N-METHYL-BIS(2-CHLOROETHYL)AMINE
Chlormethine
CAS: 51-75-2
Molecular Formula: C5H11Cl2N
N-METHYL-BIS(2-CHLOROETHYL)AMINE - Names and Identifiers
N-METHYL-BIS(2-CHLOROETHYL)AMINE - Physico-chemical Properties
| Molecular Formula | C5H11Cl2N |
| Molar Mass | 156.05 |
| Density | d425 1.118 |
| Melting Point | -60° |
| Boling Point | bp18 87°; bp10 75°; bp5 64°; bp2 59° |
| Vapor Density | 0.17 mm at 25°C |
| Appearance | HN-2 has a soapyodor at low concentrations and a fruity odor athigher concentrations. |
| Color | Dark liquid |
| pKa | 6.40±0.30(Predicted) |
| Refractive Index | 1.5500 (estimate) |
| Physical and Chemical Properties | An easy-to-flow liquid. Melting point -60 ℃, boiling point 86-87 ℃(1.46kPa),59 ℃(0.266kPa), relative density 1.118(25/4 ℃). Slightly soluble in water, miscible with DMF, CS2, CCI4 and other organic solvents. The product is nitrogen mustard hydrochloride, white flake crystal, melting point 119 ℃(110 ℃), soluble in water and ethanol. |
N-METHYL-BIS(2-CHLOROETHYL)AMINE - Risk and Safety
| UN IDs | 2810 |
| Hazard Class | 6.1(a) |
| Packing Group | II |
| Toxicity | LD50 oral in rabbit: 5mg/kg |
N-METHYL-BIS(2-CHLOROETHYL)AMINE - References
| NIST chemical information | information provided by: webbook.nist.gov (external link) |
| (IARC) carcinogen classification | 2A (Vol. 9, Sup 7) 1987 |
| EPA chemical substance information | information provided by: ofmpeb.epa.gov (external link) |
| antineoplastic drugs | nitrogen mustard is one of the earliest antineoplastic drugs used in clinic and has achieved outstanding curative effect, as the representative of bischloroethylamine alkylating agent, it is a highly active compound, and its derivatives still occupy a certain position in the clinical treatment of cancer in our country. After entering the body, the product hydrolyzes and releases chloride ions in the body to become free radicals, and forms highly active ethyleneimine ions through intramolecular ring formation, rapidly combine with nucleophilic groups of various organic substances (such as carboxyl, Amino, sulfhydryl groups of proteins, amino and hydroxyl groups of nucleic acids, phosphate) under neutral or weak base conditions for alkylation, affect nucleic acid metabolism, inhibit cell mitosis, has a strong cytotoxic effect, leading to cell death. The disadvantage is that the effect of tumor cells and normal cells is not different, the selectivity is poor, so the toxicity is also large. nitrogen mustard is a non-specific drug in the cell cycle. The most important reaction is covalent binding to the 7th nitrogen of guanine, cross-linking within a double strand of DNA or cross-linking of different bases within the same strand of DNA is produced. G1 phase and M phase cells were most sensitive to the cytotoxicity of nitrogen mustard, and the G1 phase was delayed into S phase. Large doses of each cycle of cells and non-proliferating cells have killing effect. The aqueous solution of the drug is extremely unstable and dissociates quickly after entering the body. 90% of the drug in plasma disappears within 0.5~1 minute, so the effect is short-lived. But its effect can last for a long time. In the body of the distribution of no obvious selectivity, but less distribution in the brain, a very small amount of the original form from the urine. In addition, this product has a weak immunosuppressive effect. There are many known alkylating agents such as nitrogen mustard (enbixing), chlorambucil (oxycodone) and cyclophosphamide, but cyclophosphamide is more commonly used. It has been reported that cyclophosphamide acts on B cells to show an inhibitory effect on antibody production; Animal tests have shown that it is also effective for ongoing immune responses and the formation of antigen-antibody complexes. In clinic, can also be used for type II, Type IV and other allergic reactions. Cyclophosphamide can be synthesized from BIS (2-chloroethyl) phosphoramide and propanolamine. |
| pharmacokinetics | nitrogen mustard quickly binds to water or certain components of cells after entering the blood, the residence time in the blood is only 0.5~1 minutes, that is, more than 90% is eliminated from the blood, and it is rapidly distributed in the lung, small intestine, spleen, kidney, liver and muscle and other tissues, and the content in the brain is the least. The half-life of nitrogen mustard is very short. It is proved from the dog test that the blood drug concentration is reduced by 65% ~ 90% within 48 hours, the urinary excretion of the prototype was less than 0.01. After administration of 6 hours and 24 hours in the blood and tissue content is very low, 20% of the drug in the form of carbon dioxide by the respiratory tract, there are a variety of metabolites from the urine. |
| indications | for the treatment of malignant lymphomas, including Hodgkin's disease, lymphosarcoma, reticulocytic sarcoma, macrofollicular lymphoma, mycosis fungoides, and lung cancer, especially for undifferentiated carcinoma has better curative effect. If combined use of drugs, the effect is better, especially MOPP regimen (ie, combined use of nitrogen mustard, vincristine, methyl benzyl hydrazine and prednisone) in the treatment of Hodgkin's disease, the effective rate can reach more than 80%. It is also effective for lung cancer, chronic myelogenous leukemia, chronic lymphocytic leukemia, head and neck cancer, breast cancer, ovarian cancer, choriocarcinoma and the like. Due to the rapid action of nitrogen mustard, it is often combined with radiotherapy, so that the serious complications such as superior vena cava syndrome and spinal cord compression can be quickly alleviated. Intracavitary injection can treat malignant body cavity effusion. Local use of its ethanol or dimethyl sulfoxide (0.05) solution in the treatment of psoriasis, vitiligo, mycosis fungoides, but also has a good short-term effect. It can also be used as an immunosuppressive agent. |
| usage and dosage | because nitrogen mustard has obvious local irritation, it is usually only given intravenously, intracavitary injection may be performed if necessary. intravenous infusion: 0.1mg/kg each time, usually 4~5mg each time, a dose of not more than 8mg, with sterilized saline 10ml dissolved, slow infusion from 5% Dextrose Injection infusion tube. After the infusion, the infusion was continued for several minutes to continuously dilute the concentration of nitrogen mustard and reduce the local irritation to blood vessels. Start 3 times a week, can be changed to 2 times a week, the total amount of 30~50mg, generally 4~6 times for a course of treatment. intracavitary injection: according to the amount of effusion and the patient's reaction, the chest, abdominal cavity, 5~10mg each time, pericardial cavity, about 5mg each time, with 10ml sterile saline solution, after pumping fluid into the cavity. After the injection, the patient was instructed to change the position several times so that the liquid was evenly distributed in the cavity. Every 5~7 days 1 times, 4~5 times for a course of treatment. |
| adverse reactions | This product has large toxicity and severe local reactions. Blood system: the most common adverse reactions were myelosuppression, white blood cell and platelet count decreased significantly, and in severe cases, pancytopenia could be reduced, and recovery could be started 2 to 3 weeks after drug withdrawal. digestive system: mainly Nausea, Vomit and anorexia. It usually occurs 3 to 6 hours after injection, Nausea can disappear within 8 hours, Vomit and anorexia can last 24 hours. Antiemetics and sedatives should be administered before use. genitourinary system: Menstrual disorder, ovarian failure, testicular atrophy, decreased sperm, etc. Local tissue: Local stimulation is strong, multiple injections can cause vascular sclerosis, pain and thrombophlebitis. High concentration of local perfusion can lead to severe peripheral phlebitis, muscle necrosis and peeling. Such as fluid leakage can cause local tissue necrosis. carcinogenesis: Long-term use of drugs, the risk of secondary tumors increased. nervous system and other: nitrogen mustard can also cause dizziness, Fatigue and hair loss, local administration can produce delayed skin allergic reaction. Large doses can cause hypocalcemia and heart damage, dose more than 0.6mg/kg can cause adverse reactions of the central nervous system. |
| precautions | during the medication, the hemogram should be strictly checked, and the white blood cells and platelets should be checked regularly (1~2 times a week). If the white blood cell is less than 3.5 × 109/L or the platelet is less than 8 × 1010/L, the drug should be discontinued. Previous radiotherapy, chemotherapy or associated with other bone marrow dysfunction patients should be used with caution or reduction. 1. Allergic to this product, pregnant women and lactating women disabled. 2. Patients with bone marrow suppression, patients with infection, patients with tumor cell infiltration into the bone marrow, and patients who have received multiple cycles of chemotherapy or radiotherapy should be used with caution. 3. Nausea, Vomit or Diarrhea, anorexia often occur 3 to 6 hours after injection, and can last for 24 hours. Antiemetics should be added before use of nitrogen mustard. 4. Can cause reproductive system dysfunction, including menstrual disorders, testicular atrophy, sperm reduction and so on. 5. The stimulation of local tissue is strong, multiple injections can cause vascular sclerosis, pain and thrombophlebitis, such as drug spillover can cause local tissue necrosis. 6. When the static pulse is in, the needle should first be checked whether it is still in the blood vessel (see if there is blood return), and the leakage of the drug solution from the blood vessel should be prevented, once leakage should be immediately with 0.25 sodium thiosulfate injection or 1% procaine injection local injection, and cold for 6 to 12 hours. |
| Use | nitrogen mustard hydrochloride (C5H11CI2N. HCI,[55-86-7]) is an anti-malignant tumor drug. The product directly binds to DNA, affects its structure and function, has strong cytotoxic effect, poor selectivity, and has similar effect on proliferating cells and non-proliferating cells. Mainly used for malignant lymphoma and mycosis fungoides and lung cancer, undifferentiated cancer curative effect is good and fast, and VCR, methyl benzyl hydrazine and other combined treatment of Hodgkin's disease has a higher curative effect. For ovarian cancer, breast cancer, choriocarcinoma, prostate cancer, spermatogonial cell carcinoma and nasopharyngeal carcinoma (half body chemotherapy) also has certain curative effect. It can also be used as a mutagen in plant breeding. Nitrogen mustard hydrochloride has a strong stimulating effect on the mucosa. |
| production method | from diethanolamine by formic acid, formaldehyde methylation, thionyl chloride chloride derived. |
| category | toxic substances |
| toxicity grade | highly toxic |
| Acute toxicity | oral-rat LD50: 10 mg/kg; Oral-mouse LD50: 10 mg/kg |
| stimulation data | eyes -0.4 mg severe in rabbits; eye-rabbit 0.02 mg/30 min moderate |
| flammability hazard characteristics | flammable; Toxic NOx and chloride fumes from combustion; blisters and erosions from skin contact |
| storage and transportation characteristics | The warehouse is ventilated and dried at low temperature; Stored separately from food raw materials |
| fire extinguishing agent | dry powder, foam, sand, carbon dioxide, water mist |
| toxic substance data | information provided by: pubchem.ncbi.nlm.nih.gov (external link) |
Last Update：2024-04-09 02:00:23
