(2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid

• ChemBase ID: 843
• Molecular Formular: C10H13NO4
• Molecular Mass: 211.21452
• Monoisotopic Mass: 211.0844579
• SMILES: OC(=O)C(N)(Cc1cc(O)c(O)cc1)C
• Canonical SMILES: OC(=O)C(Cc1ccc(c(c1)O)O)(N)C
• InChI: InChI=1S/C10H13NO4/c1-10(11,9(14)15)5-6-2-3-7(12)8(13)4-6/h2-4,12-13H,5,11H2,1H3,(H,14,15)/t10-/m0/s1
• InChIKey: CJCSPKMFHVPWAR-JTQLQIEISA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2S)-2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid; 2-amino-3-(3,4-dihydroxyphenyl)-2-methylpropanoic acid
• IUPAC Traditional name: methyldopa; α methyldopa
• Brand Name: Aldoclor-150; Aldoclor-250; Aldomet; Aldometil; Aldomin; Aldoril 15; Aldoril 25; Aldoril D30; Aldoril D50; Apo-Methyldopa; Bayer 1440 L; Baypresol; Becanta; Dopamet; Dopamethyperpax; Dopatec; Dopegyt; Grospisk; Hyperpax; Hypolag; Medomet; Medopa; Medopal; Medopren; Methoplain; Novomedopa; Nu-Medopa; Presinol; Presolisin; Sedometil; Sembrina
• Synonyms: Alphamethyldopa; Alpha medopa; AMD; L-Methyl Dopa; Methyldopa anhydrous; Methyldopate; Methyldopate HCL; Mk. b51; Methyldopa; Aldoril; Dopamet; Dopegyt; MK-351; 3-(3,4-Dihydroxyphenyl)-2-methyl-L-alanine; Methyl-L-DOPA; Methyl-DOPA sesquihydrate; L-α-Methyl-DOPA; α-METHYL-L-β-3,4-DIHYDROXYPHENYLALANINE; 3-Hydroxy-α-methyltyrosine; 3-(3,4-Dihydroxyphenyl)-2-methylalanine; DL-α-Methyl DOPA; Metholes; Mulfasin; rac α-Methyl DOPA; 3-(3,4-二羟基苯基)-2-甲基-L-丙氨酸; L-甲基多巴; 甲基多巴 倍半水合物

Database IDs

• CAS Number: 555-30-6; 55-40-3; 41372-08-1
• EC Number: 209-089-2
• MDL Number: MFCD00004186
• Beilstein Number: 2417244
• PubChem SID: 46508535; 160964306; 24863565
• PubChem CID: 38853

CALCULATED PROPERTIES

JChem

• Acid pKa: 1.7286927
• H Acceptors: 5
• H Donor: 4
• LogD (pH = 5.5): -1.3594157
• LogD (pH = 7.4): -1.3670306
• Log P: -1.3594803
• Molar Refractivity: 53.7914 cm^3
• Polarizability: 20.989363 Å^3
• Polar Surface Area: 103.78 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -2.02
• LOG S: -1.97
• Solubility (Water): 2.26e+00 g/l

PROPERTIES

Physical Property

• Solubility: 1000 mg/L
• Melting Point: ≥300 °C
• Optical Rotation: [α]20/D -13.0±1°, c = 1% in H2O
• Hydrophobicity(logP): -1.7

Safety Information

• Storage Condition: 0°C; -20°C
• RTECS: AY5950000; YP2860000
• German water hazard class: 3
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter

Product Information

• Purity: ≥99.0% (sum of enantiomers, TLC)
• Salt Data: Free Base
• Impurities: ~12% water; ≤0.5% alanine
• Empirical Formula (Hill Notation): C10H13NO4 · 1.5H2O

DETAILS

MP Biomedicals - 02155519

(L-α-Methyl-DOPA) Crystalline

DrugBank - DB00968

• Drug Groups: approved
• Description: An alpha-2 adrenergic agonist that has both central and peripheral nervous system effects. Its primary clinical use is as an antihypertensive agent. [PubChem]
• Indication: For use in the treatment of hypertension.
• Pharmacology: Methyldopa is an aromatic-amino-acid decarboxylase inhibitor in animals and in man. Only methyldopa, the L-isomer of alpha-methyldopa, has the ability to inhibit dopa decarboxylase and to deplete animal tissues of norepinephrine. In man the antihypertensive activity appears to be due solely to the L-isomer. About twice the dose of the racemate (DL-alpha-methyldopa) is required for equal antihypertensive effect. Methyldopa has no direct effect on cardiac function and usually does not reduce glomerular filtration rate, renal blood flow, or filtration fraction. Cardiac output usually is maintained without cardiac acceleration. In some patients the heart rate is slowed. Normal or elevated plasma renin activity may decrease in the course of methyldopa therapy. Methyldopa reduces both supine and standing blood pressure. Methyldopa usually produces highly effective lowering of the supine pressure with infrequent symptomatic postural hypotension. Exercise hypotension and diurnal blood pressure variations rarely occur.
• Toxicity: The oral LD₅₀ of methyldopa is greater than 1.5 g/kg in both the mouse and the rat. Symptoms of overdose include bloating, constipation, diarrhea, dizziness, extreme drowsiness, gas, light-headedness, nausea, severely low blood pressure, slow heartbeat, vomiting, and weakness.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic, extensively metabolized. The known urinary metabolites are: a-methyldopa mono-0-sulfate; 3-0-methyl-a-methyldopa; 3,4-dihydroxyphenylacetone; a-methyldopamine; 3-0-methyl-a-methyldopamine and their conjugates.
• Absorption: Absorption from the gastrointestinal tract is variable but averages approximately 50%.
• Half Life: The plasma half-life of methyldopa is 105 minutes.
• Protein Binding: Low (less than 20%).
• Elimination: Methyldopa is extensively metabolized. The known urinary metabolites are: α-methyldopa mono-O-sulfate; 3-0-methyl-α-methyldopa; 3,4-dihydroxyphenylacetone; α-methyldopamine; 3-0-methyl-α-methyldopamine and their conjugates. Approximately 70 percent of the drug which is absorbed is excreted in the urine as methyldopa and its mono-O-sulfate conjugate. Methyldopa crosses the placental barrier, appears in cord blood, and appears in breast milk.
• Clearance: * Renal cl=130 mL/min [healthy]
• References: Mah GT, Tejani AM, Musini VM: Methyldopa for primary hypertension. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD003893. [Pubmed] ; McCoy S, Baldwin K: Pharmacotherapeutic options for the treatment of preeclampsia. Am J Health Syst Pharm. 2009 Feb 15;66(4):337-44. [Pubmed] ; Sica DA: Centrally acting antihypertensive agents: an update. J Clin Hypertens (Greenwich). 2007 May;9(5):399-405. [Pubmed] ; van Zwieten PA: Development and trends in the drug treatment of essential hypertension. J Hypertens Suppl. 1992 Dec;10(7):S1-12. [Pubmed] ; Rosenthal T, Oparil S: The effect of antihypertensive drugs on the fetus. J Hum Hypertens. 2002 May;16(5):293-8. [Pubmed] ; van Zwieten PA, Timmermans PB: Pharmacology and characterization of central alpha-adrenoceptors involved in the effect of centrally acting antihypertensive drugs. Chest. 1983 Feb;83(2 Suppl):340-3. [Pubmed] ; van Zwieten PA: Pharmacology of centrally acting hypotensive drugs. Br J Clin Pharmacol. 1980;10 Suppl 1:13S-20S. [Pubmed]
• External Links: Wikipedia; RxList; PDRhealth; Drugs.com

Selleck Chemicals - S1642

Research Area: Neurological Disease
Biological Activity:
Methyldopa (Aldomet) is a DOPA decarboxylase competitive inhibitor with an ED50 of 21.8 mg/kg. It is also known as aromatic L-amino acid decarboxylase, which converts L-DOPA into dopamine. Dopamine is a precursor for norepinephrine (noradrenaline) and subsequently epinephrine (adrenaline). This inhibition results in reduced dopaminergic and adrenergic neurotransmission in the peripheral nervous system. [1] The antihypertensive agents lofexidine (ED50, 0.03 mg/kg), guanabenz (ED50, 0.019 mg/kg), p-aminoclonidine (ED50, 0.23 mg/kg), methyldopa (ED50, 21.8 mg/kg), hydralazine (ED50, 0.98 mg/kg), prazosin (ED50, 0.72 mg/kg), minoxidil (ED50, 12.4 mg/kg) and pergolide (ED50, 0.021 mg/kg) were generalized to clonidine in a dose-dependent manner. [2] Methyldopa (Aldomet) is a psychoactive molecule used as a sympatholytic or antihypertensive.o

Sigma Aldrich - 37862

Other Notes
Antibacterial properties1

Toronto Research Chemicals - M303800

Antihypertensive agent.

REFERENCES

• Mah GT, Tejani AM, Musini VM: Methyldopa for primary hypertension. Cochrane Database Syst Rev. 2009 Oct 7;(4):CD003893. Pubmed
• McCoy S, Baldwin K: Pharmacotherapeutic options for the treatment of preeclampsia. Am J Health Syst Pharm. 2009 Feb 15;66(4):337-44. Pubmed
• Sica DA: Centrally acting antihypertensive agents: an update. J Clin Hypertens (Greenwich). 2007 May;9(5):399-405. Pubmed
• van Zwieten PA: Development and trends in the drug treatment of essential hypertension. J Hypertens Suppl. 1992 Dec;10(7):S1-12. Pubmed
• Rosenthal T, Oparil S: The effect of antihypertensive drugs on the fetus. J Hum Hypertens. 2002 May;16(5):293-8. Pubmed
• van Zwieten PA, Timmermans PB: Pharmacology and characterization of central alpha-adrenoceptors involved in the effect of centrally acting antihypertensive drugs. Chest. 1983 Feb;83(2 Suppl):340-3. Pubmed
• van Zwieten PA: Pharmacology of centrally acting hypotensive drugs. Br J Clin Pharmacol. 1980;10 Suppl 1:13S-20S. Pubmed
• http://en.wikipedia.org/wiki/Methyldopa
• Beckett, et al.: J. Pharm. Pharmacol., 7, 433 (1955)
• Sletzinger, et al.: J. Med. Chem., 6, 101 (1955)