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

• ChemBase编号: 723
• 分子式: C27H22Cl2N4
• 平均质量: 473.39638
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: (3E)-N,5-bis(4-chlorophenyl)-3-[(propan-2-yl)imino]-3,5-dihydrophenazin-2-amine
• IUPAC传统名: clofazimine; lamprene
• 商标名: Lampren; Lamprene
• 别名: 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

登记号

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

理论计算性质

JChem

• Acid pKa: 16.154114
• 质子受体: 4
• 质子供体: 1
• LogD (pH = 5.5): 4.042732
• LogD (pH = 7.4): 5.4225707
• Log P: 7.304315
• 摩尔折射率: 142.5521 cm^3
• 极化性: 51.55547 Å^3
• 极化表面积: 39.99 Å^2
• 可自由旋转的化学键: 4
• 里宾斯基五规则: false

ALOGPS 2.1

• Log P: 7.39
• LOG S: -5.5
• 溶解度: 1.51e-03 g/l

分子性质

理化性质

• 溶解度: 0.225 mg/L (virtually insoluble); Chloroform; Ethyl Acetate
• 外观: Red Solid
• 熔点: 224-226°C (dec.)
• 疏水性(logP): 7

安全信息

• 保存条件: Refrigerator
• RTECS编号: SG1578000
• 德国WGK号: 3
• 个人保护装置: dust mask type N95 (US), Eyeshields, Gloves

药理学性质

• 作用靶点: Others

产品相关信息

• 成盐信息: Free Base

详细说明

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).

参考文献

• 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)