Clofazimine

Base Information

• Chemical Name: Clofazimine
• CAS No.: 2030-63-9
• Molecular Formula: C27H22Cl2N4
• Molecular Weight: 473.404
• Hs Code.: 35040000
• European Community (EC) Number: 217-980-2
• NSC Number: 759283,141046
• UNII: D959AE5USF
• DSSTox Substance ID: DTXSID7022839
• Nikkaji Number: J9.543E
• Wikipedia: Clofazimine
• Wikidata: Q418611,Q105302601
• NCI Thesaurus Code: C47456
• Pharos Ligand ID: GKXYGK77W4KM
• Metabolomics Workbench ID: 49989
• ChEMBL ID: CHEMBL1292,CHEMBL1083384
• Mol file: 2030-63-9.mol

Synonyms:B 663;B-663;B663;Clofazimine;G 30,320;G-30,320;G30,320;Lamprene;N,5-Bis(4-chlorophenyl)-3,5-dihydro-3-((1-methylethyl)imino)-2-phenazinamine

Chemical Property of Clofazimine

Chemical Property:

• Melting Point: 210-212°
• Refractive Index: 1.666
• Boiling Point: 566.9 °C at 760 mmHg
• PKA: 8.37; also reported as 8.51(at 25℃)
• Flash Point: 296.7 °C
• PSA: 42.21000
• Density: 1.29 g/cm³
• LogP: 7.61120
• Storage Temp.: 2-8°C
• Solubility.: Practically insoluble in water, soluble in methylene chloride, very slightly soluble in ethanol (96 per cent). It shows polymorphism (5.9).
• Water Solubility.: 10mg/L(temperature not stated)
• XLogP3: 7.1
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 4
• Exact Mass: 472.1221521
• Heavy Atom Count: 33
• Complexity: 829

Purity/Quality:

99.9% ^*data from raw suppliers

Clofazimine >98.0%(HPLC)(T) ^*data from reagent suppliers

Safty Information:

• Pictogram(s): Xn, Xi
• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38
• Safety Statements: 36-26

MSDS Files:

SDS file from LookChem

Useful:

• Drug Classes: Antiinfective Agents
• Canonical SMILES: CC(C)N=C1C=C2C(=NC3=CC=CC=C3N2C4=CC=C(C=C4)Cl)C=C1NC5=CC=C(C=C5)Cl
• Recent ClinicalTrials: Study of Mycobacterial Infections
• Recent EU Clinical Trials: Pharmacokinetic study with a loading dose of clofazimine in adult patients with nontuberculous mycobacterial disease
• Uses: Antibacterial (tuberculostatic, leprostatic). antiinflammatory, glucocorticoid
• Indications: Clofazimine is a weakly bactericidal dye that has some activity against M. leprae. Its precise mechanism of action is unknown but may involve mycobacterial DNA binding. Its oral absorption is quite variable, with 9 to 70% of the drug eliminated in the feces. Clofazimine achieves significant concentrations in tissues, including the phagocytic cells; it has a plasma half-life of 70 days. It is primarily excreted in bile, with less than 1% excretion in urine.
• Clinical Use: Clofazimine (Lamprene) is a basic red dye that exerts a slow bactericidal effect on M. leprae, the bacterium that causes leprosy. It occurs as a dark red crystalline solid that is insoluble in water. Clofazimine is used in the treatment of lepromatous leprosy, including dapsone-resistant forms of the disease. In addition to its antibacterial action, the drug appears to possess anti-inflammatory and immune-modulating effects that are of value in controlling neuritic complications and in suppressing erythema nodosum leprosum reactions associated with lepromatous leprosy. It is frequently used in combination with other drugs, such as dapsone or rifampin.The mechanisms of antibacterial and anti-inflammatory actions of clofazimine are not known. The drug is known to bind to nucleic acids and concentrate in reticuloendothelial tissue. It can also act as an electron acceptor and may interfere with electron transport processes. The oral absorption of clofazimine is estimated to be about 50%. It is a highly lipid-soluble drug that is distributed into lipoidal tissue and the reticuloendothelial system. Urinary excretion of unchanged drug and metabolites is negligible. Its half-life after repeated dosage is estimated to be about 70 days. Severe gastrointestinal intolerance to clofazimine is relatively common. Skin pigmentation, ichthyosis and dryness, rash, and pruritus also occur frequently. Clofazimine has also been used to treat skin lesions caused by Mycobacterium ulcerans. Multibacillary leprosy (in combination with other anti-leprosy drugs) Erythema nodosum leprosum (anti-inflammatory activity) Clofazimine has been suggested as a drug for treatment of MDR tuberculosis, although its efficacy is unproven. It has been used to treat M. ulcerans infection (Buruli ulcer) but with limited responses. Use in disease caused by mycobacteria of the M. avium complex is no longer recommended as more effective and less toxic alternative agents are available. Clofazimine is given to treat sulfone-resistant leprosy or to patients who are intolerant to sulfones. It also exerts an antiinflammatory effect and prevents erythema nodosum leprosum, which can interrupt treatment with dapsone.This is a major advantage of clofazimine over other antileprosy drugs. Ulcerative lesions caused by Mycobacterium ulcerans respond well to clofazimine. It also has some activity against M. tuberculosis and can be used as last resort therapy for the treatment of MDR tuberculosis.
• Drug interactions: Potentially hazardous interactions with other drugs Antibacterials: increased risk of ventricular arrhythmias with bedaquiline.

Technology Process of Clofazimine

There total 3 articles about Clofazimine 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:

isopropylamine (75-31-0) + N,5-bis(4-chlorophenyl)-3-imino-3,5-dihydrophenazin-2-amine (102262-55-5) → clofazimine (2030-63-9)

Guidance literature:

In 1,4-dioxane; Reflux;

Reference yield:

1,5-bis-(4-chloro-phenyl)-2,2-dimethyl-2,5-dihydro-1H-imidazo[4,5-b]phenazine (84803-71-4) → clofazimine (2030-63-9)

Guidance literature:

With ethanol; platinum; Hydrogenation;

Reference yield:

3-amino-2-(4-chloro-anilino)-5-(4-chloro-phenyl)-phenazinium; chloride + isopropylamine (75-31-0) → clofazimine (2030-63-9)

Guidance literature:

upstream raw materials:

1,5-bis-(4-chloro-phenyl)-2,2-dimethyl-2,5-dihydro-1H-imidazo[4,5-b]phenazine

isopropylamine

N,5-bis(4-chlorophenyl)-3-imino-3,5-dihydrophenazin-2-amine

Downstream raw materials:

5-(4-chloro-phenyl)-2-(2,N-dibromo-4-chloro-anilino)-3-isopropylamino-phenazinium betaine

C₂₇H₂₂Cl₂N₄*C₃H₄O₄

C₂₇H₂₂Cl₂N₄*C₇H₆O₃

C₂₇H₂₂Cl₂N₄*C₆H₅NO₂

Refernces