Mitotane

Base Information

• Chemical Name: Mitotane
• CAS No.: 53-19-0
• Molecular Formula: C14H10Cl4
• Molecular Weight: 320.045
• Hs Code.: 2903990002
• European Community (EC) Number: 200-166-6
• NSC Number: 755849,38721
• UNII: 78E4J5IB5J
• DSSTox Substance ID: DTXSID9020372
• Nikkaji Number: J1.366H
• Wikipedia: Mitotane
• Wikidata: Q417465
• NCI Thesaurus Code: C664
• RXCUI: 7004
• Pharos Ligand ID: SQALPCX5Y21A
• Metabolomics Workbench ID: 42968
• ChEMBL ID: CHEMBL1670
• Mol file: 53-19-0.mol

Synonyms:Chloditan;Chlodithane;Khloditan;Lysodren;Mitotane;Mytotan;o,p-DDD;ortho,para DDD;ortho,para-DDD

Chemical Property of Mitotane

Chemical Property:

• Appearance/Colour: Crystalline Solid
• Melting Point: 77-78 °C(lit.)
• Refractive Index: 1.6000 (estimate)
• Boiling Point: 398.9 °C at 760 mmHg
• Flash Point: 194.2 °C
• PSA: 0.00000
• Density: 1.372 g/cm³
• LogP: 5.92900
• Storage Temp.: APPROX 4°C
• Solubility.: DMSO: soluble20mg/mL, clear
• Water Solubility.: <0.1 g/100 mL at 24℃
• XLogP3: 6.2
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 0
• Rotatable Bond Count: 3
• Exact Mass: 319.950711
• Heavy Atom Count: 18
• Complexity: 248

Purity/Quality:

99%min ^*data from raw suppliers

Mitotane ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn
• Hazard Codes: Xn
• Statements: 40
• Safety Statements: 36/37

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antineoplastic Agents
• Canonical SMILES: C1=CC=C(C(=C1)C(C2=CC=C(C=C2)Cl)C(Cl)Cl)Cl
• Recent ClinicalTrials: Cisplatin-Based Chemotherapy and/or Surgery in Treating Young Patients With Adrenocortical Tumor
• Recent EU Clinical Trials: Multicenter randomized open-label phase III trial of Adjuvant Chemotherapy vs. observation or mitotane after primary surgical resection of localized
• Uses: It belongs to antineoplastic agents and can be used for the treatment of adrenal cortical carcinoma. insecticide, antineoplastic aminobiphoshphanate for treatment of osteoporosis and Paget's bone disease Mitotane is an inhibitor of steroidogenesis that suppresses the growth of adrenocortical cells. It blocks the expression of several genes that encode proteins involved in steroidogenesis and disrupts mitochondrial respiratory chain activity in human adrenocortical cells. Mitotane has anti-neoplastic actions, alone or in combination with other compounds, and suppresses cortisol synthesis, although it also has significant toxicity in the gastrointestinal tract and nervous system. It is effective against adrenocortical carcinoma and Cushing’s Syndrome in clinical trials. An Antineoplastic. Used as an adrenolytic agent
• Production method: It can be prepared from O-bromo-chlorobenzene (see 05820) by the following steps.
• Description: Mitotane is an inhibitor of steroidogenesis that suppresses the growth of adrenocortical cells. It blocks the expression of several genes that encode proteins involved in steroidogenesis and disrupts mitochondrial respiratory chain activity in human adrenocortical cells. Mitotane has anti-neoplastic actions, alone or in combination with other compounds, and suppresses cortisol synthesis, although it also has significant toxicity in the gastrointestinal tract and nervous system. It is effective against adrenocortical carcinoma and Cushing’s Syndrome in clinical trials.
• 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. 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.
• Therapeutic Function: Antineoplastic
• 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.
• 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.

Technology Process of Mitotane

There total 13 articles about Mitotane 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: 89.0%

2,2‐dichloro‐1‐(2‐chlorophenyl)ethan‐1‐one (24123-67-9) + chlorobenzene (108-90-7) → 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (53-19-0,102976-58-9)

Guidance literature:

2,2‐dichloro‐1‐(2‐chlorophenyl)ethan‐1‐one; With sodium tetrahydroborate; In methanol; at 20 ℃; for 0.333333h; Schlenk technique; Inert atmosphere;

chlorobenzene; With sulfuric acid; at 20 ℃; for 0.166667h;

DOI:10.1039/c9cc07655g

Reference yield: 71.0%

2,2-dichloro-1-(2-chlorophenyl)ethanol (27683-60-9) + chlorobenzene (108-90-7) → 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (53-19-0,102976-58-9)

Guidance literature:

With sulfuric acid; at 35 ℃; for 6h;

DOI:10.1007/BF00776800

Reference yield: 42.0%

o,p'-DDT (789-02-6,58633-26-4) → 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (53-19-0,102976-58-9) + 1-(p-chlorophenyl)-1-phenylethane (60617-89-2) + 1-(o-chlorophenyl)-1-(p-chlorophenyl)ethane (77008-62-9) + 1-(2-chloro-phenyl)-1-phenyl-ethane (76690-79-4)

Guidance literature:

With hydrogen; triethylamine; palladium on activated charcoal; In methanol; at 20 ℃; for 0.166667h;

DOI:10.1016/j.tet.2006.06.041

upstream raw materials:

p,p'-DDT

2,2-dichloro-1-(2-chlorophenyl)ethanol

chlorobenzene

o,p'-DDT

Downstream raw materials:

1-Chloro-2-o-chlorophenyl-2-p'-chlorophenylethylene

C₁₄H₉Cl₃

1-chloro-2-(2-chlorophenyl)-2-(4-chlorophenyl)ethane

(R)-(+)-1,1-dichloro-2-(2-chlorophenyl)-2-(4-chlorophenyl)ethane

Refernces

• 1、 -. "THERAPEUTIC FOR HEPATIC CANCER". . . Retrieved 2011/02/18.
• 2、 Monguchi, Yasunari,Kume, Akira,Sajiki, Hironao. "Facile and catalytic degradation method of DDT using Pd/C-Et3N system under ambient pressure and temperature". . p. 8384 - 8392. Retrieved 2007/10/03.