[j]. annals of pharmacotherapy, 2010, 44(2): 343-351.[2] scheinin m, lomasney j w, hayden-hixson d m, et al. distribution of α2-adrenergic receptor subtype gene expression in rat brain[j]. molecular brain research, 1994, 21(1): 133-149.
Check Digit Verification of cas no
The CAS Registry Mumber 21498-08-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 2,1,4,9 and 8 respectively; the second part has 2 digits, 0 and 8 respectively.
Calculate Digit Verification of CAS Registry Number 21498-08:
(7*2)+(6*1)+(5*4)+(4*9)+(3*8)+(2*0)+(1*8)=108
108 % 10 = 8
So 21498-08-8 is a valid CAS Registry Number.
InChI:InChI=1/C11H12Cl2N2O.ClH/c1-7(11-14-5-6-15-11)16-10-8(12)3-2-4-9(10)13;/h2-4,7H,5-6H2,1H3,(H,14,15);1H
21498-08-8Relevant articles and documents
An Easy, Convenient, and Safe Process for the Synthesis of Lofexidine Hydrochloride
Donnola, Monica,Airoldi, Annalisa,Barozza, Alessandro,Roletto, Jacopo,Paissoni, Paolo
, p. 1816 - 1821 (2021)
A very efficient, cost-effective, and easily scalable process for the synthesis of lofexidine hydrochloride (1), an alpha 2-adrenergic receptor agonist used for treating opioid withdrawal is presented. Process development allows the preparation of lofexidine hydrochloride (1) through a one-pot amidation/imidazoline ring formation reaction, starting from ethyl 2-(2,6-dichlorophenoxy)propionate (13) and ethylenediamine (5) by the action of titanium isopropoxide. The required intermediate ethyl 2-(2,6-dichlorophenoxy)propionate (13) can efficiently be obtained through O-alkylation of 2,6-dichlorophenol (2) with ethyl 2-chloropropionate (12) using potassium carbonate as an acid-scavenger agent.
A PROCESS FOR THE SYNTHESIS OF LOFEXIDINE
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Page/Page column 4; 13-14, (2021/01/22)
Disclosed is a process for the synthesis of lofexidine of formula (I) and the hydrochloride salt thereof (II), from ethyl 2-(2,6-dichlorophenoxy)propionate (III) and ethylenediamine in the presence of tetravalent titanium alkoxides, preferably titanium isopropoxide, in an apolar solvent such as toluene. A further object of the present invention is a process for the preparation of the intermediate ethyl 2-(2,6-dichlorophenoxy)propionate (III) from 2,6-dichlorophenol and ethyl 2-chloropropionate in the presence of a polar aprotic solvent and an alkali or alkaline earth carbonate salt, preferably potassium carbonate. Both processes are more cost-effective and more easily industrially scalable than the known procedures, thus enabling the active ingredient to be obtained with high yields at a limited cost.
