1665-48-1

Usage

Uses

Used in Pharmaceutical Industry:
Metaxalone is used as a skeletal muscle relaxant for the treatment of painful peripheral musculoskeletal conditions and spasticity from upper motor neuron syndromes. It helps in reducing muscle spasm, limitations in normal motion, and pain associated with these conditions.
Used in Pain Management:
Metaxalone is used as an adjunct therapy in combination with analgesics to address low back pain and other musculoskeletal pain issues. Its muscle-relaxing properties complement the pain-relieving effects of analgesics, providing a more comprehensive approach to pain management.
While the provided materials do not specify other industries where Metaxalone might be used, its primary application is within the pharmaceutical industry for the treatment of musculoskeletal conditions and pain management.

Originator

Skelaxin,Robins,US,1962

Manufacturing Process

Urea (118 g, 1.96 mols) was added to 192 g (0.98 mol) of 3-(3',5'- dimethylphenoxy)-1,2-propane-diol which had previously been heated to 150°C. The reaction mixture was then heated rapidly to 195° to 200°C and maintained at this temperature for 5 hours with constant stirring. The resulting mixture was partitioned between water and ethyl acetate and the ethyl acetate layer was dried over sodium sulfate and concentrated. The residue was distilled in vacuo and the fraction boiling at 220° to 225°C/1.5 mm was collected. Yield, 172 g (79%). The distillate was crystallized from dry ethyl acetate; MP, 121.5° to 123°C.

Therapeutic Function

Muscle relaxant

InChI:InChI=1/C12H15NO3/c1-8-3-9(2)5-10(4-8)15-7-11-6-13-12(14)16-11/h3-5,11H,6-7H2,1-2H3,(H,13,14)

Upstream product

• 59365-66-1 3-(3,5-dimethyl-phenoxy)-propane-1,2-diol 
• 57-13-6 urea 
• 153756-95-7 4-acetamidophenyl N-<3-(3,5-dimethylphenoxy)-2-hydroxypropyl>carbamate 
• 66766-07-2 1-amino-3-(3,5-dimethylphenoxy)-2-propanol 
• 598-55-0 methyl carbamate 
• 2451-62-9 teroxirone 
• 108-68-9 3,5-Dimethylphenol 
• 105-67-9 2,4-Xylenol 

Downstream Products

• 1312886-76-2 Metaxalone adipic acid (1:1) 
• 1312886-78-4 Metaxalone salicylic acid (1:1) 

Related news

Original ArticleKinetics study of Metaxalone (cas 1665-48-1) degradation under hydrolytic, oxidative and thermal stress conditions using stability-indicating HPLC method10/01/2019

An isocratic stability indicating RP-HPLC–UV method is presented for the determination of metaxalone (MET) in the presence of its degradation products. The method uses Dr. Maisch C18 column (250 mm×4.6 mm, 5 μm) with mobile phase consisting of acetonitrile–potassium dihydrogen orthophosphate...detailed

Solubilities of chlormezanone, Metaxalone (cas 1665-48-1) and methocarbamol in supercritical carbon dioxide09/27/2019

The solubilities of three active pharmaceutical ingredients (APIs) in supercritical carbon dioxide were measured in this study using a semi-flow apparatus. These APIs are chlormezanone (C11H12ClNO3S), metaxalone (C12H15NO3) and methocarbamol (C11H15NO5) that are all used as skeletal muscle relax...detailed

Screening and characterization of cocrystal formation of Metaxalone (cas 1665-48-1) with short-chain dicarboxylic acids induced by solvent-assisted grinding approach09/24/2019

A solvent-assisted grinding approach was used to investigate the possible cocrystal formation between metaxalone and short-chain dicarboxylic acids (HOOC(CH2)nCOOH, n = 0–3). Differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) microspectroscopy, and powder X-ray diffracti...detailed

Short CommunicationQuantitative determination of Metaxalone (cas 1665-48-1) in human plasma by LC-MS and its application in a pharmacokinetic study09/09/2019

A simple and rapid method using liquid chromatography–mass spectrometry (LC-MS) for the determination of metaxalone in human plasma has been developed and validated. Letrozole was used as the internal standard (IS). The plasma samples were simply treated with acetonitrile which allowed the prec...detailed

Lower melting pharmaceutical cocrystals of Metaxalone (cas 1665-48-1) with carboxamide functionalities09/07/2019

Supramolecular reactions between a muscle relaxant drug, Metaxalone, 5-[(3,5-dimethylphenoxy)methyl]-2-oxazolidinone with a few carboxamides like nicotinamide, isonicotinamide, salicylamide and carboxylic acid coformers such as 3-hydroxybenzoic acid, 4-hydroxybenzoic acid resulted binary cocryst...detailed

Relevant academic research and scientific papers

Solid Phase Behavior, Polymorphism, and Crystal Structure Features of Chiral Drug Metaxalone

In addition to the previously known A-rac and B-rac polymorphs of the chiral drug metaxalone 1, an enantiopure A-(S)-form was obtained and studied. According to X-ray analysis, the crystalline organization of this form is close to the A-rac-1 polymorph. Crystallization of metaxalone melts is accompanied by the formation of a previously unknown metastable C-phase, which in the case of both racemic and enantiomeric samples are transformed into A-rac-1 or A-(S)-1. Analysis of the PXRD and IR spectra of crystalline samples revealed a similarity of the internal structure for the A-(S)-1, A-rac-1, C-(S)-1, and C-rac-1 crystalline forms and the essential difference of all of these phases from the B-rac-1 phase. According to the thermochemical data, the dependences of the change in the Gibbs free energy for all the phases studied are plotted in the interval from the melting point to 20 °C. Under standard conditions, the crystalline modifications of metaxalone, relative to δG0, form such a series: B-rac-1 A-(S)-1 ≈ A-rac-1 C-rac-1 C-(S)-1. A model that describes all the experimentally revealed features of metaxalone crystallization is proposed.

METHOD OF PREPARATION OF METAXALONE

The present invention relates to a method of preparation of metaxalone comprising reaction of triglycidyl isocyanurate (TGIC) with m-xylenol, characterized in that said reaction is carried out in a solvent mixture comprising an aprotic polar solvent with dielectric constant greater than or equal to 30 and at least one other solvent selected from the group comprising apolar solvents and aprotic polar solvents with dielectric constant below 30 said solvent mixture comprising from 5 to 40 wt. % of said first solvent and from 95 to 60 wt. % of said second solvent, adding the TGIC at a temperature between 30°C and 50°C, and after adding the TGIC, raising the temperature of the reaction solution to a value between 80°C and 180°C in a time between 120 and 180 minutes at a rate of increase not greater that 1.25°C per minute. The invention also relates to a metaxalone with a reduced content of impurities derived from incomplete reactions and/or side reactions of the method of production.

PROCESS FOR PREPARATION OF METAXALONE

An improved process for the preparation of Metaxalone of formula I wherein, reacting 3,5-dimethyl phenol with 3-chloro-1,2-propane diol in presence of a base, to produce 3-(3,5-dimethylphenoxy)propane-1,2-diol which is further reacted with urea in presence of polyalkylene glycol to obtain Metaxalone, which is optionally crystallized in ethyl acetate in presence of mineral acid.

SUBSTITUTED OXAZOLIDINONES

The present invention relates to new oxazolidinone modulators of skeletal muscle function and tone, pharmaceutical compositions thereof, and methods of use thereof.

METAXALONE SYNTHESIS

A process for preparing metaxalone comprising reacting 3-(3,5-dimethylphenoxy)-1-amino-2-propanol with methyl carbamate in the presence of a strong base to obtain metaxalone.

Metaxalone polymorphs

The invention provides two crystalline forms A and B of the skeletal muscle relaxant and anxiolytic agent, Metaxalone of formula (I), and a process for preparation thereof. The two crystalline forms A and B are bioavailable. The invention further provides pharmaceutical compositions comprising the two bioavailable crystalline forms, useful for the relief of discomforts associated with acute, painful musculoskeletal conditions.

Method for producing 5-aryloxymethyl-2-oxazolidinones

The present invention provides a method for making 5-aryloxymethyl-2-oxazolidinone and derivatives thereof having the general formula of: wherein R1and R2are hydrogen, alkyl, or alkoxyl group and wherein the alkyl or alkoxyl group contains no more than three carbon atoms in straight or branched chain. The invention involves the fusion of a triglycidyl isocyanurate (TGIC) with an unsubstituted or a mono- or di-substituted phenol.

Process for the preparation of metaxalone

A process for the preparation of 5-(3,5-dimethylphenoxymethyl)-2-oxazolidinone, which includes: a) reacting 3,5-dimethylphonel with epichlorohydrin to obtain a mixture of 1-(3,5-dimethylphenoxy)2,3-epoxy propane (1) and 1-(3,5-dimethylphenoxy)-3-chloro-2-propanol (2); b) reacting the mixture of (1) and (2) obtained from step (a) with benzylamine to obtain a first compound; c) reducing the first compound with hydrogen in presence of ammonia, to obtain a second compound; and d) reacting the second compound with dimethylcarbonate in the presence of a strong base to obtain 5-(3,5-dimethlphenoxymethyl)-2-oxazolidinone.

Cyclization-Activated Prodrugs: N-(Substituted 2-hydroxyphenyl and 2-hydroxypropyl)carbamates Based on Ring-Opened Derivatives of Active Benzoxazolones and Oxazolidinones as Mutual Prodrugs of Acetaminophen

N-(Substituted 2-hydroxyphenyl)- and N-(substituted 2-hydroxypropyl)carbamates based on masked active benzoxazolones (model A) and oxazolidinones (model B), respectively, were synthesized and evaluated as potential drug delivery systems.A series of alkyl and aryl N-(5-chloro-2-hydroxyphenyl)carbamates 1 related to model A was prepared.These are open drugs of the skeletal muscle relaxant chlorzoxazone.The corresponding 4-acetamidophenyl ester named chloracetamol is a mutual prodrug of chloroxazone and acetaminophen.Chlorzacetamol and two other mutual prodrugs of active bezoxazolones and acetaminophen were obtained in a two-step process via condensation of 4-acetamidophenyl 1,2,2,2-tetrachloroethyl carbonate with the appropiate anilines.Based on model B, two mutual prodrugs of acetaminophen and active oxazolidinones (metaxalone and mephenoxalone) were similarly obtained using the appropiate amines.All the carbamate prodrugs prepared were found to release the parent drugs in aqueous (pH 6-11) and plasma (pH 7.4) media.The detailed mechanistic study of prodrugs 1 carried out in aqueous medium at 37 deg C shows a change in the Broensted-type relationship log t1/2 vs pKa of the leaving groups ROH: log t1/2 = 0.46pKa - 3.55 for aryl and trihalogenoethyl esters and log t1/2 = 1.46pKa - 16.03 for alkyl esters.This change is consistent with a cyclization mechanism involving a change in the rate-limiting step from formation of a cyclic tetrahedral intermediate (step k1) to departure of the leaving group ROH (step k2) when the leaving group ability decreases.This mechanism occurs for all the prodrugs related to model A.Regeneration of the parent drugs from mutual prodrugs related to model B takes place by means of a rate-limiting elimination-addition reaction (E1cB mechanism).This affords acetaminophen and the corresponding 2-hydroxypropyl isocyanate intermediates which cyclize at any pH to the corresponding oxazolidinone drugs.As opposed to model A, the rates of hydrolysis of mutual prodrugs of model B clearly exhibit a catalytic role of the plasma.It is concluded from the plasma studies that the carbamate substrates can be enzymatically transformed into potent electrophiles, i.e., isocyanates.In the case of the present study, the prodrugs are 2-hydroxycarbamates for which the propinquity of the hydroxyl residue and the isocyanate group enforces a cyclization reaction.This mechanistic particularity precludes their potential toxicity in terms of potent electrophiles capable of modifying critical macromolecules.

Compositions to suppress gastric bleeding in indomethacin and phenylbutazone therapy

Methods of treating symptomatic conditions of inflammation due to chronic and acute rheumatic and degenerative joint disease with a combination of indomethacin or phenylbutazone and a phenoxymethyl-2-oxazolidinone resulting in beneficial reduction in side effects of ulceration and bleeding in the lower intestinal tract normally associated with indomethacin and phenylbutazone and compositions containing the combination are disclosed.