Paramethadione

The 5-methyl-5-ethyloxazolidine-2,4-dione may be prepared by reacting methyl ethyl ketone with sodium cyanide and with ammonium thiocyanate followed by desulfurization. This intermediate may also be prepared by condensing a-hydroxy-a-methylbutyramide with ethyl chlorocarbonate or by condensing ethyl a-hydroxy-a-methylbutyrate with urea. Another method described (Traube and Aschar, Ber., 46, 2077-1913) consists in the condensation of ethyl a-hydroxy-a-methylbutyrate with guanidine followed by hydrolysis. 

Chemical Abstracts Registry No. 115-67-3 Trade Name Manufacturer 

Therapeutic Function Anticonvulsant Chemical Name 5-ethyl-3,5-dimethyl-2,4-oxazolidinedione Common Name Isoethadione Structural Formula h.c,. 

About 143.1 grams (one mol) of 5-methyl-5-ethyloxazolidine-2,4-dione is dissolved in 300 cc of methanol containing 23 grams of sodium. To the above mixture is added 126 grams of dimethyl sulfate in 10 cc portions while the temperature is maintained at about 50°C by external cooling. The mixture is then heated briefly to boiling, cooled, diluted with about 500 cc of water and extracted with two 250 cc portions of benzene. The benzene extract is separated, washed once with sodium bicarbonate solution and once with water. The benzene is removed by evaporation on a steam bath and the residue is fractionally distilled. The material boiling at 112° to 116°C at 25 mm pressure is taken no = 1.4495. Upon further fractionation, a very pure specimen boils at 10r-102°C at 11 mm. 

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Treatment of 49 with a strong base such as sodium ethoxide serves to remove the last proton on the heterocyclic ring. Alkylation of the resulting carbanion with allyl bromide affords aloxidone (50) methyl sulfate on the carbanion gives trimetha-dione (51), while ethyl sulfate yields paramethadione (52). ... 

Metoclopramide HCI Metrizoic acid Paramethadione Pentapiperide methosulfate... 

C4HJO 78-93-3) see Beclobrate Bemegride Clinofibrate Clobetasone butyrate Ethionamide Ethosuximide Methylpentynol Paramethadione 1-butene... 

C2jH3 07 67212-74-2) see Alclometasone dipropionate 2 -hydroxy-4 -(3-methyl-2-butenyloxy)acetophenone (C,3H] 03 24672-83-1) see Sofalcone 2-hydroxy-2-methylbutyric acid ethyl ester (C7H14O3 77-70-3) see Paramethadione 2-hydroxy-2-methylbutyronitrile (Ci H NO 4111-08-4) see Paramethadione 5(R)-(hydroxymethyl)-2-cyclopenten-l(R)-ol (C(jH,(,02 143395-28-2) see Abacavir 2-[l-(hydroxymethyl)cyclopropyl]acctonitrile (QH9NO 152922-71-9) see Montelukast sodium ( )-cis-2-hydroxymethyl-Af,Af-diethyl-l-phenylcyclo-propanecarboxamide... 

CNNa 143-33-9) see Alclofenac Alpidem Amphetaminil Atorvastatin calcium Azatadine Calcium pantothenate Carnitine Clopidogrel hydrogensulfate Clortermine Dexrazoxane Diclofenac Diloxanide Edetic acid Epinastine hydrochloride Ethosuximide Ethotoin Fenoprofen Ibuprofen Irbesartan Ketoprofen Lonazolac Mephenytoin Mepindolol Montelukast sodium Nabilone Oxymetazoline Paramethadione Pentorex Saquinavir Suprofen Thiamphenicol Tolmetin Trimazosin Zolpidem sodium cyanoborohydride... 

CH4N2O 57-13-6) see Alfuzosin Allantoin Amobarbital Barbital Bromisoval Butalbital Carbasalate calcium Carbromal Cyclopentobarbital Dimethadione Dipyridamole Enoximone Ethotoin Heptabarb Metaxalone Methyclothiazide Orotic acid Paramethadione Pentobarbital Phenacemide Phenetuiide Phenobarbital Phenytoin Proquazone Secbutabarbital Secobarbital Sulfadimethoxine Thalidomide Trimethadione... 

PAG , 111 Paludrine, 115 Pamaquine, 345 Papaverine, 347, 348 Para-aminobenzoic acid, in bacterial metabolism, 109, 121 Para-aminosalicylic acid, 109 Paraethoxycaine, 10, 11 Paramethadione, 232 Paramethasone, 200 Parasympathetic nervous system, 35, 62... 

From the chemical point of view, formally, antiepileptic drugs could be classified as derivatives of hydantoins (phenytoin, mephenytoin, ethotoin), barbiturates (phenobarbital, mephobarbital, and primidone), succinimides (ethosuximide, methosuximide, phensux-imide), benzodiazepines (diazepam, chlorodiazepoxide, clonazepam, lorazepam), oxazo-lidines (trimethadione, paramethadione), and also valproic acid, carbamazepine, and acetazolamide. 

Paramethadione Paramethadione, 5-ethyl-3,5-dimethyloxazolidine-2,4-dione (9.8.3), differs from trimethadione only in the substitution of one methyl group with an ethyl gronp. It is synthesized in a completely analogons manner, except that it comes from 2-hydroxy-2-methylbntyric acid instead of 2-hydroxyisobutyric acid [29]. 

Paramethadione is also used in minor forms of epilepsy. Paradione is a synonym of this drug. 

Trimethadione, the first oxazolidinedione (Figure 24-3), was introduced as an antiseizure drug in 1945 and remained the drug of choice for absence seizures until the introduction of succinimides in the 1950s. Use of the oxazolidinediones (trimethadione, paramethadione, and dimethadione) is now very limited. 

Medicinals derived from oxazole include the antiepileptic drugs trimethadione (320 R = Me) and paramethadione (320 R = Et) (80MI41802), the sedative and muscle-relaxant zoxazolamine (321), and furazolidone (322), which is effective against a wide range of enteric infections. Derivatives of oxazolidine show promise as appetite depressants (65MI41800). 

Gas Chromatography. System GA—RI 1120 system GE— paramethadione retention time 0.06, A -desmethylparametha-dione retention time 0.22, both relative to phenytoin. 

Half-life. Plasma half-life, paramethadione about 16 hours after a single dose, A-desmethylparamethadione about 7 to 14 days during chronic administration. 

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