(2S)-2-amino-3-(4-hydroxyphenyl)-2-methylpropanoic acid

• ChemBase ID: 645
• Molecular Formular: C10H13NO3
• Molecular Mass: 195.21512
• Monoisotopic Mass: 195.08954328
• SMILES: OC(=O)C(N)(Cc1ccc(O)cc1)C
• Canonical SMILES: Oc1ccc(cc1)CC(C(=O)O)(N)C
• InChI: InChI=1S/C10H13NO3/c1-10(11,9(13)14)6-7-2-4-8(12)5-3-7/h2-5,12H,6,11H2,1H3,(H,13,14)/t10-/m0/s1
• InChIKey: NHTGHBARYWONDQ-JTQLQIEISA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2S)-2-amino-3-(4-hydroxyphenyl)-2-methylpropanoic acid; 2-amino-3-(4-hydroxyphenyl)-2-methylpropanoic acid
• IUPAC Traditional name: metyrosine; AMPT
• Brand Name: Demser
• Synonyms: Metirosine; Methyltyrosine; Metyrosine; L-2-Methyl-3-(4-hydroxy-phenyl)alanine; α-Methyl-L-tyrosine; DL-2-Methyl-3-(4-hydroxyphenyl)alanine; L-AMPT; α-Methyl-L-tyrosine; L-2-Methyl-3-(4-hydroxyphenyl)alanine; L-α-Methyltyrosine; AMPT; α-Methyl-DL-tyrosine; (+/-)-α-Methyl-p-tyrosine; Racemetirosine; α-Methyltyrosine; α-Methyl-D,L-tyrosine; α-甲基-L-酪氨酸; α-甲基-L-酪氨酸; L-2-甲基-3-(4-羟基苯基)丙氨酸; L-α-甲基酪氨酸; DL-2-甲基-3-(4-羟基苯基)丙氨酸; α-甲基-DL-酪氨酸

Database IDs

• CAS Number: 620-30-4; 672-87-7; 658-48-0
• EC Number: 211-599-5; 211-523-0
• MDL Number: MFCD00064201; MFCD00004187
• Beilstein Number: 2368400; 2938704
• PubChem SID: 24278151; 160964108; 24278155; 46506079; 24885951
• PubChem CID: 441350

CALCULATED PROPERTIES

JChem

• Acid pKa: 2.0631347
• H Acceptors: 4
• H Donor: 3
• LogD (pH = 5.5): -1.0558071
• LogD (pH = 7.4): -1.0610021
• Log P: -1.0558642
• Molar Refractivity: 51.8105 cm^3
• Polarizability: 20.34689 Å^3
• Polar Surface Area: 83.55 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -1.91
• LOG S: -1.9
• Solubility (Water): 2.48e+00 g/l

PROPERTIES

Physical Property

• Solubility: Aqueous Sodium Hydroxide; Very slightly soluble; Water
• Apperance: White to Off-White Solid
• Melting Point: >280°C (dec.); >300 °C(lit.)
• Optical Rotation: [α]20/D -7°, c = 1 in 0.1 M HCl
• Hydrophobicity(logP): -1.7

Safety Information

• Storage Condition: Refrigerator
• RTECS: YP2890000
• German water hazard class: 3
• Personal Protective Equipment: Eyeshields, Gloves, type N95 (US), type P1 (EN143) respirator filter
• Storage Temperature: -20°C

Pharmacology Properties

• Gene Information: human ... TH(7054)

Product Information

• Purity: ≥95% (NT); ≥98% (TLC); ≥99.0% (TLC); 98%
• Ignition Residue: ≤0.05%
• Linear Formula: 4-(HO)C6H4CH2C(CH3)(NH2)CO2H
• Empirical Formula (Hill Notation): C10H13NO3

DETAILS

DrugBank - DB00765

• Drug Groups: approved
• Description: An inhibitor of the enzyme tyrosine 3-monooxygenase, and consequently of the synthesis of catecholamines. It is used to control the symptoms of excessive sympathetic stimulation in patients with pheochromocytoma. (Martindale, The Extra Pharmacopoeia, 30th ed)
• Indication: For use in the treatment of patients with pheochromocytoma, for preoperative preparation of patients for surgery, management of patients when surgery is contraindicated, and chronic treatment of patients with malignant pheochromocytoma.
• Pharmacology: In patients with pheochromocytoma, who produce excessive amounts of norepinephrine and epinephrine, administration of one to four grams of metyrosine per day has reduced catecholamine biosynthesis from about 35 to 80 percent as measured by the total excretion of catecholamines and their metabolites (metanephrine and vanillylmandelic acid). The maximum biochemical effect usually occurs within two to three days, and the urinary concentration of catecholamines and their metabolites usually returns to pretreatment levels within three to four days after metyrosine is discontinued. Most patients with pheochromocytoma treated with metyrosine experience decreased frequency and severity of hypertensive attacks with their associated headache, nausea, sweating, and tachycardia. In patients who respond, blood pressure decreases progressively during the first two days of therapy with metyrosine; after withdrawal, blood pressure usually increases gradually to pretreatment values within two to three days.
• Toxicity: Signs of metyrosine overdosage include those central nervous system effects observed in some patients even at low dosages. At doses exceeding 2000 mg/day, some degree of sedation or feeling of fatigue may persist. Doses of 2000-4000 mg/day can result in anxiety or agitated depression, neuromuscular effects (including fine tremor of the hands, gross tremor of the trunk, tightening of the jaw with trismus), diarrhea, and decreased salivation with dry mouth. The acute toxicity of metyrosine was 442 mg/kg and 752 mg/kg in the female mouse and rat respectively.
• Affected Organisms: Humans and other mammals
• Biotransformation: Little biotransformation, with catechol metabolites accounting for less than 1% of the administered dose.
• Absorption: Well absorbed from the gastrointestinal tract.
• Half Life: 3.4 to 3.7 hours
• Elimination: Because the first step is also the rate-limiting step, blockade of tyrosine hydroxylase activity results in decreased endogenous levels of catecholamines, usually measured as decreased urinary excretion of catecholamines and their metabolites.
• External Links: RxList; Drugs.com

Sigma Aldrich - M7628

Biochem/physiol Actions
酪氨酸羟化酶抑制剂。

Sigma Aldrich - M8131

Biochem/physiol Actions
Tyrosine hydroxylase inhibitor.
Other Notes
Active isomer
Packaging
1, 5 g in poly bottle
100, 250 mg in poly bottle

Sigma Aldrich - 120693

Biochem/physiol Actions
Tyrosine hydroxylase inhibitor.
Packaging
5, 25 g in glass bottle

Sigma Aldrich - 69577

Biochem/physiol Actions
Tyrosine hydroxylase inhibitor.
Other Notes
Inhibitor (Ki 5 uM) of tyrosine hydroxylase1

Sigma Aldrich - 69574

Biochem/physiol Actions
Tyrosine hydroxylase inhibitor.

Toronto Research Chemicals - M332685

A tyrosine hydroxylase inhibitor. An antihypertensive in pheochromocytoma.

REFERENCES

• Gilbert, J.A., et al.: Biochem. Pharmacol., 69, 1159 (2005)
• Morimoto, E., et al.: J. Pharmacol. Sci., 108, 505 (2005)