6055. Methyldopa

Nomenclature

CAS number: 555-30-6; 41372-08-1 (sesquihydrate)
3-Hydroxy-α-methyl-l-tyrosine; l-3-(3,4-dihydroxyphenyl)-2-methylalanine; l-α-methyl-3,4-dihydroxyphenylalanine; l-2-amino-2-methyl-3-(3,4-dihydroxyphenyl)propionic acid; l-α-methyldopa; MK-351; Aldomet (Merck & Co.); Dopamet (Actavis); Dopegyt (Egis); Medopren (Malesci); Presinol (Bayer).
C10H13NO4; mol wt 211.21.
C 56.87%, H 6.20%, N 6.63%, O 30.30%.

Description and references

Prepn of racemate: K. Pfister, G. A. Stein, US 2868818 (1959 to Merck & Co.). Resolution: R. T. Jones et al., US 3158648 (1964 to Merck & Co.); and configuration: E. W. Tristram et al., J. Org. Chem. 29, 2053 (1964). Synthesis from asymmetric intermediates: D. F. Reinhold et al., ibid. 33, 1209 (1968); J. L. León-Romo et al., Chirality 14, 144 (2002). HPLC determn in plasma: G. Bahrami et al., J. Chromatogr. B 832, 197 (2006). Clinical pharmacokinetics: E. Myhre et al., Clin. Pharmacokinet. 7, 221 (1982). Review of mechanism of action and pharmacology: E. D. Frohlich, Arch. Intern. Med. 140, 954-959 (1980); and clinical experience: A. Scriabine, Ed. in Pharmacology of Antihypertensive Drugs (Raven, New York, 1980) pp 43-54.

Chemical structure

Properties

White to yellowish-white, odorless, fine powder. Considerably hygroscopic. Crystals from water as the sesquihydrate, mp 302-304° (dec). [α]D25 3° (c = 2 in 0.1N HCl). uv max: 281 nm (ε 2780). Very sol in 3N HCl; slightly sol in alcohol. Practically insol in ether. Soly in water at 25°: ≈10 mg/ml. pH of satd aq soln about 5.0.

Derivative

dl-Form.

Nomenclature

CAS number: 55-40-3

Properties

Crystals from acetone, mp ≈300° (dec). Soly in water at 25°: ≈20 mg/ml.

Derivative

l-Form ethyl ester hydrochloride.

Nomenclature

CAS number: 2508-79-4
Methyldopate hydrochloride.
C12H18ClNO4; mol wt 275.73.
C 52.27%, H 6.58%, Cl 12.86%, N 5.08%, O 23.21%.

Description and references

Prepn: FR M2153 (1963 to Merck & Co.); of pharmaceutical dosage forms: A. D. Marcus, US 3230143 (1966 to Merck & Co.).

Properties

White, odorless crystalline powder. Freely sol in water, ethanol, methanol; slightly sol in chloroform. Practically insol in ether.

Therapeutic Category

Antihypertensive.

Keywords

Antihypertensive