(3E)-N,5-bis(4-chlorophenyl)-3-[(propan-2-yl)imino]-3,5-dihydrophenazin-2-amine

• ChemBase ID: 723
• Molecular Formular: C27H22Cl2N4
• Molecular Mass: 473.39638
• Monoisotopic Mass: 472.12215208
• SMILES: Clc1ccc(n2c3c(nc4c2cccc4)cc(Nc2ccc(Cl)cc2)/c(=N/C(C)C)/c3)cc1
• Canonical SMILES: Clc1ccc(cc1)Nc1cc2nc3ccccc3n(c2c/c/1=N\C(C)C)c1ccc(cc1)Cl
• InChI: InChI=1S/C27H22Cl2N4/c1-17(2)30-24-16-27-25(15-23(24)31-20-11-7-18(28)8-12-20)32-22-5-3-4-6-26(22)33(27)21-13-9-19(29)10-14-21/h3-17,31H,1-2H3/b30-24+
• InChIKey: WDQPAMHFFCXSNU-BGABXYSRSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: (3E)-N,5-bis(4-chlorophenyl)-3-[(propan-2-yl)imino]-3,5-dihydrophenazin-2-amine
• IUPAC Traditional name: clofazimine; lamprene
• Brand Name: Lampren; Lamprene
• Synonyms: N,5-Bis(4-chlorophenyl)-3,5-dihydro-3-(isopropylimino)phenazin-2-amine; Clofazimine; N,5-Bis(4-chlorophenyl)-3,5-dihydro-3-[(1-methylethyl)imino]-2-phenazinamine; 3-(p-Chloroanilino)-10-(p-chlorophenyl)-2,10-dihydro-2-(isopropylimino)phenazine; 2-(4-Chloroanilino)-3-isopropylimino-5-(4-chlorophenyl)-3,5-dihydrophenazine; B 663; Hansepran; Lampren; Lamprene; NSC 141046; Clofazimina [INN-Spanish]; Chlofazimine; Clofaziminum [INN-Latin]; Clofazimine

Database IDs

• CAS Number: 2030-63-9
• EC Number: 217-980-2
• MDL Number: MFCD00056793
• PubChem SID: 160964186; 24893114
• PubChem CID: 2794

CALCULATED PROPERTIES

JChem

• Acid pKa: 16.154114
• H Acceptors: 4
• H Donor: 1
• LogD (pH = 5.5): 4.042732
• LogD (pH = 7.4): 5.4225707
• Log P: 7.304315
• Molar Refractivity: 142.5521 cm^3
• Polarizability: 51.55547 Å^3
• Polar Surface Area: 39.99 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 7.39
• LOG S: -5.5
• Solubility (Water): 1.51e-03 g/l

PROPERTIES

Physical Property

• Solubility: 0.225 mg/L (virtually insoluble); Chloroform; Ethyl Acetate
• Apperance: Red Solid
• Melting Point: 224-226°C (dec.)
• Hydrophobicity(logP): 7

Safety Information

• Storage Condition: Refrigerator
• RTECS: SG1578000
• German water hazard class: 3
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves

Pharmacology Properties

• Target: Others

Product Information

• Salt Data: Free Base

DETAILS

DrugBank - DB00845

• Drug Groups: approved
• Description: A fat-soluble riminophenazine dye used for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum. (From AMA Drug Evaluations Annual, 1993, p1619)
• Indication: For the treatment of lepromatous leprosy, including dapsone-resistant lepromatous leprosy and lepromatous leprosy complicated by erythema nodosum leprosum.
• Pharmacology: Clofazimine exerts a slow bactericidal effect on Mycobacterium leprae (Hansen's bacillus). Clofazimine inhibits mycobacterial growth and binds preferentially to mycobacterial DNA. Clofazimine also exerts antiinflammatory properties in controlling erythema nodosum leprosum reactions. Clofazimine is highly lipophilic and tends to be deposited predominantly in fatty tissue and in cells of the reticuloendothelial system. It is taken up by macrophages throughout the body. Measurement of the minimum inhibitory concentration (MIC) of clofazimine against leprosy bacilli in vitro is not yet feasible. In the mouse footpad system, the multiplication of M.leprae is inhibited by introducing 0.0001%- 0.001% clofazimine in the diet. Although bacterial killing may begin shortly after starting the drug, it cannot be measured in biopsy tissues taken from patients for mouse footpad studies until approximately 50 days after the start of therapy.
• Toxicity: Oral, rabbit: LD₅₀ = 3.3 g/kg; Oral, mouse: LD₅₀ = > 4 g/kg. Severe abdominal symptoms have necessitated exploratory laparotomies in some patients on clofazimine therapy. Rare reports have included splenic infarction, bowel obstruction, and gastrointestinal bleeding. Deaths have been reported, following severe abdominal symptoms.
• Affected Organisms: Mycobacteria
• Biotransformation: Hepatic. Three metabolites have been identified - two conjugated and one unconjugated, however, it is not yet known whether these metabolites are pharmacologically active. Metabolite I is formed by hydrolytic dehalogenation of clofazimine, metabolite II presumably is formed by a hydrolytic deamination reaction followed by glucuronidation, and metabolite III appears to be a hydrated clofazimine glucuronide.
• Absorption: Absorption varies from 45 to 62% following oral administration in leprosy patients. Bioavailability is approximately 70%. Food increases bioavailability and rate of absorption.
• Half Life: 10 days following a single dose, 70 days after long-term, high-dose therapy.
• External Links: Wikipedia; RxList; Drugs.com

Toronto Research Chemicals - C324300

Antibacterial (tuberculostatic, leprostatic).

REFERENCES

• Doak, A., et al.: J. Med. Chem., 53, 4259 (2010)
• Rodgers, A., et al.: Chem. Res. Toxicol., 23, 724 (2010)
• Gohil, V., et al.: Nat. Biotechnol., 28, 249 (2010)