671-16-9 Usage
Uses
Different sources of media describe the Uses of 671-16-9 differently. You can refer to the following data:
1. antibacterial
2. 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.
Definition
ChEBI: A benzamide obtained by formal condensation of the carboxy group of 4-[(2-methylhydrazino)methyl]benzoic acid with the amino group of isopropylamine. An antineoplastic chemotherapy drug used for treatment of Hodgkin's lymphoma. Metabolism yields azo-procar
azine and hydrogen peroxide, which results in the breaking of DNA strands.
Indications
Different sources of media describe the Indications of 671-16-9 differently. You can refer to the following data:
1. 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.
2. 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.
Mechanism of action
Procarbazine is rapidly absorbed after oral administration
and has a plasma half-life of only 10 minutes.
The drug crosses the blood-brain barrier, reaching levels
in CSF equal to those obtained in plasma.
Metabolism is extensive and complex. Urinary excretion
accounts for 70% of the procarbazine and its
metabolites lost during the first 24 hours after drug administration.
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.
Side effects
The major side effects associated with procarbazine
therapy are nausea and vomiting, leukopenia, and thrombocytopenia.
Skin rashes have been reported, as have
rare cases of allergic interstitial pneumonia. Procarbazine
administration produces a high degree of chromosomal
breakage, and the compound is mutagenic, teratogenic,
and carcinogenic in experimental systems.
Procarbazine may potentiate the effects of tranquilizers
and hypnotics. Hypertensive episodes can result if
procarbazine is administered simultaneously with
adrenomimetic drugs or with tyramine-containing
foods. Rarely, a reaction to alcohol similar to that provoked
by disulfiram may occur.
Synthesis
Procarbazine, 1-methyl-2-(n-isopropylcarbamoylbenzyl)-hydrazine (30.6.8),
is synthesized from 1,2-bis-(benzyloxycarbonyl)-1-methylhydrazine, which is alkylated by
the methyl ester of 4-bromomethylbenzoic acid in the presence of sodium hydride, which
forms 1,2-bis(benzyloxycarbonyl)-1-methyl-2-(p-carbomethoxy)benzylhydrazine (30.6.6).
The carbomethoxy group of this molecule is hydrolyzed by sodium hydroxide, and the
resulting carboxyl group is transformed into a acid chloride group, followed by a reaction of
this product with isopropylamine gives 1,2-bis-(binzyloxycarbonyl)-1-methyl-2-(p-isopropylcarbamoyl)benzylhydrazine (30.6.7). Hydrolyzis of the benzyloxycarbonyl group in
the resulting compound with hydrogen bromide in acetic acid gives the desired procarbazine
(30.6.8).
Drug interactions
Potentially hazardous interactions with other drugs
Alcohol: may produce a disulfiram reaction.
Antipsychotics: avoid concomitant use with
clozapine (increased risk of agranulocytosis).
Carcinogenicity
Procarbazine and procarbazine hydrochloride are reasonably anticipated to be human carcinogens based on sufficient evidence of carcinogenicity from studies in experimental animals. The names “procarbazine” and “procarbazine hydrochloride” are used interchangeably in published studies; because only procarbazine hydrochloride is produced, it has been assumed that procarbazine hydrochloride was the substance under study.
Metabolism
Procarbazine is metabolised to an active alkylating agent
by microsomal enzymes in the liver and kidneys and
only about 5% is excreted unchanged in the urine. The
remainder is oxidised to N-isopropylterephthalamic
acid and excreted in the urine, with up to 70% of a dose
recovered in the urine after 24 hours.
Shipping
UN2811 Toxic solids, organic, n.o.s., Hazard
Class: 6.1; Labels: 6.1-Poisonous materials, Technical
Name Required.
Check Digit Verification of cas no
The CAS Registry Mumber 671-16-9 includes 6 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 3 digits, 6,7 and 1 respectively; the second part has 2 digits, 1 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 671-16:
(5*6)+(4*7)+(3*1)+(2*1)+(1*6)=69
69 % 10 = 9
So 671-16-9 is a valid CAS Registry Number.
InChI:InChI=1/C12H19N3O/c1-9(2)15-12(16)11-6-4-10(5-7-11)8-14-13-3/h4-7,9,13-14H,8H2,1-3H3,(H,15,16)
671-16-9Relevant articles and documents
Synthetic method of procarbazine
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Paragraph 0042; 0043; 0044, (2019/09/13)
The invention discloses a synthetic method of procarbazine (Pcb). The synthetic method comprises following steps: p-tolualdehyde is taken as an initial raw material, dibromocyanuric acid and isopropylamine are added, reaction is carried out at room temperature so as to obtain p-methyl benzoyl isopropylamine; p-methyl benzoyl isopropylamine is dissolved in an organic reagent, N-bromo-succinimide and an initiator are added, heating reflux is carried out, after reaction, the solvent is removed, acetonitrile and a hydrolysis promoter are added, heating reflux is carried out so as to obtain p-formyl benzoyl isopropylamine; p-formyl benzoyl isopropylamine and methylhydrazine sulfate are dissolved in an organic reagent, triethylamine is added for reaction, and the solvent is subjected to rotary drying, sodium cyanoborohydride is added, an obtained reaction system is heated to room temperature, reaction is carried out for more than one night so as to obtain Pcb. According to the synthetic method, bromination is carried out firstly, and then hydrolysis is carried out, p-methyl benzoyl isopropylamine is converted into p-formyl benzoyl isopropylamine, using of strong oxidizing agent and strong acid is avoided, the synthetic method is friendly to the environment, the yield is high, and the total yield of the three steps is 52.9%.
Introduction of Z-GP scaffold into procarbazine reduces spermatoxicity and myelosuppression
Wang, Rikang,Zhang, Chao,Zheng, Chaojun,Li, Huilan,Xie, Xinshu,Jin, Yi,Liu, Zhijun,Chen, Heru
, p. 461 - 467 (2018/11/24)
Incorporation of carbobenzoxy-glycylprolyl (Z-GP) to either α or β position of the hydrazine moiety in procarbazine (Pcb) has been carried on in 5-steps process. The overall yield was 32.7%. The new entity Z-GP-Pcb was confirmed targeting to fibroblast activation protein-α (FAPα). Z-GP-Pcb may be hydrolyzed by either isolated rhFAPα or tumor homogenate. It was shown far less cytotoxicity against NCI-H460 cell line than Pcb. Z-GP-Pcb was displayed the potency to reduce spermatoxcity in H22-bearing mice. The mechanism may be ascribed to the blockade of dehydrogenation by α-glycerolphosphate dehydrogenase. This candidate was further proved equal antitumor activity to Pcb. However, the introduction of Z-GP scaffold decreased myelosuppression. All the evidences support that Z-GP-Pcb is a better antitumor agent than Pcb.
Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
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, (2010/05/13)
Monoclonal antibodies that bind specifically to Claudin 3 expressed on cell surface are provided. The antibodies of the present invention are useful for diagnosis of cancers that have enhanced expression of Claudin 3, such as ovarian cancer, prostate cancer, breast cancer, uterine cancer, liver cancer, lung cancer, pancreatic cancer, stomach cancer, bladder cancer, and colon cancer. The present invention provides monoclonal antibodies showing cytotoxic effects against cells of these cancers. Methods for inducing cell injury in Claudin 3-expressing cells and methods for suppressing proliferation of Claudin 3-expressing cells by contacting Claudin 3-expressing cells with a Claudin 3-binding antibody are disclosed. The present application also discloses methods for diagnosis or treatment of cancers.
