ヒドロキシ尿素 化学特性,用途語,生産方法
外観
白色〜わずかにうすい赤褐色, 結晶〜結晶性粉末又は塊
溶解性
水に溶けやすく、エタノールに溶ける。
用途
DNAの合成阻害剤、同調培養用試薬、有機合成原料。
用途
DNA 合成に特異的な代謝過程
においてヌクレオシド二りん酸還元酵素を阻
害し、DNA 複製阻害作用を示します
効能
抗悪性腫瘍薬, 代謝拮抗薬
商品名
ハイドレア (ブリストル・マイヤーズスクイブ)
使用上の注意
潮解性あり。
化学的特性
Off-White Crystalline Solid
使用
An anti-neoplastic - inhibits ribonucleoside reductase and DNA replication. A potential therapy for sickle cell anemia which involves the nitrosylation of sickle cell hemoglobin. Horseradish peroxidase catalyzes nitric oxide formation from hydroxyurea in the presence of hydrogen peroxide.
適応症
Hydroxyurea (Hydrea) inhibits the enzyme ribonucleotide
reductase and thus depletes intracellular pools
of deoxyribonucleotides, resulting in a specific impairment
of DNA synthesis. The drug therefore is an Sphase
specific agent whose action results in an accumulation
of cells in the late G1- and early S-phases of the
cell cycle.
一般的な説明
HONH-CO-NH
2. The drug is available in a 500-mg capsulefor oral use. Hydroxyurea is often considered an antimetabolitedrug, and it is used to treat myelogenousleukemia, ovarian cancer, and essential thrombocytosis. Themechanism of action of hydroxyurea involves inhibition ofDNA biosynthesis by inhibition of the enzyme ribonucleotidereductase). Resistance can occur viaincreased expression of ribonucleotide reductase. The oralbioavailability is quite high approaching 100% and the drugis distributed to all tissues. Hydroxyurea readily enters theCNS and distributes to human breast milk. A major portionof the total dose is excreted unchanged in the urine. Thedrug has been shown to increase the toxicity of 5-FU, andhydroxyurea may increase the effectiveness of some antimetaboliteHIV drugs. The toxicity profile includes myelosuppression,leucopenia, nausea, vomiting, pruritus hyperpigmentation,headache, drowsiness, and confusion.
空気と水の反応
Water soluble.
反応プロフィール
An amide. Amides/imides react with azo and diazo compounds to generate toxic gases. Flammable gases are formed by the reaction of organic amides/imides with strong reducing agents. Amides are very weak bases (weaker than water). Mixing amides with dehydrating agents such as P2O5 or SOCl2 generates the corresponding nitrile. The combustion of these compounds generates mixed oxides of nitrogen (NOx).
火災危険
Flash point data for Hydroxyurea are not available; however, Hydroxyurea is probably combustible.
作用機序
Hydroxyurea is rapidly absorbed after oral administration,
with peak plasma levels achieved approximately
1 to 2 hours after drug administration; its elimination half-life is 2 to 3 hours. The primary route of excretion
is renal, with 30 to 40% of a dose excreted unchanged.
臨床応用
Hydroxyurea is used for the rapid lowering of blood
granulocyte counts in patients with chronic granulocytic
leukemia. The drug also can be used as maintenance
therapy for patients with the disease who have become
resistant to busulfan. Only a small percentage of patients
with other malignancies have had even brief remissions
induced by hydroxyurea administration.
副作用
Hematological toxicity, with white blood cells affected
more than platelets, may occur. Megaloblastosis
of the bone marrow also may be observed. Recovery is
rapid, generally within 10 to 14 days after discontinuation
of the drug. Some skin reactions, including hyperpigmentation
and hyperkeratosis, have been reported
with chronic treatment.
代謝
Hydroxyurea has excellent oral bioavailability (80–100%), and serum levels peak within 2 hours of consuming the capsules. If a positive response is noted within 6 weeks, toxicities generally are mild enough to permit long-term or indefinite therapy on either a daily or every-3-day basis. Leukopenia and, less commonly, thrombocytopenia and/or anemia are the most serious adverse effects. Excretion of the unchanged drug and the urea metabolite is via the kidneys. The carbon dioxide produced as a by-product of hydroxyurea metabolism is excreted in the expired air.
純化方法
Recrystallise hydroxyurea from absolute EtOH (10g in 150mL). Note that the rate of solution in boiling EtOH is slow (15-30minutes). It should be stored in a cool dry place, but some decomposition could occur after several weeks. [Deghenghi Org Synth Coll Vol V 645 1973.] It is very soluble in H2O and can be crystallised from Et2O. [Kfod Acta Chem Scand 10 256 1956, Beilstein 3 IV 170.]
ヒドロキシ尿素 上流と下流の製品情報
原材料
準備製品