デフェロキサミン
デフェロキサミン · N-ヒドロキシ-N-[1,4-ジオキソ-4-[5-(アセチルヒドロキシアミノ)ペンチルアミノ]ブチル]-N′-[1,4-ジオキソ-4-(5-アミノペンチルヒドロキシアミノ)ブチル]-1,5-ペンタンジアミン · N-(5-アミノペンチル)-N-ヒドロキシ-3-[5-[3-[5-(アセチルヒドロキシアミノ)ペンチルカルバモイル]プロパノイルヒドロキシアミノ]ペンチルカルバモイル]プロパンアミド · N-(5-アミノペンチル)-N-ヒドロキシ-N'-[5-(N-ヒドロキシ-3-{[5-(N-ヒドロキシアセトアミド)ペンチル]カルバモイル}プロパンアミド)ペンチル]ブタンジアミド · N′-[5-[[4-[[5-(アセチルヒドロキシアミノ)ペンチル]アミノ]-1,4-ジオキソブチル]ヒドロキシアミノ]ペンチル]-N-(5-アミノペンチル)-N-ヒドロキシブタンジアミド · デフェリオキサミン · N-(5-アミノペンチル)-4-[5-[ヒドロキシ[3-[5-(アセチルヒドロキシアミノ)ペンチルカルバモイル]プロピオニル]アミノ]ペンチルアミノ]-4-オキソブタンヒドロキサム酸 · N-[5-[アセチル(ヒドロキシ)アミノ]ペンチル]-N′-ヒドロキシ-N′-[5-[4-[5-アミノペンチル(ヒドロキシ)アミノ]-1,4-ジオキソブチルアミノ]ペンチル]ブタンジアミド
識別子と物理属性
| CAS No. | 70-51-9 |
|---|---|
| 分子式 | C25H48N6O8 |
| 平均分子量 | 560.7 g/mol |
| 単同位体質量 | 560.3533625 g/mol |
| SMILES | CC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN |
| InChIKey | UBQYURCVBFRUQT-UHFFFAOYSA-N |
| PubChem CID | 2973 |
| ChEMBL | CHEMBL556 |
| ChEBI | CHEBI:4356 |
| EC No. | 200-738-5 |
| DTXSID | DTXSID7022887 |
| 現地名 | デフェロキサミン |
化学・物理的性質
| XLogP | -2.1 |
|---|---|
| 極性表面積 | 206 |
| 水素結合供与体数 | 6 |
| 水素結合受容体数 | 9 |
| 回転可能結合数 | 23 |
| 重原子数 | 39 |
| 形式電荷 | 0 |
| 複雑度 | 739 |
| 医薬品 | Pharmaceuticals -> Listed in ZINC15 |
| 脂質 | Fatty Acyls [FA] -> Fatty amides [FA08] -> N-acyl amines [FA0802] |
| LogP（分配係数） | -2.2-1.52 |
| 溶解度 | 9.90e-02 g/L |
| Human Drugs | Breast FeedingLactationChelating AgentsIron Chelating AgentsAntidotes and other substances used in poisonings > Specific |
| 融点 | MP: 138-140 °C /MONOHYDRATE/172-175 °C /HYDROCHLORIDE/148-149 °C /METHANESULFONATE/MP: 180-182 °C /N-ACETYL DERIV/138 - 140 °C139°C |
| Physical Description | Solid |
| Stability/Shelf Life | RECONSTITUTED SOLN ARE STABLE FOR 2 WK @ ROOM TEMP /MESYLATE/ |
| Collision Cross Section | 228.86 Ų [M+Na]+ [CCS Type: TWMethod: calibrated with polyalanine and drug standards] |
| Other Experimental Properties | CRYSTALS FROM DIL ALC /MONOHYDRATE/CRYSTALS FROM SLIGHTLY ACIDIC METHANOL /HYDROCHLORIDE/CRYSTALS FROM DIL ALC /METHANESULFONATE/CRYSTALS FROM N-PROPANOL /N-ACETYL DERIV/ |
| 沸点 | 627.9°C (rough estimate) |
| 密度 | 1.2216 (rough estimate) |
| 屈折率 | 1.5540 (estimate) |
| 貯蔵条件 | -20°C |
| 外観・状態 | Solid |
| pKa（酸解離定数） | 9.08±0.50(Predicted) |
| 色 | White to off-white |
| 主な用途 | 医薬品 |
| InChIKey | UBQYURCVBFRUQT-UHFFFAOYSA-N |
| SMILES | C(=O)(N(O)CCCCCNC(=O)CCC(=O)N(O)CCCCCN)CCC(=O)NCCCCCN(O)C(=O)C |
| EPAの化学物質情報 | Deferoxamine (70-51-9) |
安全性と法規制
| GHS 分類 | WarningH302 (97.1%): Harmful if swallowed [Warning Acute toxicity, oral]P264, P270, P301+P317, P330, and P501 (click each P-code to see the statement)Aggregated GHS information provided per 69 reports by companies from 3 notifications to the ECHA C&L Inventory. |
|---|---|
| 規制情報 | Status: Active Update: 07-06-2016 https://echa.europa.eu/registration-dossier/-/registered-dossier/17782 |
| Hazard Classes and Categories | Acute Tox. 4 (97.1%) |
| 相互作用 | THE CONCOMITANT ORAL ADMINISTRATION OF ASCORBIC ACID (0.5 TO 1 G TWICE DAILY) SEEMS TO IMPROVE THE CHELATING ACTION OF DEFEROXAMINE IN HEMOCHROMATOSIS, PARTICULARLY IF THERE IS A VITAMIN C DEFICIENCY. |
| Hepatotoxicity | In large clinical trials, elevations in serum aminotransferase levels were rare in patients receiving deferoxamine and instances of acute, clinically apparent liver injury were not reported. Patients with transfusion related iron overload often have concurrent chronic hepatitis B or C, and elevations of serum aminotransferase levels during chelation therapy may be due to natural fluctuations in the underlying chronic liver disease activity. Nevertheless, elevations in serum aminotransferase levels and “hepatic dysfunction” are listed as potential adverse events in product labels for deferoxamine. After an early report of hepatitis occurring in patient on hemodialysis receiving deferoxamine to reduce aluminum levels, there have been no further published instances of clinically apparent liver injury that have been convincingly linked to deferoxamine therapy. |
| 有害作用 | Chronic deferoxamine therapy can lead to sensorineural hearing loss and retinopathy. Though the mechanism of ocular injury is not well understood, it appears to partially occur due to damage to the retinal pigment epithelium, which can lead to decreased visual acuity, visual field defects, and color vision defects. Hearing and vision loss can be reversible if the patient discontinues the drug early in the course. Growth retardation can also occur in children receiving deferoxamine treatment, and clinicians should monitor patients for appropriate growth velocity over time. |
| 毒性の概要 | Patients tolerate deferoxamine well, and there is no specific antidote for the medication. The precautions and dose reductions are described elsewhere in this paper. |
| Human Toxicity Excerpts |
用途
説明
Deferoxamine was introduced in the 1960s for chelation of iron. It is synthesized by removing a central iron molecule from ferrioxamine B, a compound obtained from the microorganism Streptomyces pilosus. Deferoxamine binds to iron from ferritin and forms ferrioxamine, a very stable and water-soluble chelate with a characteristic reddish color.
使用
Deferoxamine is used for the treatment of both acute iron intoxication and chronic iron overload due to transfusiondependent anemias. It has also been used in trials for malaria treatment and for aluminum chelation in hemodialysis patients. 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.