Pyridoxamine dihydrochloride Chemical Properties

Melting point:

224-226 °C (dec.)(lit.)

Density 

1.4025 (rough estimate)

refractive index 

1.6100 (estimate)

storage temp. 

Inert atmosphere,Store in freezer, under -20°C

solubility 

DMSO (Slightly), Methanol (Slightly), Water (Slightly)

form 

Powder or Solid

pka

pKa 3.31(H2O t = 25 I = 0.1)(Approximate)

color 

White to off-white to pale brown

biological source

synthetic (organic)

Water Solubility 

Soluble in DMSO, water, or methanol /n

Merck 

7980

BRN 

3632748

InChI

InChI=1S/C8H12N2O2.2ClH/c1-5-8(12)7(2-9)6(4-11)3-10-5;;/h3,11-12H,2,4,9H2,1H3;2*1H

InChIKey

HNWCOANXZNKMLR-UHFFFAOYSA-N

SMILES

C1(CN)=C(O)C(=NC=C1CO)C.Cl.Cl

CAS DataBase Reference

524-36-7(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

WGK Germany 

2

RTECS 

UV1230000

HazardClass 

IRRITANT

HS Code 

29333990

Toxicity

cat,LD50,intravenous,540mg/kg (540mg/kg),GASTROINTESTINAL: CHANGES IN STRUCTURE OR FUNCTION OF SALIVARY GLANDSBEHAVIORAL: CONVULSIONS OR EFFECT ON SEIZURE THRESHOLDGASTROINTESTINAL: "HYPERMOTILITY, DIARRHEA",Arzneimittel-Forschung. Drug Research. Vol. 11, Pg. 922, 1961.

MSDS

• Language:English Provider:Pyridoxamine dihydrochloride
• Language:English Provider:SigmaAldrich

Pyridoxamine dihydrochloride Usage And Synthesis

Description

Pyridoxamine dihydrochloride is a salt and amine form of pyridoxamine, which belongs to the family of vitamin B6 compounds. Pyridoxamine occurs naturally in animal-based food products. Its deficiency in humans potentially causes sideroblastic anemia, weakness, insomnia, and neurological disorders. It has been reported to be effective against diabetic nephropathy. Pyridoxamine dihydrochloride acts as a catalyst in the metabolism of fats, carbohydrates, and proteins in the body, thereby assisting in maintaining energy balance in kidney disease patients.

Chemical Properties

It is a white to yellowish crystal or crystalline powder that readily absorbs moisture. It is generally stable at room temperature but tends to change color when exposed to light. Its melting point is at 226-227℃, with decomposition. It exhibits maximum absorption at a wavelength of 287.5nm. The substance is soluble in water, slightly soluble in ethanol, but insoluble in ether or chloroform.

Uses

Pyridoxamine dihydrochloride (Pyridorin, NephroGenex, 524-36-7) inhibits formation of advanced glycation end products and scavenges reactive oxygen species and toxic carbonyls. Whether these effects translate into kidney protection is unknown, although a year-long study of the effects of pyridoxamine dihydrochlo-ride in patients with type 2 diabetes and proteinuria failed to show a difference in kidney function decline with pyri-doxamine dihydrochloride in daily doses of 300 or 600 mg versus placebo treatment.

Preparation

The procedure for preparing pyridoxamine dihydrochloride involves several steps: firstly enabling pyridoxal oxime to react with acetic acid and zinc to obtain acetic acid solution containing pyridoxamine, then decompressing the solution and reclaiming the acetic acid to obtain slurry concentrate, decompressing and reclaiming the acetic acid again to obtain pyridoxamine water solution, regulating the pH value to be alkaline so as to separate pyridoxamine out, adding water and hydrochloric acid after vacuum filteration, decoloring and filtering to obtain filtrate, decompressing and concentrating the filtrate until white solids are separated out, adding solvent and stirring, and finally crystallizing at the lower temperature, filtering and drying to obtain the pyridoxamine dihydrochloride.
CN101628892A

Definition

ChEBI: Pyridoxamine dihydrochloride is a hydrochloride obtained by combining pyridoxamine with two molar equivalents of hydrochloric acid. Used for treatment of diabetic nephropathy. It has a role as an Escherichia coli metabolite, a Saccharomyces cerevisiae metabolite, a human metabolite, a mouse metabolite, a plant metabolite, an iron chelator and a nephroprotective agent. It is a hydrochloride and a vitamin B6. It contains a pyridoxamine(2+).

Pharmacokinetics

The progression of diabetic nephropathy can be blocked by Pyridoxamine dihydrochloride, a derivative of vitamin B6, which is a potent inhibitor of AGE formation. However, it has been observed that this treatment is only effective in patients who have relatively preserved kidney function (baseline SCr 1.3 to 1.9 mg/dL).

Synthesis

The general procedure for the synthesis of 4-(aminomethyl)-5-hydroxy-6-methyl-3-pyridine methanol dihydrochloride (pyridoxamine dihydrochloride), using 2-methyl-3-hydroxy-4-cyano-5-acetoxymethylpyridine (CAS:408335-89-7) as starting material, was as follows: 214 mg (1.04 mmol) of 2-methyl-3-hydroxy- 4-cyano-5-acetoxymethylpyridine was dissolved in a 12 mol methanol solution containing 300 μL of 30% hydrochloric acid. To this solution was added 40 mg 5% w/w of palladium carbon catalyst, followed by hydrogenation reaction at atmospheric pressure and room temperature. Upon completion of the reaction, the catalyst was removed by filtration and the filtrate was concentrated under reduced pressure to remove the solvent. The resulting residue was purified by ethanol recrystallization to give 208 mg (0.86 mmol) of off-white solid pyridoxamine dihydrochloride in 83% yield. The structure of the product was analyzed by 1H NMR, 13C NMR, liquid chromatography (LC), liquid chromatography-mass spectrometry (LC/MS) and ultraviolet spectroscopy (UV), and confirmed by comparing the data with those of commercially available standards of pyridoxamine dihydrochloride.

Purification Methods

The amine salt is crystallised from hot MeOH. The free base crystallises from EtOH with m 193-193.5o [Harris et al. J Biol Chem 154 315 1944, J Am Chem Soc 66 2088 1944]. [Beilstein 22 IV 6064, 22/12 V 324.]

References

[1] Patent: WO2006/66806, 2006, A1. Location in patent: Page/Page column 16
[2] Patent: WO2013/167991, 2013, A1. Location in patent: Paragraph 00103; 00104
[3] Patent: US2015/141468, 2015, A1. Location in patent: Paragraph 0110; 0119; 0120

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