(2R,3S)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid

• ChemBase ID: 4422
• Molecular Formular: C9H11NO5
• Molecular Mass: 213.18734
• Monoisotopic Mass: 213.06372246
• SMILES: O[C@H]([C@@H](N)C(=O)O)c1cc(O)c(O)cc1
• Canonical SMILES: OC(=O)[C@@H]([C@H](c1ccc(c(c1)O)O)O)N
• InChI: InChI=1S/C9H11NO5/c10-7(9(14)15)8(13)4-1-2-5(11)6(12)3-4/h1-3,7-8,11-13H,10H2,(H,14,15)/t7-,8+/m1/s1
• InChIKey: QXWYKJLNLSIPIN-SFYZADRCSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (2R,3S)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid
• IUPAC Traditional name: droxidopa
• Brand Name: Dops
• Synonyms: threo-3,4-DIHYDROXY PHENYL SERINE; L-threo-3,4-dihydroxyphenylserine; L-DOPS; L-dihydroxyphenylserine; Droxydopa; Droxidopa

Database IDs

• CAS Number: 23651-95-8
• PubChem SID: 160967854; 99443239
• PubChem CID: 443940

CALCULATED PROPERTIES

JChem

• Acid pKa: 1.4644188
• H Acceptors: 6
• H Donor: 5
• LogD (pH = 5.5): -2.7111156
• LogD (pH = 7.4): -2.7307446
• Log P: -2.7110136
• Molar Refractivity: 50.2856 cm^3
• Polarizability: 19.837856 Å^3
• Polar Surface Area: 124.01 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -2.37
• LOG S: -1.14
• Solubility (Water): 1.53e+01 g/l

DETAILS

MP Biomedicals - 05222549

MP Biomedicals Rare Chemical collection

DrugBank - DB06262

• Drug Groups: approved; investigational
• Description: Droxidopa is a precursor of noradrenaline that is used in the treatment of Parkinsonism. It is approved for use in Japan and is currently in trials in the U.S. The racaemic form (dl-threo-3,4-dihydroxyphenylserine) has also been used, and has been investigated in the treatment of orthostatic hypotension. There is a deficit of noradrenaline as well as of dopamine in Parkinson's disease and it has been proposed that this underlies the sudden transient freezing seen usually in advanced disease.
• Indication: For treatment of neurogenic orthostatic hypotension (NOH) associated with various disorders including Multiple System Atrophy, Familial Amyloid Polyneuropathy, hemodialysis induced hypotension and Parkinson's Disease. Also investigated for use/treatment in neurologic disorders, nephropathy, blood (blood forming organ disorders, unspecified), and dizzy/fainting spells.
• Pharmacology: Droxidopa is an orally active synthetic precursor of norepinephrine that increases the deficient supply of norepinephrine in patients with NOH, thereby improving orthostatic blood pressure and alleviating associated symptoms of lightheadedness, dizziness, blurred vision, and syncope through the induction of tachycardia (increased heart rate) and hypertension.
• Toxicity: Droxidopa has minimal toxic effects and an acute, oral LD50 of more than 5 g/kg in mice, rats, dogs, and monkeys. Side effects occur in in 0.78% of patients and include nausea, headache, increased blood pressure, hallucination, and anorexia.
• Affected Organisms: Humans and other mammals
• Biotransformation: Droxidopa is metabolized by aromatic L-amino acid decarboxylase.
• Absorption: Oral bioavailability is 90%.
• Half Life: 2-3 hours.
• Elimination: Droxidopa is mainly excreted in the urine, with the main metabolite being 3-O-methyldihydroxyphenylserine.
• References: Kaufmann H: L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience. Clin Auton Res. 2008 Mar;18 Suppl 1:19-24. Epub 2008 Mar 27. [Pubmed] ; Balk SH, Yoshioka H, Yukawa H, Harayama S: Synthesis of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) with thermostabilized low-specific L-threonine aldolase from Streptomyces coelicolor A3(2). J Microbiol Biotechnol. 2007 May;17(5):721-7. [Pubmed] ; Mathias CJ: L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience. Clin Auton Res. 2008 Mar;18 Suppl 1:25-9. Epub 2008 Mar 27. [Pubmed] ; Goldstein DS: L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug. Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):189-203. [Pubmed] ; Goldstein DS, Holmes C, Kaufmann H, Freeman R: Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure. Clin Auton Res. 2004 Dec;14(6):363-8. [Pubmed] ; Goldstein DS: L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug. Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):189-203. [Pubmed]
• External Links: Wikipedia

REFERENCES

• Goldstein DS: L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug. Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):189-203. Pubmed
• Goldstein DS, Holmes C, Kaufmann H, Freeman R: Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure. Clin Auton Res. 2004 Dec;14(6):363-8. Pubmed
• Goldstein DS: L-Dihydroxyphenylserine (L-DOPS): a norepinephrine prodrug. Cardiovasc Drug Rev. 2006 Fall-Winter;24(3-4):189-203. Pubmed
• Kaufmann H: L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience. Clin Auton Res. 2008 Mar;18 Suppl 1:19-24. Epub 2008 Mar 27. Pubmed
• Balk SH, Yoshioka H, Yukawa H, Harayama S: Synthesis of L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS) with thermostabilized low-specific L-threonine aldolase from Streptomyces coelicolor A3(2). J Microbiol Biotechnol. 2007 May;17(5):721-7. Pubmed
• Mathias CJ: L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience. Clin Auton Res. 2008 Mar;18 Suppl 1:25-9. Epub 2008 Mar 27. Pubmed