53-19-0 Usage
Uses
Used in Pharmaceutical Industry:
Mitotane is used as an antineoplastic agent for the treatment of adrenal cortical carcinoma, Cushing's Syndrome, and other adrenocortical disorders. It acts as an adrenolytic agent, suppressing cortisol synthesis and exhibiting anti-neoplastic actions, either alone or in combination with other compounds.
Used in Insecticide Industry:
Mitotane is used as an insecticide due to its toxic properties, which can help control and eliminate insect populations.
Used in Medical Treatment:
Mitotane is used as a treatment for osteoporosis and Paget's bone disease, as it can help regulate the balance of bone formation and resorption.
Used in Antineoplastic Applications:
Mitotane is used in antineoplastic applications to suppress the growth of adrenocortical cells and disrupt mitochondrial respiratory chain activity, making it effective against adrenocortical carcinoma and Cushing's Syndrome in clinical trials.
Pharmacological effects
Mitotan is structurally similar with insecticide DDT and DDD and can selectively cause the atrophy and necrosis of adrenal cortex-zona fasciculata and reticularis cells but without affecting the zona, therefore the secretion of aldosterone will not affected. After the drug administration, the cortisol and its metabolites level in blood and urine decreased rapidly after treatment. At the same time, the in vivo adrenocorticotropic hormone and metabolite products level also decrease rapidly. It is suitable for the treatment of inoperable, functional and non-functional adrenal cortical carcinoma, adrenal tumor, adrenal hyperplasia-caused Klinefelter’s syndrome, adrenal hyperplasia, and the adjuvant therapy of postoperation cortical cancer and tumor-induced Cushing's syndrome.
After oral administration, about 40% of Mitotan is absorbed through the gastrointestinal tract with the remaining 60% of the prototype excreted together with the feces. At a dose of 5~10 g daily, the plasma concentration can be up to 10~90μg/ml, the concentration of metabolites can be up to 30~50μg/ml. At 6-9 weeks after discontinuation, it can be still detected of o-alkyl chloride in the plasma. Mitotan has a high fat-solubility and is mainly stored in fat. The water soluble metabolites discharged from the urine can account for about 25% of the administered dose.
The above information is edited by the lookchem of Dai Xiongfeng.
Production method
It can be prepared from O-bromo-chlorobenzene (see 05820) by the following steps.
Toxicity grading
Poisoning.
Acute toxicity
Oral-rat; LD50> 5000 mg/kg; Oral-Mouse LD50> 4000 mg/kg.
Flammability and hazard properties
Thermal decomposition can release toxic chloride fume.
Storage characteristics
Low-temperature, dry and ventilated warehouse.
Extinguishing media
Water, carbon dioxide, foam, powder.
Indications
Mitotane (Lysodren) produces selective atrophy of the
zona fasciculata and zona reticularis, which results in a
decrease in the secretion of 17-hydroxycorticosteroids.
Direct inhibition of cholesterol side-chain cleavage and
11/18-hydroxylase activities has also been demonstrated.
Indications
The observation that mitotane (Lysodren) could produce
adrenocortical necrosis in animals led to its use in
the palliation of inoperable adrenocortical adenocarcinomas.
A reduction in both tumor size and adrenocortical
hormone secretion can be achieved in about half of
the patients taking the drug. Because normal adrenocortical
cells also are affected, endogenous glucocorticoid
production should be monitored and replacement
therapy administered when appropriate.
Mitotane is incompletely absorbed from the gastrointestinal
tract after oral administration. However,
once absorbed, it tends to accumulate in adipose tissue.
Mitotane is slowly excreted and will appear in the urine
for several years.The major toxicities associated with its
use are anorexia, nausea, diarrhea, lethargy, somnolence,
dizziness, and dermatitis.
Manufacturing Process
From dichloroacetaldehyde and 2-chlorphenylmagnesiumbromide was
prepared 1-(2-chlorphenyl-2,2-dichloroethanol. By action of H2SO4 on 1-(2-
chlorphenyl)-2,2-dichloroethanol in chlorobenzene was prepared 1,1-dichloro-
2,2-bis(2,4'-dichlorophenyl)ethane.
Therapeutic Function
Antineoplastic
Air & Water Reactions
Insoluble in water.
Reactivity Profile
Mitotan dehydrohalogenates with strong alkalis. Simple aromatic halogenated organic compounds are very unreactive; halogenated aliphatic compounds are moderately or very reactive. For both subgroups, reactivity generally decreases with increased degree of substitution of halogen for hydrogen atoms. Materials in this group are incompatible with strong oxidizing and reducing agents. Also, they are incompatible with many amines, nitrides, azo/diazo compounds, alkali metals, and epoxides.
Fire Hazard
Flash point data for Mitotan are not available. Mitotan is probably combustible.
Pharmacology
Mitotane, a derivative of the insecticide DDT, quickly lowers the level of corticosteroids,
and is metabolized in the blood and urine and used on non-operable metastatic prostate
carcinomas. Synonyms of this drug are lysodren and others.
Clinical Use
Mitotane is the drug of choice for the treatment of
primary adrenal carcinoma when surgery or radiation
therapy is not feasible. Its effectiveness
in curtailing adrenal activity is due to an action on
adrenocortical mitochondria to impair cytochrome
P450 steps in steroid biosynthesis. Mitotane requires
metabolic transformation to exert its therapeutic action,
and the differential ability of tumors to metabolize
the drug may determine its clinical effectiveness. It is
advised to measure serum mitotane levels and urinary
free cortisol excretion to ensure adequate therapeutic
concentrations. Mitotane increases circulating cholesterol
by inhibiting cytochrome P450–mediated reactions
and therefore contributes to the cardiovascular
events that are a significant cause of mortality in untreated
Cushing’s syndrome.
Mitotane, being closely related to the organochlorine
insecticides, shares its inductive effects on the liver
microsomal drug-metabolizing enzyme system, and its
use may therefore alter the requirement for concomitantly
administered drugs that are also metabolized by
this pathway.
Side effects
Mitotane is capable of inducing remission of
Cushing’s disease, but only after several weeks of therapy
and at the price of severe gastrointestinal distress.
Moreover, more than half of patients relapse following
cessation of therapy. Other side effects include lethargy,
mental confusion, skin rashes, and altered hepatic function.
Being a lipid-soluble substance, mitotane remains
stored in body tissues for extended periods. This may
account for the marked patient-to-patient variability in
its therapeutic and/or toxic effects.
Synthesis
Mitotane, 1,1-dichloro-2-(o-chlorophenyl)ethane (30.5.8), is made by alkylating
chlorobenzene with 1-(2-chlorophenyl)-2,2-dichloroethane (30.5.7) in the presence of sulfuric acid. The necessary 1-(2-chlorophenyl)-2,2-dichloroethanol (30.5.7) is in turn made
from reacting 2-chlorophenylmagnesiumbromide with dichloroacetic aldehyde.
Veterinary Drugs and Treatments
In veterinary medicine, mitotane is used primarily for the medical
treatment of pituitary-dependent hyperadrenocorticism (PDH),
principally in the dog. It has also been used for the palliative treatment
of adrenal carcinoma in humans and dogs.
Drug interactions
Potentially hazardous interactions with other drugs
Anticoagulants: possibly reduced anticoagulant effect
of coumarins.
Antipsychotics: avoid with clozapine (increased risk
of agranulocytosis).
Diuretics: avoid with spironolactone.
Metabolism
Metabolised in the liver and other tissues and excreted as
metabolites in urine and bile. From 10-25% of a dose has
been recovered in the urine as a water-soluble metabolite
and 1-17% in the faeces as metabolites
Purification Methods
Purify Mitotane by recrystallisation from pentane, MeOH or EtOH. It is soluble in isooctane and CCl4. [Haller et al. J Am Chem Soc 67 1600 1945, Beilstein 5 IV 1883.]
Check Digit Verification of cas no
The CAS Registry Mumber 53-19-0 includes 5 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 2 digits, 5 and 3 respectively; the second part has 2 digits, 1 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 53-19:
(4*5)+(3*3)+(2*1)+(1*9)=40
40 % 10 = 0
So 53-19-0 is a valid CAS Registry Number.
InChI:InChI=1/C14H10Cl4/c15-10-7-5-9(6-8-10)13(14(17)18)11-3-1-2-4-12(11)16/h1-8,13-14H
53-19-0Relevant articles and documents
Visible-light-promoted oxidative halogenation of alkynes
Li, Yiming,Mou, Tao,Lu, Lingling,Jiang, Xuefeng
supporting information, p. 14299 - 14302 (2019/12/02)
In nature, halogenation promotes the biological activity of secondary metabolites, especially geminal dihalogenation. Related natural molecules have been studied for decades. In recent years, their diversified vital activities have been explored for treating various diseases, which call for efficient and divergent synthetic strategies to facilitate drug discovery. Here we report a catalyst-free oxidative halogenation achieved under ambient conditions (halide ion, air, water, visible light, room temperature, and normal pressure). Constitutionally, electron transfer between the oxygen and halide ion is shuttled via simple conjugated molecules, in which phenylacetylene works as both reactant and catalyst. Synthetically, it provides a highly compatible late-stage transformation strategy to build up dihaloacetophenones (DHAPs).
THERAPEUTIC FOR HEPATIC CANCER
-
, (2011/02/18)
A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.
Anti-Claudin 3 Monoclonal Antibody and Treatment and Diagnosis of Cancer Using the Same
-
, (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.
Facile and catalytic degradation method of DDT using Pd/C-Et3N system under ambient pressure and temperature
Monguchi, Yasunari,Kume, Akira,Sajiki, Hironao
, p. 8384 - 8392 (2007/10/03)
The catalytic degradation method of p,p′-DDT [1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane] and its regioisomer o,p′-DDT [1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane] using the Pd/C-Et3N system under ambient hydrogen pressure and temperature was established. The presence of Et3N was necessary for the quick and complete breakdown of DDT. The independent degradation study of two intermediates, p,p′-DDD [2,2-bis(p-chlorophenyl)-1,1-dichloroethane] and p,p′-DDE [2,2-bis(p-chlorophenyl)-1,1-dichloroethylene] using GC-MS let us to speculate the degradation pathway of p,p′-DDT. In the initial phase of the reaction, p,p′-DDT degradation splits into two ways: a dehydrochlorination pathway and a hydrodechlorination pathway. In each pathway, reaction starts from an aliphatic moiety and subsequent hydrodechlorination from the benzene moieties takes place in a stepwise manner. The former pathway leads to the formation of 1,1-diphenylethane and the latter leads to the formation of 1,1-dichloro-2,2-diphenylethane. These diphenylethane analogs, which are less toxic compared with p,p′-DDT, are terminal degradation products in our system. The distinctive features of our catalytic degradation method of DDTs are reliability, simplicity, efficiency, and inexpensiveness.
Isomer-selective and enantiomerselective determination of DDT and related compounds using chiral high-resolution gas chromatography/mass spectrometry and chiral high-performance liquid chromatography
Buser, Hans-Rudolf,Mueller, Markus D.
, p. 2691 - 2698 (2007/10/02)
The composition of technical DDT was investigated using achiral and chiral high-resolution gas chromatography (HRGC) and electron-ionization mass spectrometry (EIMS). 2,4′-DDT and 2,4′-DDD, two important components of technical DDT, were enantiomerically resolved by chiral HRGC with silylated β-cyclodextrin and by chiral high-performance chromatography (HPLC) with permethylated γ-cyclodextrin as chiral selectors. The (+)- and (-)- enantiomers were assigned by chiral HPLC using chiroptical measurements. Enantiopure isolates were then used to identify these enantiomers in chiral HRGC analyses. Previous data indicated (+)- and (-)-2,4′-DDT to have S- and R-configuration, respectively, but the absolute configurations for (+)- and (-)-2,4′-DDD were hitherto unknown. They were now assigned via the reductive dechlorination of the individual 2,4′-DDT enantiomers which proceeded stereoselectively to the corresponding 2,4′-DDD enantiomers. The results showed (+)- and (-)-2,4′-DDD to have R- and S-configuration, respectively. The enantiomers of 2,4′-DDD thus have reversed signs of rotation for polarized light compared to the enantiomers of 2,4′-DDT with the same configuration. The enantiomer resolution of several additional chiral compounds in technical DDT is reported; enantiomeric ratios of ≈1.0 indicated all chiral compounds to be present as racemates in the technical and in the synthetic reference materials. We report the first enantioselective determinations of technical DDT; the methods presented should also be applicable to the analysis of environmental and biological samples.
Method of treating nausea and vomiting with certain substituted-phenylalkylamino (and aminoacid) derivatives and other serotonin depleting agents
-
, (2008/06/13)
A method for the treatment of emesis in a mammal, which method comprises administering to said mammal an emesis inhibiting amount of a compound which depletes serotonin in the brain of mammals; among which are compounds having the formula: STR1 wherein, R is selected from hydrogen, loweralkyl, trifluoromethyl, carboxyl, or loweralkoxycarbonyl; R1 and R2 are hydrogen or loweralkyl; Z is trifluoromethyl or halogen; the optical isomers and pharmaceutically acceptable salts thereof; two of the preferred compounds of the invention are fenfluramine and norfenfluramine.
