1,3-bis(2-chloroethyl)-1-nitrosourea

• ChemBase编号: 147
• 分子式: C5H9Cl2N3O2
• 平均质量: 214.04986
• 单一同位素质量: 213.0071819
• SMILES: ClCCN(N=O)C(=O)NCCCl
• Canonical SMILES: ClCCNC(=O)N(CCCl)N=O
• InChI: InChI=1S/C5H9Cl2N3O2/c6-1-3-8-5(11)10(9-12)4-2-7/h1-4H2,(H,8,11)
• InChIKey: DLGOEMSEDOSKAD-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: 1,3-bis(2-chloroethyl)-1-nitrosourea; 1,3-bis(2-chloroethyl)-3-nitrosourea
• IUPAC传统名: 1,3-bis(2-chloroethyl)-1-nitrosourea; carmustine
• 商标名: Becenun; Bi CNU; Carmubris; Gliadel; Gliadel Wafer; Nitrumon; BiCNU
• 别名: BCNU, N,N’-Bis(2-chloroethyl)-N-nitrosourea, NSC-409962, Becenun, Bicnu,; BCNU; Bischlorethylnitrosourea; Bischlorethylnitrosurea; Carmustin; Carmustine; 1,3-Bis(2-chloroethyl)-1-nitrosourea; Carmustine; Becenum; Carmubris; Nitrumon

登记号

• CAS号: 154-93-8
• EC号: 205-838-2
• MDL号: MFCD00057706
• PubChem SID: 24278289; 46506980; 160963610
• PubChem CID: 2578

理论计算性质

JChem

• Acid pKa: 11.963143
• 质子受体: 2
• 质子供体: 1
• LogD (pH = 5.5): 1.0226562
• LogD (pH = 7.4): 1.0226457
• Log P: 1.0226563
• 摩尔折射率: 46.9797 cm^3
• 极化性: 17.322094 Å^3
• 极化表面积: 61.77 Å^2
• 可自由旋转的化学键: 5
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: 1.24
• LOG S: -2.15
• 溶解度: 1.53e+00 g/l

分子性质

理化性质

• 溶解度: < 0.1 g/100 mL at 18 °C; DMSO; Methanol
• 外观: (Oily liquid to amorphous solid); Light Yellow to Pale Orange Solid
• 熔点: 30 °C(lit.); 30-32°C
• 疏水性(logP): 1.5

安全信息

• 保存条件: -20°C Freezer
• RTECS编号: YS2625000
• 欧盟危险性物质标志: 剧毒(Highly toxic) (T+)
• 联合国危险货物编号: 2811
• 德国WGK号: 3
• 联合国危险货物等级: 6.1
• 联合国危险货物包装类别(PG): 2
• 危险公开号: 45-46-60-61-28
• 安全公开号: 53-22-36/37/39-45
• GHS危险品标识: GHS06; GHS08
• GHS警示词: Danger
• GHS危险声明: H300-H350-H360
• GHS警示性声明: P201-P264-P301 + P310-P308 + P313
• 个人保护装置: Eyeshields, Faceshields, full-face particle respirator type N100 (US), Gloves, respirator cartridge type N100 (US), type P1 (EN143) respirator filter, type P3 (EN 143) respirator cartridges
• RID/ADR: UN 2811 6.1/PG 2
• 保存温度: -20°C

药理学性质

• 相关基因信息: human ... GSR(2936)
• 生物活性机理: Alkylating agent in cancer chemotherapy

产品相关信息

• 纯度: ≥98%
• 应用领域: Antineoplastic agent; Used to treat gliomas, glioblastoma multiforme, medulloblastoma and astrocytoma, multiple myeloma and lymphoma (Hodgkin's and non-Hodgkin).
• Empirical Formula (Hill Notation): C5H9Cl2N3O2

详细说明

DrugBank - DB00262

• Drug Groups: approved
• Description: A cell-cycle phase nonspecific alkylating antineoplastic agent. It is used in the treatment of brain tumors and various other malignant neoplasms. (From Martindale, The Extra Pharmacopoeia, 30th ed, p462) This substance may reasonably be anticipated to be a carcinogen according to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985). (From Merck Index, 11th ed)
• Indication: For the treatment of brain tumors, multiple myeloma, Hodgkin's disease and Non-Hodgkin's lymphomas.
• Pharmacology: Carmustine is one of the nitrosoureas indicated as palliative therapy as a single agent or in established combination therapy with other approved chemotherapeutic agents in treatment of brain tumors, multiple myeloma, Hodgkin's disease, and non-Hodgkin's lymphomas. Although it is generally agreed that carmustine alkylates DNA and RNA, it is not cross resistant with other alkylators. As with other nitrosoureas, it may also inhibit several key enzymatic processes by carbamoylation of amino acids in proteins.
• Toxicity: The oral LD₅₀s in rat and mouse are 20 mg/kg and 45 mg/kg, respectively. Side effects include leukopenia, thrombocytopenia, nausea. Toxic effects include pulmonary fibrosis (20-0%) and bone marrow toxicity.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic and rapid with active metabolites. Metabolites may persist in the plasma for several days.
• Absorption: 5 to 28% bioavailability
• Half Life: 15-30 minutes
• Protein Binding: 80%
• Elimination: Approximately 60% to 70% of a total dose is excreted in the urine in 96 hours and about 10% as respiratory CO2.
• External Links: Wikipedia; RxList; Drugs.com

Sigma Aldrich - C0400

Biochem/physiol Actions
Carmustine is a DNA alkylating agent causing DNA interstrand crosslinks.1 Effective against glioma and other solid tumors.

Toronto Research Chemicals - C183875

An alkylating and carbamoylating nitrosourea compound. It interacts with DNA, RNA and proteins causing DNA interstrand cross linking which is cytotoxic and leads to apoptotic cell death.

参考文献

• 10764 (1992)
• Stahl, et al.: Chem. Res. Toxicol., 5, 106 (1992)
• Kokkinakis, D.M., et al.: Clin. Cancer Res., 5(1992)
• 3676 (1992)
• Hickman, M.J., et al.: Proc. Natl. Acad. Sci. USA, 96(1992)
• Johnston, T.P. et al., J. Med. Chem., 1963, 6, 669, (synth)
• Loo, T.L. et al., J. Pharm. Sci., 1966, 55, 492, (pharmacol)
• Lien, E.J. et al., Spectrosc. Lett., 1972, 5, 293, (pmr)
• Thompson, G.R. et al., Toxicol. Appl. Pharmacol., 1972, 21, 405, (tox)
• Gombar, C.T. et al., Diss. Abstr. Int., B, 1980, 40, 5223; 5686, (props)
• IARC Monog., 1981, 26, 79; Suppl. 6, 116; Suppl. 7, 150, (rev, tox)
• Lown, J.W. et al., J.O.C., 1981, 46, 5309, (synth, cmr, N-15 nmr)
• Paoletti, R. et al., Am. J. Cardiol., 1983, 52, 21, (rev)
• Reed, D.J. et al., Anticancer Drugs: Reactive Metabolism and Drug Interactions, (Ed. Powis, G.) Pergamon Press, 1994, 187, (rev)
• Wiencke, J.K. et al., Mutat. Res., 1995, 339, 91, (rev, genotox)
• Martindale, The Extra Pharmacopoeia, 31st edn., Pharmaceutical Press, 1996, 550
• Kaba, S.E. et al., Drugs, 1997, 53, 235, (use, rev)
• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, BIF750