50-12-4 Usage
Description
(S)-Mephenytoin, also known as Mesantoin, is a chiral anticonvulsant drug derived from the racemic mixture of mephenytoin. It is characterized by the N-methylation at position 3 and the presence of an ethyl group replacing one of the phenyl substituents at position 5. (S)-Mephenytoin is indicated for the treatment of focal and Jacksonian seizures in patients who are refractory to less toxic antiepileptic drugs (AEDs). However, it is associated with an increased incidence of serious toxicities, such as severe rash, agranulocytosis, and hepatitis. Its N-desmethyl metabolite, 5-phenyl-5-ethylhydantoin, contributes to both its efficacy and toxicity. The drug is no longer commercially available in the United States but is still available outside the country. It is marketed under the brand name Mesantoin by Novartis.
Uses
Used in Pharmaceutical Industry:
(S)-Mephenytoin is used as an anticonvulsant agent for the treatment of focal and Jacksonian seizures in patients who are refractory to less toxic AEDs. It is particularly useful in cases where safer drugs have failed to provide the desired therapeutic effects. However, its use is limited due to the potential for severe toxicities, such as severe rash, agranulocytosis, and hepatitis.
Used in Research and Development:
(S)-Mephenytoin can be utilized in research and development for the study of its pharmacological properties, mechanisms of action, and potential applications in the treatment of various neurological disorders. This may include investigations into its interactions with other drugs, its metabolism, and the development of novel drug delivery systems to improve its efficacy and safety profile.
Originator
Mesantoin,Sandoz
Manufacturing Process
23 parts sodium was dissolved in 300 parts of ethanol and added to 160 parts of 5-phenylcyanacetamide in 750 parts of ethanol. A mixture was cooled straight away and a sodium salt of amide precipitated as a white powder. 200 parts of ethyl iodide was added to this mixture and heated for 1.5 hours. The ethanol was distilled off, water was added to the residue and rapidly hardened oil precipitated. After recrystallization from ethanol, 5-ethyl-5- phenylacetamide afforded; MP: 116°C.100 parts of sodium hydroxide was solved in 500 parts of water and added to
83 parts of bromine by cooling. 5-Ethyl-5-phenylacetamide was added to
above prepared mixture. It dissolved quickly, whereupon all mass was heated
some time, cooled and stood at room temperature some hours. Then a
solution of sodium bisulfite was added before the formed precipitate dissolved.
The reaction mixture was filtered, the filtrate was acidified to give rapidly
hardened oil. After recrystallization from ethanol 5-ethyl-3-methyl-5-phenylhydantoin was yielded as the bright needles; MP: 201°-202°C.
Therapeutic Function
Anticonvulsant, Antiepileptic
Biological Activity
CYP2C19 substrate. Anticonvulsant.
Biochem/physiol Actions
CYP2B6 and CYP2C19 substrate; anticonvulsive, antiepileptic.
Safety Profile
Poison by ingestion and
intraperitoneal routes. Human systemic
effects by ingestion: somnolence,
hemorrhage, changes in teeth and
supporting structures. Human mutation data
reported. An experimental teratogen. An
FDA proprietary drug used as an
anticonvulsant. When heated to
decomposition it emits toxic fumes of NOx.
Check Digit Verification of cas no
The CAS Registry Mumber 50-12-4 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 0 respectively; the second part has 2 digits, 1 and 2 respectively.
Calculate Digit Verification of CAS Registry Number 50-12:
(4*5)+(3*0)+(2*1)+(1*2)=24
24 % 10 = 4
So 50-12-4 is a valid CAS Registry Number.
InChI:InChI=1/C12H14N2O2/c1-3-12(9-7-5-4-6-8-9)10(15)14(2)11(16)13-12/h4-8H,3H2,1-2H3,(H,13,16)
50-12-4Relevant articles and documents
Pseudoephedrine-Directed Asymmetric α-Arylation of α-Amino Acid Derivatives
Atkinson, Rachel C.,Fernández-Nieto, Fernando,Mas Rosell?, Josep,Clayden, Jonathan
supporting information, p. 8961 - 8965 (2015/08/03)
Available α-amino acids undergo arylation at their α position in an enantioselective manner on treatment with base of N′-aryl urea derivatives ligated to pseudoephedrine as a chiral auxiliary. In situ silylation and enolization induces diastereoselective migration of the N′-aryl group to the α position of the amino acid, followed by ring closure to a hydantoin with concomitant explulsion of the recyclable auxiliary. The hydrolysis of the hydantoin products provides derivatives of quaternary amino acids. The arylation avoids the use of heavy-metal additives, and is successful with a range of amino acids and with aryl rings of varying electronic character.
Intramolecular arylation of amino acid enolates
Atkinson, Rachel C.,Leonard, Daniel J.,Maury, Julien,Castagnolo, Daniele,Volz, Nicole,Clayden, Jonathan
supporting information, p. 9734 - 9736 (2013/10/21)
Dianionic enolates formed from N′-aryl urea derivatives of amino acids undergo intramolecular C-arylation by attack of the enolate anion on the N′-aryl ring, leading to a hydantoin derivative of a quaternary amino acid. In situ IR studies allow identification of four intermediates on the reaction pathway.
Chromatographic Resolutions of Racemates, XI. Comparison of Optically Active Polyamides and Cellulose Triacetate
Blaschke, Gottfried,Kraft, Horst Peter,Markgraf, Hildegunde
, p. 3611 - 3617 (2007/10/02)
On optically active polyacrylic and polymethacrylic amides (1a-e) as well as on microcrystalline cellulose triacetate (2), numerous racemates including drugs are separated at least partially, the amide 4f completely on cellulose triacetate.By repeated chromatography on the polyamide 1a, (+)- and (-)-mandelic acid (4a) and (+)-hexobarbital (9d) also were obtained optically pure.
