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

• ChemBase编号: 4422
• 分子式: C9H11NO5
• 平均质量: 213.18734
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: (2R,3S)-2-amino-3-(3,4-dihydroxyphenyl)-3-hydroxypropanoic acid
• IUPAC传统名: droxidopa
• 商标名: Dops
• 别名: threo-3,4-DIHYDROXY PHENYL SERINE; L-threo-3,4-dihydroxyphenylserine; L-DOPS; L-dihydroxyphenylserine; Droxydopa; Droxidopa

登记号

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

理论计算性质

JChem

• Acid pKa: 1.4644188
• 质子受体: 6
• 质子供体: 5
• LogD (pH = 5.5): -2.7111156
• LogD (pH = 7.4): -2.7307446
• Log P: -2.7110136
• 摩尔折射率: 50.2856 cm^3
• 极化性: 19.837856 Å^3
• 极化表面积: 124.01 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: -2.37
• LOG S: -1.14
• 溶解度: 1.53e+01 g/l

详细说明

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

参考文献

• 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