70-51-9 Usage
Uses
Used in Medical Applications:
Deferoxamine is used as a chelating agent for iron, specifically for the treatment of acute iron intoxication and chronic iron overload due to transfusion-dependent anemias. Its ability to bind and remove excess iron makes it a crucial component in managing iron-related health issues.
Used in Malaria Treatment Research:
Deferoxamine has been utilized in trials for malaria treatment, exploring its potential to combat the disease by targeting iron-related pathways in the malaria parasite.
Used in Hemodialysis Patients:
In hemodialysis patients, Deferoxamine serves as an aluminum chelator, helping to remove excess aluminum from the body and mitigating its toxic effects.
Used in Neurological Research:
Studies of a rat model of intracerebral hemorrhage have noted that deferoxamine treatment reduced oxidative stress from iron release, indicating a possible role in preventing damage associated with hemorrhagic strokes. This suggests a potential application in neurological research and treatment for conditions involving iron-induced oxidative stress.
Originator
Deferoxamine,Novartis,Germany
Manufacturing Process
O-Benzylhydroxylamine hydrochloride (4.7 g, 29.7 mmol) was mixed with 5
ml of water and 11 ml of methanol at 0°C and the pH adjusted to 4.7 using 6
N KOH. The aldehyde, 4-cyanobutanal (2.6 mL, 27 mmol) was added to the
hydroxylamine and the mixture allowed to warm to room temperature. The pH
was maintained by addition of further 6 N KOH. After 1 h, the reaction was
cooled to 0°C, and sodium cyanoborohydride (1.26 g, 20 mmol) was added.
The pH was adjusted to 3 and maintained by addition of saturated HCl in
methanol. When the pH stabilized, the reaction was warmed to room temperature and stirred for 3 h at a PH of 3. The reaction mixture was then
poured into ether and made basic with 6 N KOH. The aqueous layer was
extracted with ether (3x50 mL). The extracts were combined, washed with
brine, and dried over magnesium sulfate. The solvents were removed and the
resulting liquid distilled at 150°-151°C (0.6 mm) to give 4.65 g (84% of Obenzyl-N-(4-cyanobutyl)hydroxylamine. 2.8 g (13.7 mmol) of the above
prepared hydroxylamine in 23 ml of pyridine and 2.1 g (20.8 mmol) of
succcinic anhydride, initially heated at 100°C for 1.5 h then allowed to cool to
room temperature and stirred overnight. The pyridine was removed in vacuum
and the residue was dissolved in a minimal amount of chloroform, and the
residue was dissolved in ether, which was extracted three times with 20%
potassium bicarbonate (3x50 mL). The aqueous solutions were combined,
acidified, extracted with ether, dried, filtered and evaporated; the residue was
then chromotagraphed on silica gel to give 4.12 g (98%) of N-(4-cyanobutylN-(benzyloxy)succinamic acid.2.6 g (12.75 mmol) of O-benzyl-N-(4-cyanobutyl)hydroxylamine, 17.24 mL of
pyridine and 17.2 mL of acetic anhydride were stirred under argon at room
temperature for 24 h. Then the excess pyridine and acetic acid anhydride
were removed by vacuum. The resulting oil was taken up in chloroform, which
was extracted with 1 N HCl (2x50mL), washed with sodium bicarbonate and
brine, dried, over sodium sulfate, filtered and evaporated to give 3.4 g
(100%) of N-(4-cyanobutyl)-N-(benzyloxy)acetamide as a light oil. 1.4 g (5.7
mmol) of this product, 2.6 g Raney nickel, 15 ml of ammonia saturated
methanol and 4 ml of saturated ammonium hydroxide were cooled in a ice
bath and anhydrous ammonia was allowed to bubble through the solution for
10 min. The bottle was pressurized to 50 psi with hydrogen and shook for 3 h.
Then the catalyst was filtered and the solvents evaporated. The crude material
was chromatografed on silica gel to gave a 1.25 g (88%) of N-(5-
aminopentyl)-N-(benzyloxy)acetamide.1 g (4 mmol), of the above acetamide, 1.46 g (4.79 mmol) of N-(4-
cyanobutyl-N-(benzyloxy)succinamic acid, 1.24 g (6 mmol) of DCC and 70 mg
of DMAP was cooled to 0°C for 0.55 h in 28 mL of chloroform. The mixture
was allowed to warm to room temperature and stirred 24 h. Then it was again
cooled to 0°C, filtered and chromatografed to yield 2.1 g (98%) of N-(4-
cyanobutyl)-3-[{5-N-benzyloxy)acetamido)pentyl}carbomoyl]-Obenzylpropionohydroxamic acid. This product (1 g) was hydrogeneted by
analogue with N-(4-cyanobutyl)-N-(benzyloxy)acetamide using Nickel Raney
as catalyst to give 1 g (88%) N-(5-aminopentyl)-3-[{5-(N -
benzyloxyacetamido)pentyl}carbomoyl]-O-benzylpropionohydroxamic acid,
which produced by the reaction with DCC described above 0.78 g (88%) of N-
[5-[3-[{4-cyanobutyl)(benzyloxy)-carbomoyl]propionaminoamido]pentyl}-3-
[{5-(N-bebzyloxyacetamido)pentyl]-carbomoyl]-O-benzylpropionohydroxamic
acid. The purity of all products confirmed with1H-NMR and elemental
analyses. The last compound (0.165 g, 0.2 mmol) was reduced in methanol,
2.7 mL of 0.1 N HCl and 0.27 g of 10% Pd on C. The hydrogenation was
carried out at one atmosphere of hydrogene for 7.5 hrs. The solution was
filtered, the solvents were removed and the residue was washed with cold
methanol, and then chloroform to give 0.1 g (84%) of product. This material
had melting point 167°-168°C [Prelog, supra] and was identical to an
authentic sample by 300 MHz NMR [sample of deferrioxamine B supplied by
dr. Heirich H. Peter at Ciba-Geigy, Basel, Switzerland].
Environmental Fate
Localized infusion or injection site reactions may occur
with deferoxamine administration, such as pain, urticaria
and flushing of the skin. Hypersensitivity reactions have
been documented with both acute and chronic administration
of deferoxamine. Some of the more serious side effects
include infusion rate-related hypotension, renal insufficiency,
neurotoxicity, growth retardation, pulmonary
toxicity, and infections. Deferoxamine may induce venous
dilation when given at doses greater than 15 mg kg-1 h-1
leading to poor venous return, depressed cardiac output,
and eventually hypotension. Increased levels of histamine
have been noted during hypotensive episodes, although
pretreatment with antihistamines has not been shown to
stop the reaction. An acute decrease in glomerular filtration
rate and renal plasma flow secondary to hypotension is the
possible mechanism underlying the nephrotoxicity induced
by deferoxamine. Depletion of iron, translocation of copper,
and chelation of other trace elements including zinc may
interfere with critical iron-dependent enzymes, causing
oxidative damage within various tissues. These are possible
mechanisms thought to be responsible for deferoxamineinduced
neurotoxicity, growth retardation, and pulmonary
toxicity. In vitro studies have shown that deferoxamine
inhibits the synthesis of prostaglandin, hemoglobin, ferritin,
collagen, and DNA. The iron–deferoxamine complex, ferrioxamine,
is a growth factor for many bacteria and fungi.
Deferoxamine has been associated with Yersinia enterocolitica
overgrowth and fatal cases of mucormycosis with prolonged
therapy.
Check Digit Verification of cas no
The CAS Registry Mumber 70-51-9 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 7 and 0 respectively; the second part has 2 digits, 5 and 1 respectively.
Calculate Digit Verification of CAS Registry Number 70-51:
(4*7)+(3*0)+(2*5)+(1*1)=39
39 % 10 = 9
So 70-51-9 is a valid CAS Registry Number.
InChI:InChI=1/C25H48N6O8/c1-21(32)29(37)18-9-3-6-16-27-22(33)12-14-25(36)31(39)20-10-4-7-17-28-23(34)11-13-24(35)30(38)19-8-2-5-15-26/h37-39H,2-20,26H2,1H3,(H,27,33)(H,28,34)
70-51-9Relevant articles and documents
Convergent Synthesis of Macrocyclic and Linear Desferrioxamines
Chiu, Cheng-Hsin,Chung, Wen-Sheng,Jheng, Ting-Cian,Mong, Kwok-Kong Tony,Peng, Bo-Chun
, (2020/06/17)
Polyhydroxamate desferrioxamines (DFO) are nontoxic siderophores endowed with high potential for development of therapeutic chelating agents. Herein, we report a modular and convergent strategy for diverse synthesis of macrocyclic and linear DFOs. The strategy employed orthogonally protected N-hydroxy-N-succinylcadaverine building blocks, which allowed bidirectional extension of the DFO structure. The efficiency of the new strategy was demonstrated by the total synthesis of 44-membered macrocyclic DFO-T1, as well as four related DFO compounds in 11–13 linear steps and 2.1 %–10 % overall yields. Comparison of the iron binding affinity of the DFOs revealed DFO-E as the best chelator.
Engineering a cleavable disulfide bond into a natural product siderophore using precursor-directed biosynthesis
Richardson-Sanchez, Tomas,Codd, Rachel
, p. 9813 - 9816 (2018/09/10)
An analogue of the bacterial siderophore desferrioxamine B (DFOB) containing a disulfide motif in the backbone was produced from Streptomyces pilosus cultures supplemented with cystamine. Cystamine competed against native 1,5-diaminopentane during assembly. DFOB-(SS)1[001] and its complexes with Fe(iii) or Ga(iii) were cleaved upon incubation with dithiothreitol. Compounds such as DFOB-(SS)1[001] and its thiol-containing cleavage products could expand antibiotic strategies and Au-S-based nanotechnologies.
Glycation Cross-link Breakers to Increase Resistance to Enzymatic Degradation
-
, (2013/12/03)
The present invention relates to a method to treat a grafts, implant, scaffold, and constructs, including allografts, xenografts, autografts, and prosthetics comprising collagen, with an inhibitor of collagen cross-links and/or advanced glycation endproducts (AGE), in order to alleviate the mechanical weakness induced by the cross-links The invention also provides for kits for use in the operating theater during autograft, allograft or xenograft procedures, or for preparing allograft, xenografts or prosthetics that have not been already treated prior to packaging. The kit comprises a first agent or agents that inhibit collagen cross-links and/or advanced glycation endproducts, instructions for use, optionally a wash or rinse agent, and a device for containing the graft and first agent.
Polymers with structure-defined functions
-
, (2011/06/23)
An alternating copolymer comprising a backbone of residues of a maleic anhydride derivative and those of a compound containing vinylic unsaturation, which also comprises residues of an active compound containing a nucleophilic group, bound to the backbone by a residue of the nucleophilic group, including such copolymer comprising residues of an active compound containing alcohol, thiol or amine group. The chemical and biological propertieis of actives, such as protease inhibitors, neurotransmitter drugs, and other small molecule active drugs, are enhanced, and new applications enabled. Also, artefacts, including a solid medical implant device, dressing or scaffold or a fluid adhesive or medicinal composition comprising such a polymer, and a method of use of such polymer, including a method for the treatment or prophylaxis of wounds
Imaging of Enzyme Activity
-
, (2008/06/13)
This invention relates to biochemistry and magnetic resonance imaging.
Multistage process for the preparation of highly pure deferoxamine mesylate salt
-
, (2008/06/13)
The present invention provides a purification process whereby deferoxamine B produced by a microorganism and in mixture with other polyhydroxamates produced by the microorganism may be converted into its mesylate salt substantially free of the other polyhydroxamates and substantially free of chloride ion. The process includes adsorption and desorption of the deferoxamine B on an adsorption resin, direct precipitation of the deferoxamine free base out of the eluent from the adsorption resin, contacting of the deferoxamine B free base with methanesulfonic acid and isolation of the deferoxamine B mesylate salt by precipitation. This process minimizes decomposition of deferoxamine B.
Stable freeze-dried pharmaceutical formulation
-
, (2008/06/13)
The subject of the invention is a freeze-dried formulation consisting of an amorphous phase and a crystalline phase, which is pharmaceutically acceptable, comprising at least one nonprotein active ingredient, characterized in that it contains mannitol and alanine in a ratio R of between 0.1 and 1, R representing the mass of mannitol to the mass of alanine.
Synthesis and biological evaluation of hydroxamate-based iron chelators
Bergeron,Wiegand,McManis,Perumal
, p. 3182 - 3187 (2007/10/02)
A new and versatile route to desferrioxamine B (DFO, 1) is described. Hydroxamate reagent 4 was elaborated in a series of high yield steps to the tert-butoxycarbonyl nitrile 11, which provided DFO in three transformations. The intermediate 11 could also be utilized in the preparation of DFO analogues which contain terminal N-acyl groups other than acetyl. The methodology was further employed in the syntheses of the DFO polyether analogues 2 and 3, beginning with the 3,6,9-trioxadecylation of N-(tert- butoxycarbonyl)-O-benzylhydroxylamine. Polyethers 2 and 3 are neutral molecules, which are somewhat more lipophilic than the parent DFO. Polyether hydroxamate 2 was shown to be nearly 3 times as effective as desferrioxamine at clearing iron in rats.
Pharmaceutical compositions containing a zinc complex
-
, (2008/06/13)
The invention provides a pharmaceutical composition comprising a zinc complex of desferrioxamine or penicillamine as active ingredient therein in combination with a pharmacologically acceptable carrier.
![N-[5-({3-[5-(acetyl-hydroxy-amino)-pentylcarbamoyl]-propionyl}-hydroxy-amino)-pentyl]-N'-hydroxy-N'-{5-[3-(4-isothiocyanato-phenyl)-thioureido]-pentyl}-succinamide](http://file1.lookchem.com/cas/reactions/2021/07/20/20380992.svg+xml_ms)
