Procarbazine

Base Information

• Chemical Name: Procarbazine
• CAS No.: 671-16-9
• Molecular Formula: C12H19 N3 O
• Molecular Weight: 221.302
• Hs Code.: 2928000090
• European Community (EC) Number: 211-582-2
• NSC Number: 759626
• UNII: 35S93Y190K
• DSSTox Substance ID: DTXSID4021189
• Nikkaji Number: J3.018J
• Wikipedia: Procarbazine
• Wikidata: Q418656
• NCI Thesaurus Code: C62072
• RXCUI: 8702
• Metabolomics Workbench ID: 43386
• ChEMBL ID: CHEMBL1321
• Mol file: 671-16-9.mol

Synonyms:Hydrochloride, Procarbazine;Matulane;Monohydrobromide, Procarbazine;Monohydrochloride, Procarbazine;Natulan;Procarbazine;Procarbazine Hydrochloride;Procarbazine Monohydrobromide;Procarbazine Monohydrochloride

Chemical Property of Procarbazine

Chemical Property:

• Refractive Index: 1.5290 (estimate)
• Boiling Point: 384.6 °C at 760 mmHg
• PKA: pKa 6.8(H2O,I=0.1) (Uncertain)
• Flash Point: 148.9 °C
• PSA: 53.16000
• Density: 1.035 g/cm³
• LogP: 2.22150
• Storage Temp.: Keep in dark place,Inert atmosphere,Store in freezer, under -20°C
• XLogP3: 0.1
• Hydrogen Bond Donor Count: 3
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 5
• Exact Mass: 221.152812238
• Heavy Atom Count: 16
• Complexity: 210

Purity/Quality:

98%,99%, ^*data from raw suppliers

PCX ^*data from reagent suppliers

Safty Information:

• Pictogram(s):  
• Hazard Codes: 

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents, Alkylating Agents
• Canonical SMILES: CC(C)NC(=O)C1=CC=C(C=C1)CNNC
• Recent ClinicalTrials: Study on Tailored Treatment in Elderly Patients With Newly Diagnosed Primary Lymphoma of Central Nervous System
• Recent EU Clinical Trials: Phase 2 Study of Pembrolizumab and Chemotherapy in Patients With Newly Diagnosed Classical Hodgkin Lymphoma (KEYNOTE-C11)
• Recent NIPH Clinical Trials: JCOG1305: Interim response adapted strategy for the advanced stage of Hodgkin Lymphoma
• Uses: antibacterial Procarbazine was initially synthesized as an MAO inhibitor. However, it was discovered later on that it has ability to act as an alkylating agent and inhibit DNA, RNA, and protein synthesis. Along with this, there is an opinion that procarbazine accumulates in cancerous tissue and generates peroxide and hydroperoxide radicals in cells, which imitates the effect of ionizing radiation. It is used for malignant tumors of lymphatic tissue, brain tumors, lung tumors, and Hodgkin’s disease. A synonym of this drug is natulan.
• Indications: Procarbazine (Matulane) may autooxidize spontaneously, and during this reaction hydrogen peroxide and hydroxyl free radicals are generated. These highly reactive products may degrade DNA and serve as one mechanism of procarbazine-induced cytotoxicity. Cell toxicity also may be the result of a transmethylation reaction that can occur between the N-methyl group of procarbazine and the N7 position of guanine. Procarbazine exhibits an interesting interaction with ethanol, resulting in headaches, diaphoresis, and facial erythema; patients taking this drug should be forewarned to abstain from alcohol. Procarbazine is also a monoamine oxidase (MAO) inhibitor and may potentiate the effects of drugs that are substrates for this enzyme.
• Clinical Use: When originally tested as a single agent in advanced Hodgkin’s disease, procarbazine produced tumor regression responses that were brief, usually lasting only 1 to 3 months. The combination of procarbazine with mechlorethamine, vincristine, and prednisone in the MOPP regimen, however, resulted in an 81% complete remission rate in Hodgkin’s disease. Most of these patients are considered cured. Procarbazine is also used in various combination chemotherapy protocols for non- Hodgkin’s lymphomas and small cell anaplastic (oat cell) carcinoma of the lung. Limited antitumor effects have been observed against multiple myeloma, melanoma, and non–oat cell lung cancers.
• Drug interactions: Potentially hazardous interactions with other drugs Alcohol: may produce a disulfiram reaction. Antipsychotics: avoid concomitant use with clozapine (increased risk of agranulocytosis).

Technology Process of Procarbazine

There total 8 articles about Procarbazine 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: 74.0%

methylhydrazine sulfuric acid (302-15-8) + 4-Formyl-benzoesaeure-isopropylamid (13255-50-0) → Procarbazine (671-16-9)

Guidance literature:

methylhydrazine sulfuric acid; 4-Formyl-benzoesaeure-isopropylamid; In ethanol; for 0.333333h;

With triethylamine; In ethanol; at 60 ℃; for 6h;

With sodium cyanoborohydride; In N,N-dimethyl-formamide; at 0 - 20 ℃;

Reference yield: 74.0%

methyl hydrazine hydrochloride (7339-53-9,55330-60-4,88216-08-4) + 4-Formyl-benzoesaeure-isopropylamid (13255-50-0) → Procarbazine (671-16-9)

Guidance literature:

methyl hydrazine hydrochloride; 4-Formyl-benzoesaeure-isopropylamid; In ethanol; for 0.333333h; Sealed tube;

With triethylamine; In ethanol; at 60 ℃; for 6h; Sealed tube;

With sodium cyanoborohydride; In N,N-dimethyl-formamide; at 0 - 20 ℃;

DOI:10.1016/j.bioorg.2018.11.011

Reference yield:

4-methyl-benzoyl chloride (874-60-2) → Procarbazine (671-16-9)

Guidance literature:

Multi-step reaction with 3 steps

1.1: dichloromethane

2.1: ammonium cerium (IV) nitrate; nitric acid / 24 h / 100 °C / Sealed tube

3.1: ethanol / 0.33 h / Sealed tube

3.2: 6 h / 60 °C / Sealed tube

3.3: 0 - 20 °C

With ammonium cerium (IV) nitrate; nitric acid; In ethanol; dichloromethane;

DOI:10.1016/j.bioorg.2018.11.011

upstream raw materials:

4-[(2-methyl-1,2-dicarbobenzoxyhydrazino)-methyl]-benzoic acid isopropylamide

methyl hydrazine hydrochloride

4-Formyl-benzoesaeure-isopropylamid

4-methyl-benzoyl chloride

Downstream raw materials:

p-formyl-N-isopropylbenzamide methylhydrazone

azoprocarbazine

4-Formyl-benzoesaeure-isopropylamid

4-(N-Methyl-N-nitroso-hydrazonomethyl)-benzoesaeureisopropylamid

Refernces

• 1、 -. "Synthesis process of anti-cancer medicine propiconazole (by machine translation)". . . Retrieved 2019/10/10.
• 2、 -. "THERAPEUTIC FOR HEPATIC CANCER". . . Retrieved 2011/02/18.