Hydroxyurea

Base Information

• Chemical Name: Hydroxyurea
• CAS No.: 127-07-1
• Molecular Formula: CH4N2O2
• Molecular Weight: 76.055
• Hs Code.: 29242100
• European Community (EC) Number: 204-821-7,232-439-0
• NSC Number: 757072,32065
• UN Number: 2811
• UNII: X6Q56QN5QC
• DSSTox Substance ID: DTXSID6025438
• Nikkaji Number: J2.937H
• Wikipedia: Hydroxycarbamide
• Wikidata: Q212272
• NCI Thesaurus Code: C560
• RXCUI: 5552
• Pharos Ligand ID: YS9WPYDSAP5A
• Metabolomics Workbench ID: 43251
• ChEMBL ID: CHEMBL467
• Mol file: 127-07-1.mol

Synonyms:Urea,hydroxy- (6CI,8CI,9CI);Biosupressin;Carbamohydroxamic acid;Carbamohydroximicacid;Carbamoyl oxime;Droxia;Hydrea;Hydreia;Hydroxycarbamide;Hydroxylamine, N-(aminocarbonyl)-;Hydura;Hydurea;Onco-Carbide;Oxyrea;Oxyurea;

Chemical Property of Hydroxyurea

Chemical Property:

• Appearance/Colour: off-white crystalline solid
• Melting Point: 135-140 °C
• Refractive Index: 1.543
• Boiling Point: 136.04°C (rough estimate)
• PKA: 10.56±0.23(Predicted)
• PSA: 75.35000
• Density: 1.457 g/cm³
• LogP: 0.13510
• Storage Temp.: 2-8°C
• Solubility.: H2O: 50 mg/mL
• Water Solubility.: soluble
• XLogP3: -1.8
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 76.027277375
• Heavy Atom Count: 5
• Complexity: 42.9
• Transport DOT Label: Poison

Purity/Quality:

99.9% ^*data from raw suppliers

Hydroxyurea ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T,Xn
• Hazard Codes: T,Xn
• Statements: 46-63-61-40
• Safety Statements: 53-36/37-45-36-22

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents; Sickle Cell Disease Agents
• Canonical SMILES: C(=O)(N)NO
• Recent ClinicalTrials: Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa
• Recent EU Clinical Trials: A multicentre trial evaluating the efficacy and safety of oral decitabine-tetrahydrouridine (NDec) in patients with sickle cell disease
• Recent NIPH Clinical Trials: Phase 2 study of pretreatment with hydroxyurea prior to induction therapy for patients with newly diagnosed acute myeloid leukemia (PREFACE study)
• Uses: It belongs to anti-metabolic anti-cancer drugs with its major role in the proliferation of cells in G1 and S phase. It also had delayed effect on G1/S interface. It is a cell-specific drug. It can be applied to biochemical studies. Through the formation of free nitric oxide, it binds to the tyrosine of the enzyme active site, leaving the nucleoside reductase inactivated. This hampers the synthesis of deoxynucleotide. It is clinically used for the treatment of chronic myelogenous leukemia as well as being used to treat metastatic ovarian cancer, head and neck primary squamous cell carcinoma and intractable psoriasis. The good belongs to anticancer drugs. Hydroxyurea USP is used to treat Chronic granulocytic leukemia; melanoma; cancer of ovary, head, neck. 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. antineoplastic, inhibits ribonucleoside diphosphate reductase
• Production method: It is produced through the reaction between ethyl carbamate and hydroxylamine hydrochloride. The sodium hydroxide solution was cooled to 20-25 ℃. Add alternately under stirring of urethane and hydroxylamine hydrochloride and react at 25-28 ℃ for 16h. Use hydrochloric acid to neutralize to a pH of 6.5-7, control the temperature be not exceeding 25 ℃. Then apply concentration under reduced pressure, filtered hot and the filtrate was cooled to below 0 ℃ to precipitate our the crystal, filter, wash crystal with ice water, and dry to give crude hydroxyurea with the yield of about 65%. After refining, we can obtain pharmaceutical grade hydroxyurea.
• Description: Readily oxidized in vivo to free radical forms, which destroy the stable tyrosyl free radical of the metalloenzyme ribonucleotide reductase, suppressing deoxyribonucleotide production and blocking DNA synthesis and repair.1,2 Reduces cell proliferation, and causes S-phase arrest and death.3 Induces p53-dependent NF-κB target gene expression in U2OS cells expressing HA-RelA.4 Stimulates fetal hemoglobin production in vitro and in vivo.5 Allows for S phase enrichment of CHO cells with maintenance of viability for enhanced site-specific genome engineering.6 Anticancer and antiviral agent.
• Indications: 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.
• Therapeutic Function: Cancer chemotherapy
• Clinical Use: 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.
• Drug interactions: Potentially hazardous interactions with other drugs Antipsychotics: avoid with clozapine, increased risk of agranulocytosis. Antivirals: increased toxicity with didanosine and stavudine - avoid. Vaccines: risk of generalised infections - avoid.

Technology Process of Hydroxyurea

There total 34 articles about Hydroxyurea which guide to synthetic route it. The literature collected by LookChem mainly comes from the sharing of users and the free literature resources found by Internet computing technology. We keep the original model of the professional version of literature to make it easier and faster for users to retrieve and use. At the same time, we analyze and calculate the most feasible synthesis route with the highest yield for your reference as below:

synthetic route:

Reference yield: 96.0%

N-(trimethylsiloxy)-N,N'-bis(trimethylsilyl)urea (126669-78-1) → N-hydroxyurea (127-07-1)

Guidance literature:

With ethanol;

Reference yield: 94.0%

N-(trimethylsiloxy)-N'-(trimethylsilyl)urea (126669-76-9) → N-hydroxyurea (127-07-1)

Guidance literature:

With ethanol; at 20 ℃; for 15h;

Reference yield: 78.0%

trimethylsilyl isocyanate (1118-02-1) + 4-(1-phenylethoxy)-2-hydroxyacetophenone → N-hydroxy-N-[1-(4-(1-phenylethoxy)-2-hydroxyphenyl)-ethyl]urea + N-hydroxyurea (127-07-1)

Guidance literature:

With pyridine; hydrogenchloride; hydroxylamine hydrochloride; hydroxylamine; In tetrahydrofuran; ethanol; dichloromethane; water; toluene;

upstream raw materials:

cyanic acid

potassium cyanate

urea

urethane

Downstream raw materials:

N-(benzoyloxy)benzamide

N-benzoyloxyurea

(4S)-4-(3-amino-isoxazol-5-yl)-O³-benzyl-O¹,O²-isopropylidene-β-L-threofuranose

4,7-dihydro-7-methyl-5-phenyl-1,2,4-oxadiazepin-3(2H)-one

Refernces

• 1、 -. "Preparing method for hydroxyurea". Paragraph 0036-0039. . Retrieved 2017/01/12.
• 2、 -. "THERAPEUTIC FOR HEPATIC CANCER". . . Retrieved 2011/02/18.