3-(2-chloroethyl)-1-cyclohexyl-3-nitrosourea

• ChemBase ID: 1076
• Molecular Formular: C9H16ClN3O2
• Molecular Mass: 233.69524
• Monoisotopic Mass: 233.09310445
• SMILES: ClCCN(N=O)C(=O)NC1CCCCC1
• Canonical SMILES: ClCCN(C(=O)NC1CCCCC1)N=O
• InChI: InChI=1S/C9H16ClN3O2/c10-6-7-13(12-15)9(14)11-8-4-2-1-3-5-8/h8H,1-7H2,(H,11,14)
• InChIKey: GQYIWUVLTXOXAJ-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 3-(2-chloroethyl)-1-cyclohexyl-3-nitrosourea
• IUPAC Traditional name: lomustine
• Brand Name: Belustine; CINU; Cecenu; CeeNU
• Synonyms: N-(2-Chloroethyl)-N'-cyclohexyl-N-nitrosourea; 1-(2-Chloroethyl)-1-nitroso-3-cyclohexylurea; Belustine; Cecenu; CeeNU; CiNu; NSC 79037; Chloroethylcyclohexylnitrosourea; Lomustina [INN-Spanish]; Lomustinum [INN-Latin]; CCNU; Lomustine; CeeNU; 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea; Lomustine; 1-(2-Chloroethyl)-3-cyclohexyl-1-nitrosourea; Lomustine

Database IDs

• CAS Number: 13010-47-4
• EC Number: 235-859-2
• MDL Number: MFCD00012392
• PubChem SID: 160964539; 46506562
• PubChem CID: 3950

CALCULATED PROPERTIES

JChem

• Acid pKa: 13.3029785
• H Acceptors: 2
• H Donor: 1
• LogD (pH = 5.5): 2.1574368
• LogD (pH = 7.4): 2.1574364
• Log P: 2.157437
• Molar Refractivity: 58.6506 cm^3
• Polarizability: 21.922037 Å^3
• Polar Surface Area: 61.77 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: 2.62
• LOG S: -2.49
• Solubility (Water): 7.55e-01 g/l

PROPERTIES

Physical Property

• Solubility: 111 mg/L; Acetone; Chloroform; Ethanol; Water
• Apperance: Yellow Powder
• Melting Point: 88-90°C; 90°C
• Hydrophobicity(logP): 3

Safety Information

• Storage Condition: -20°C
• Storage Warning: IRRITANT
• RTECS: YS4900000
• European Hazard Symbols: Toxic (T)
• UN Number: 2811
• German water hazard class: 3
• Hazard Class: 6.1
• Packing Group: 3
• Risk Statements: 45-25
• Safety Statements: 53-45
• TSCA Listed: false
• GHS Pictograms: GHS06; GHS08
• GHS Signal Word: Danger
• GHS Hazard statements: H301-H350
• GHS Precautionary statements: P201-P301 + P310-P308 + P313
• Personal Protective Equipment: 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 3
• Storage Temperature: -20°C

Product Information

• Purity: ≥98%; 95+%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C9H16ClN3O2

DETAILS

DrugBank - DB01206

• Drug Groups: approved
• Description: An alkylating agent of value against both hematologic malignancies and solid tumors. [PubChem]
• Indication: For the treatment of primary and metastatic brain tumors as a component of combination chemotherapy in addition to appropriate surgical and/or radiotherapeutic procedures. Also used in combination with other agents as secondary therapy for the treatment of refractory or relapsed Hodgkin's disease.
• Pharmacology: Lomustine is an alkylating agent of the nitrosourea type. Lomustine and its metabolites interferes with the function of DNA and RNA. It is cell cycle–phase nonspecific. Cancers form when some cells within the body multiply uncontrollably and abnormally. These cells then spread and destroy nearby tissues. Lomustine acts by slowing this process down. It kills cancer cells by damaging the DNA (the genetic material inside the cells) and stops them from dividing.
• Toxicity: Oral, rat: LD₅₀ = 70 mg/kg. Pulmonary toxicity has been reported at cumulative doses usually greater than 1,100 mg/m2. There is one report of pulmonary toxicity at a cumulative dose of only 600 mg. The onset of toxicity has varied from 6 months after initiation of therapy, to as late as 15 years after.
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic. Rapid and complete, with active metabolites.
• Absorption: Well and rapidly absorbed from the gastrointestinal tract.
• Half Life: Approximately 94 minutes, however the metabolites have a serum half-life of 16 to 48 hours.
• Protein Binding: 50%
• Elimination: Following oral administration of radioactive CeeNU at doses ranging from 30 mg/m2 to 100 mg/m2, about half of the radioactivity given was excreted in the urine in the form of degradation products within 24 hours.
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1840

Research Area: Cancer
Biological Activity:
Lomustine (CeeNU) is an alkylating agent of value against both hematologic malignancies and solid tumors. Lomustine is a highly lipophilic nitrosourea compound which undergoes hydrolysis in vivo to form reactive metabolites. These metabolites cause alkylation and cross-linking of DNA. Other biologic effects include inhibition of DNA synthesis and some cell cycle phase specificity. Nitrosureas generally lack cross-resistance with other alkylating agents. [1]

Sigma Aldrich - L5918

Biochem/physiol Actions
Antineoplastic agent with cellular DNA effects.1,2,3 Lomustine induces p53 expression in A2870 cells.4

Toronto Research Chemicals - L469440

Chloroethylnitrosourea derivative with antitumor activity. Similar to carmustine, chlorozotocin, nimustine, ranimustine. Antineoplastic.

REFERENCES

• http://www.drugbank.ca/drugs/DB01206
• Johnston, T.P., et al.: J. Med. Chem., 9, 892 (1966)
• Oliverio, V.T., et al.: Cancer Res., 30, 1330 (1966)
• Thompson, G.R., et al.: Toxicol. Appl. Pharmacol., 21, 405 (1966)
• Al-Shammary, F.J., et al.: Anal. Profiles Drug Subs., 19, 315 (1966)