Carmustine

Base Information

• Chemical Name: Carmustine
• CAS No.: 154-93-8
• Deprecated CAS: 1159711-15-5,1191292-23-5
• Molecular Formula: C5H9Cl2N3O2
• Molecular Weight: 214.051
• Hs Code.: 29241990
• European Community (EC) Number: 205-838-2
• NSC Number: 758392,409962
• UN Number: 2811
• UNII: U68WG3173Y
• DSSTox Substance ID: DTXSID8022743
• Nikkaji Number: J2.968H
• Wikipedia: Carmustine
• Wikidata: Q415869
• NCI Thesaurus Code: C349
• RXCUI: 2105
• Pharos Ligand ID: BDR6KT81M7WL
• Metabolomics Workbench ID: 42658
• ChEMBL ID: CHEMBL513
• Mol file: 154-93-8.mol

Synonyms:1,3-Bis(2-Chloroethyl)-1-Nitrosourea;BCNU;BiCNU;Carmustine;FIVB;N,N'-Bis(2-Chloroethyl)-N-Nitrosourea;Nitrumon

Chemical Property of Carmustine

Chemical Property:

• Appearance/Colour: light yellow powder
• Melting Point: 30 °C(lit.)
• Refractive Index: 1.548
• Boiling Point: 404oC
• PKA: 10.19±0.46(Predicted)
• PSA: 61.77000
• Density: 1.46 g/cm³
• LogP: 1.54790
• Storage Temp.: −20°C
• Solubility.: insoluble in H2O; ≥21.51 mg/mL in DMSO; ≥27.15 mg/mL in EtOH
• Water Solubility.: <0.1 g/100 mL at 18℃
• XLogP3: 1.5
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 4
• Exact Mass: 213.0071819
• Heavy Atom Count: 12
• Complexity: 156
• Transport DOT Label: Poison

Purity/Quality:

96% up, ^*data from raw suppliers

Carmustine ^*data from reagent suppliers

Safty Information:

• Pictogram(s): T+
• Hazard Codes: T+
• Statements: 45-46-60-61-28
• Safety Statements: 53-22-36/37/39-45

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents, Alkylating Agents
• Canonical SMILES: C(CCl)NC(=O)N(CCCl)N=O
• Recent ClinicalTrials: New Combination of Chemoimmunotherapy for Systemic B-cell Lymphoma With Central Nervous System Involvement
• Recent EU Clinical Trials: Optimizing MATRix as remission induction in PCNSL:
• Recent NIPH Clinical Trials: JCOG1703: A multicenter randomized phase III study for newly-diagnosed maximally resected glioblastoma comparing Carmustine wafer implantation followed by chemoradiotherapy with temozolomide with chemoradiotherapy alone
• Uses: The product is a broad-spectrum anti-cancer drug with excellent efficacy for the treatment of acute leukemia and Hodgkin's disease as well certain efficacy on the treatment of breast cancer, lung cancer and brain cancer as well as the bone metastases of cancer as well. Oral administration for mouse has a LD50 of 19-25mg/kg while the value for intraperitoneal injection is 26mg/kg, 24 mg/kg for subcutaneous injection; rat which is subject to oral administration has a LD50 of 30-40mg/kg. BCNU has been used since 1971 as an anticancer drug and in 1977 was approved by the U.S. Food and Drug Administration, as carmustine, to be marketed for the treatment of Hodgkin’s disease, nonHodgkin’s lymphoma, multiple myeloma, and primary or metastatic brain tumors (IARC 1981, FDA 2009a, MedlinePlus 2009). It has also been used to treat malignant melanoma, breast cancer, gastrointestinal cancer, Ewing’s sarcoma, and Burkitt’s lymphoma and to be applied to the skin to treat mycosis fungoides (MedlinePlus 2009). BCNU may be used alone or in combination with other antineoplastic agents (ClinicalTrials 2009). 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 antidepressant Carmustine is a nitrogen mustard β-chloro-nitrosourea compound that is used as an alkylating agent. It forms interstrand crosslinks in DNA, which prevents DNA replication and transcription leading to apoptosis. Carmustine is also reported to inhibit glutathione reductase, thioredoxin reductase, and lipoamide dehydrogenase. Carmustine has been tested in clinical trials as a cytostatic agent for Hodgkin’s and non-Hodgkin’s lymphoma, myeloma, malignant melanoma, glioblastoma, and other brain tumors.
• Production method: The product has three synthetic routes: 1. take ethylene imine as raw material, go through phosgene condensation to generate bis-(β-chloroethyl) urea, and then generate carmustin via nitrosation; 2.take urea as raw material, go through condensation, ring-opening, chlorination, nitrosation to obtain it; 3.take ethanolamine as raw materials, and generate carmustin through similar processes as methods2. The first method can generate the finished product with just two steps but with its raw material, phosgene and ethyleneimine, both being extremely toxic chemicals, therefore demanding a high-level labor protection and production equipment. The second method has readily available raw materials as well as convenient operation.
• Description: Bischloroethyl nitrosourea (BCNU) is a mustard-gas-derived alkylating agent that underwent clinical trials for use as an antineoplastic agent in the mid-1960s. Intravenous BCNU received US Food and Drug Administration (FDA) approval for brain tumor treatments in 1977. Further development and trials led to the FDA approval of a BCNU-impregnated polymer wafer for use as an intracavity surgical adjunct for recurrent glioblastoma moltiforme in 1996. These wafers were again reapproved in 2003 for use in high-grade malignant glioma as an adjunct to surgery and radiation. Carmustine is a nitrogen mustard β-chloro-nitrosourea compound that is used as an alkylating agent. It forms interstrand crosslinks in DNA, which prevents DNA replication and transcription leading to apoptosis. Carmustine is also reported to inhibit glutathione reductase, thioredoxin reductase, and lipoamide dehydrogenase. Carmustine has been tested in clinical trials as a cytostatic agent for Hodgkin’s and non-Hodgkin’s lymphoma, myeloma, malignant melanoma, glioblastoma, and other brain tumors.
• Therapeutic Function: Antitumor
• Clinical Use: Alkylating agent: Myeloma, lymphoma and brain tumours
• Drug interactions: Potentially hazardous interactions with other drugs Antipsychotics: avoid with clozapine (increased risk of agranulocytosis).

Technology Process of Carmustine

There total 3 articles about Carmustine 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: 100.0%

1,3-bis(2-chloroethyl)urea (2214-72-4) → 1,3-bis(2-chloroethyl)-1-nitrosourea (154-93-8)

Guidance literature:

With tin(IV) chloride; sodium nitrite; In dichloromethane; at 20 ℃; for 2h;

DOI:10.1055/s-2006-942397

Reference yield:

1,2,2,2-Tetrachloroethyl N-(2-chloroethyl) N-nitroso-carbamate (113900-20-2) + chloroethylamine (689-98-5) → 1,3-bis(2-chloroethyl)-1-nitrosourea (154-93-8)

Guidance literature:

With potassium carbonate; In tetrahydrofuran; for 2h; Yield given; Ambient temperature;

DOI:10.1055/s-1987-28160

Reference yield:

→ 1,3-bis(2-chloroethyl)-1-nitrosourea (154-93-8)

Guidance literature:

upstream raw materials:

1,3-bis(2-chloroethyl)urea

1,2,2,2-Tetrachloroethyl N-(2-chloroethyl) N-nitroso-carbamate

chloroethylamine

Downstream raw materials:

1,3-bis(2-chloroethyl)urea

2-<(2-chloroethyl)amino>-2-oxazoline

1-(2-chloroethyl)imidazolidin-2-one

ethanol

Refernces

• 1、 -. "SAFE AND EFFICIENT PROCESS FOR THE PREPARATION OF CARMUSTINE". Paragraph 0074-0077. . Retrieved 2017/09/25.
• 2、 -. "PROCESS FOR PREPARATION OF CARMUSTINE". Page/Page column 9. . Retrieved 2017/11/10.