1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole

• ChemBase ID: 142
• Molecular Formular: C22H17ClN2
• Molecular Mass: 344.83678
• Monoisotopic Mass: 344.10802623
• SMILES: Clc1c(C(n2ccnc2)(c2ccccc2)c2ccccc2)cccc1
• Canonical SMILES: Clc1ccccc1C(n1cncc1)(c1ccccc1)c1ccccc1
• InChI: InChI=1S/C22H17ClN2/c23-21-14-8-7-13-20(21)22(25-16-15-24-17-25,18-9-3-1-4-10-18)19-11-5-2-6-12-19/h1-17H
• InChIKey: VNFPBHJOKIVQEB-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole
• IUPAC Traditional name: lotrimin; 1-[(2-chlorophenyl)diphenylmethyl]-1H-imidazole; clotrimazole
• Brand Name: Lotrimin AF, Mycelex; Canesten; Canesten 1-Day Cream Combi-Pak; Canesten 1-Day Therapy; Canesten 3-Day Therapy; Canesten 6-Day Therapy; Canesten Combi-Pak 1-Day Therapy; Canesten Combi-Pak 3-Day Therapy; Canesten Cream; Canesten Solution; Canestine; Canifug; Cimitidine; Clotrimaderm; Empecid; FemCare; Gyne lotrimin; Gyne-Lotrimin 3; Gyne-Lotrimin 3 Combination Pack; Gyne-Lotrimin Combination Pack; Gyne-lotrimin; Gynix; Lotrimin; Lotrimin AF Cream; Lotrimin AF Jock-Itch Cream; Lotrimin AF Lotion; Lotrimin AF Solution; Lotrimin Af; Lotrimin Cream; Lotrimin Lotion; Lotrimin Solution; Mono-baycuten; Mycelax; Mycelex; Mycelex 7; Mycelex Cream; Mycelex G; Mycelex Solution; Mycelex Troches; Mycelex Twin Pack; Mycelex-7; Mycelex-7 Combination Pack; Mycelex-G; Myclo Cream; Myclo Solution; Myclo Spray Solution; Myclo-Gyne; Mycosporin; Mykosporin; Neo-Zol Cream; Trimysten; Trivagizole 3; Veltrim
• Synonyms: Clotrimazole; 1-(o-Chlorotrityl)imidazole; 1-(o-Chloro-α,α-diphenylbenzyl)imidazole; 1-[(2-Chlorophenyl)diphenylmethyl]-1H-imidazole; Clotrimazol; Chlotrimazole; Clotrimazole; Lotrimin; Mycelex; Canesten; Clotrimazole(Canesten); 1-[(2-Chlorophenyl)-diphenyl-methyl]-1H-imidazole; FB-5097; Bay b 5097; Canifug; Empecid; Mycofung; Desamix F; Diphenyl(2-chlorophenyl)(1-imidazolyl)methane; Femcare; Gyne-Lotrimin; Gyne-Lotrimin 7; Locasten; 1-((2-chlorophenyl)diphenylmethyl)-1h-imidazole; 1-[(2-氯苯基)二苯甲基]-1H-咪唑; 三苯氯甲咪唑; 氯苯甲咪唑; 克霉唑

Database IDs

• CAS Number: 23593-75-1
• EC Number: 245-764-8
• MDL Number: MFCD00057220
• PubChem SID: 24860592; 46507927; 160963605; 24278327
• PubChem CID: 2812
• CHEBI ID: 3764
• ATC CODE: D01AC01; QJ02AB90; A01AB18; G01AF02
• CHEMBL: 104
• Chemspider ID: 2710
• DrugBank ID: DB00257
• KEGG ID: D00282
• Unique Ingredient Identifier: G07GZ97H65
• Wikipedia Title: Clotrimazole
• Medline Plus: a682753

CALCULATED PROPERTIES

JChem

• H Acceptors: 1
• H Donor: 0
• LogD (pH = 5.5): 5.3291874
• LogD (pH = 7.4): 5.7905
• Log P: 5.839452
• Molar Refractivity: 103.7645 cm^3
• Polarizability: 39.57285 Å^3
• Polar Surface Area: 17.82 Å^2
• Rotatable Bonds: 4
• Lipinski's Rule of Five: false

ALOGPS 2.1

• Log P: 5.48
• LOG S: -5.37
• Solubility (Water): 1.47e-03 g/l

PROPERTIES

Physical Property

• Solubility: 29.84 mg/mL; Chloroform; DMSO; Ethyl Acetate
• Apperance: White Solid
• Melting Point: 142-144°C
• Hydrophobicity(logP): 6.1

Safety Information

• Storage Condition: -20°C; Refrigerator; Room Temperature (15-30°C)
• RTECS: NI4377000
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 22-36/38; R:22
• Safety Statements: 26-36; S:36/37/39
• GHS Pictograms: GHS07
• GHS Signal Word: Warning
• GHS Hazard statements: H302-H315-H319
• GHS Precautionary statements: P305 + P351 + P338
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves

Pharmacology Properties

• Admin Routes: topical
• Bioavailability: Poorly and erratically absorbed orally
• Half Life: 2 hours
• Metabolism: hepatic
• Protein Bound: 90%
• Legal Status: P (UK)
• Pregnancy Category: A (Australia); C (oral) and B (topical) (US)
• Gene Information: human ... ABCB1(5243), CYP17A1(1586), CYP3A4(1576)mouse ... Abcb1a(18671), Abcb1b(18669)
• Mechanism of Action: Appears to increase permeability of fungal-cell-membrane causing leakage of intracellular components.; Functions as Lanosterol C-14 demethylation inhibitor; Induces K+ release from Trichophyton mentagrophytes mycelium; Induces membrane disruption; Potent cytochrome P-450b and P-450c inhibitor

Product Information

• Purity: 98%
• Grade: VETRANAL™, analytical standard
• Salt Data: Free Base
• Application(s): Antifungal agent
• Pharmacopeia Traceability: traceable to BP 379; traceable to PhEur C2430000; traceable to USP 1141002
• Empirical Formula (Hill Notation): C22H17ClN2

DETAILS

MP Biomedicals - 02198944

Specific inhibitor of Ca^2+ activated K^+ channels.

DrugBank - DB00257

• Drug Groups: approved
• Description: An imidazole derivative with a broad spectrum of antimycotic activity. It inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. [PubChem]
• Indication: For the local treatment of oropharyngeal candidiasis and vaginal yeast infections, also used in fungal infections of the skin such as ringworm, athlete's foot, and jock itch.
• Pharmacology: Clotrimazole, an imidazole derivative with a broad spectrum of antimycotic activity, inhibits biosynthesis of the sterol ergostol, an important component of fungal cell membranes. Its action leads to increased membrane permeability and apparent disruption of enzyme systems bound to the membrane. Betamethasone and clotrimazole are used together to treat cutaneous tinea infections. In studies in fungal cultures, the minimum fungicidal concentration of clotrimazole caused leakage of intracellular phosphorous compounds into the ambient medium with concomitant breakdown of cellular nucleic acids, and accelerated potassium etflux. Both of these events began rapidly and extensively after addition of the drug to the cultures. The primary action of clotrimazole is against dividing and growing organisms.
• Toxicity: Symptoms of overdose include erythema, stinging, blistering, peeling, edema, pruritus, urticaria, burning, and general irritation of the skin, and cramps.
• Affected Organisms: Yeast and other fungi
• Biotransformation: Hepatic (metabolized to inactive metabolites)
• Absorption: Poorly and erratically absorbed orally, minimal vaginal or topical absorption.
• Half Life: 2 hours
• Protein Binding: 90%
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1606

Research Area: Infection
Biological Activity:
Clotrimazole(Canesten) is a synthetic, antifungal and broad-spectrum derivate of imidazole. Clotrimazole inhibits biosynthesis of sterols, particularly inhibiting ergosterol, which is an essential component of the fungal cell membrane, thereby damaging and affecting the permeability of the cell membrane. This results in the  leakage and the loss of essential intracellular compounds, and eventually causes the lysis of cell.  [1, 2]

Sigma Aldrich - C6019

Biochem/physiol Actions
Specific inhibitor of Ca2+-activated K+ channels. Antifungal azole. Antifungal mode of action: Inhibits cytochrome P450-dependent 14α-demethylase, which is critical to ergosterol biosynthesis. The accumulated 14α-methylated sterols change the membrane structure of sensitive fungi, altering cell membrane permeability.

Sigma Aldrich - 33894

Legal Information
VETRANAL is a trademark of Sigma-Aldrich Co. LLC

Toronto Research Chemicals - C587400

Clotrimazole is an antifungal agent.

REFERENCES

• http://en.wikipedia.org/wiki/Clotrimazole
• Podust, L., et al.: J. Biol. Chem., 284, 25211 (2009)
• Hollender, J., et al.: Environ. Sci. Technol., 43, 7862 (2009)
• Marciniec, B., et al.: J. Pharm. Biomed. Anal., 50, 675 (2009)
• McGinnity, D., et al.: Drug Metab. Disposition, 37, 1259 (2009)
• Buechel, K.H. et al., Arzneim.-Forsch., 1972, 22, 1260, (synth, pharmacol)
• Kracmar, J. et al., Cesk. Farm., 1977, 26, 345, (uv)
• Raab, W., Curr. Ther. Res., Clin. Exp., 1977, 22, 65, (pharmacol)
• Ruppert, J.F., Diss. Abstr. Int., B, 1977, 38, 2681, (synth)
• Hoogerheide, J.G. et al., Anal. Profiles Drug Subst., 1982, 11, 225, (rev)
• Lewis, D.F.V. et al., J. Biochem. Toxicol., 1989, 4, 231, (pharmacol)
• Martindale, The Extra Pharmacopoeia, 30th edn., Pharmaceutical Press, 1993, 320
• Negwer, M., Organic-Chemical Drugs and their Synonyms, 7th edn., Akademie-Verlag, 1994, 8792
• Song, H. et al., Acta Cryst. C, 1998, 54, 1675-1677, (cryst struct)
• Lewis, R.J., Sax's Dangerous Properties of Industrial Materials, 8th edn., Van Nostrand Reinhold, 1992, MRX500