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Identification
Name Butenafine
Accession Number DB01091 (APRD00833)
Type small molecule
Groups approved
Description

Butenafine hydrochloride is a synthetic benzylamine antifungal agent. Butenafine works by inhibiting the synthesis of sterols by inhibiting squalene epoxidase, an enzyme responsible for the creation of sterols needed in fungal cell membranes.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Butenafina [INN-Spanish]
  • Butenafine [INN]
  • Butenafine HCL
  • Butenafine hydrochloride
  • Butenafinum [INN-Latin]
Brand names
  • Lotrimin Ultra
  • Mentax
  • Mentax-tc
Brand name mixtures Not Available
Categories
  • Antifungal Agents
CAS number 101828-21-1
Weight Average: 317.4672
Monoisotopic: 317.214349869
Chemical Formula C23H27N
InChI Key InChIKey=ABJKWBDEJIDSJZ-UHFFFAOYSA-N
InChI
InChI=1S/C23H27N/c1-23(2,3)21-14-12-18(13-15-21)16-24(4)17-20-10-7-9-19-8-5-6-11-22(19)20/h5-15H,16-17H2,1-4H3
Plain Text
IUPAC Name
[(4-tert-butylphenyl)methyl](methyl)(naphthalen-1-ylmethyl)amine
SMILES
CN(CC1=CC=C(C=C1)C(C)(C)C)CC1=CC=CC2=C1C=CC=C2
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Naphthalenes
  • Cumenes and Derivatives
Substructures
  • Naphthalenes
  • Benzene and Derivatives
  • Cumenes and Derivatives
  • Aliphatic and Aryl Amines
  • Aromatic compounds
Pharmacology
Indication For the topical treatment of the following dermatologic infections: tinea (pityriasis) versicolor due to M. furfur, interdigital tinea pedis (athlete’s foot), tinea corporis (ringworm) and tinea cruris (jock itch) due to E. floccosum, T. mentagrophytes, T. rubrum, and T. tonsurans.
Pharmacodynamics Butenafine is a synthetic antifungal agent that is structurally and pharmacologically related to allylamine antifungals. The exact mechanism of action has not been established, but it is suggested that butenafine's antifungal activity is exerted through the alteration of cellular membranes, which results in increased membrane permeability, and growth inhibition. Butenafine is mainly active against dermatophytes and has superior fungicidal activity against this group of fungi when compared to that of terbinafine, naftifine, tolnaftate, clotrimazole, and bifonazole. It is also active against Candida albicans and this activity is superior to that of terbinafine and naftifine. Butenafine also generates low MICs for Cryptococcus neoformans and Aspergillus spp. as well.
Mechanism of action Although the mechanism of action has not been fully established, it has been suggested that butenafine, like allylamines, interferes with sterol biosynthesis (especially ergosterol) by inhibiting squalene monooxygenase, an enzyme responsible for converting squalene to 2,3-oxydo squalene. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Blockage of squalene monooxygenase also leads to a subsequent accumulation of squalene. When a high concentration of squalene is reached, it is thought to have an effect of directly kill fungal cells.
Absorption The total amount absorbed through the skin into the systemic circulation has not been quantified.
Volume of distribution Not Available
Protein binding Not Available
Metabolism

The primary metabolite in urine was formed through hydroxylation at the terminal t-butyl side-chain.
Route of elimination Not Available
Half life Following topical application, a biphasic decline of plasma butenafine concentrations was observed with the half-lives estimated to be 35 hours initial and over 150 hours terminal.
Clearance Not Available
Toxicity Not Available
Affected organisms
  • Fungi
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Schering plough healthcare products inc
  • Mylan pharmaceuticals inc
Packagers
Dosage forms
Form Route Strength
Cream Topical
Prices
Unit description Cost Unit
Mentax 1% Cream 30 gm Tube 124.7 USD tube
Mentax 1% Cream 15 gm Tube 50.99 USD tube
Mentax 1% cream 4.0 USD g
Lotrimin ultra 1% cream 0.68 USD g
Patents
Country Patent Number Approved Expires
United States 5021458 1993-10-18 2010-10-18
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
water solubility Slightly soluble (HCl salt) PhysProp
logP 6.6 PhysProp
Predicted Properties
Property Value Source
water solubility 7.56e-05 g/l ALOGPS
logP 5.85 ALOGPS
logP 6.17 ChemAxon Molconvert
logS -6.62 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 1 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 3.24 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 104.33 ChemAxon Molconvert
polarizability 38.41 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. McNeely W, Spencer CM: Butenafine. Drugs. 1998 Mar;55(3):405-12; discussion 413. Pubmed
  2. Singal A: Butenafine and superficial mycoses: current status. Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):999-1005. Pubmed
  3. Gupta AK: Butenafine: an update of its use in superficial mycoses. Skin Therapy Lett. 2002 Sep;7(7):1-2, 5. Pubmed
  4. Mingeot-Leclercq MP, Gallet X, Flore C, Van Bambeke F, Peuvot J, Brasseur R: Experimental and conformational analyses of interactions between butenafine and lipids. Antimicrob Agents Chemother. 2001 Dec;45(12):3347-54. Pubmed
  5. Syed TA, Maibach HI: Butenafine hydrochloride: for the treatment of interdigital tinea pedis. Expert Opin Pharmacother. 2000 Mar;1(3):467-73. Pubmed
  6. Reyes BA, Beutner KR, Cullen SI, Rosen T, Shupack JL, Weinstein MB: Butenafine, a fungicidal benzylamine derivative, used once daily for the treatment of interdigital tinea pedis. Int J Dermatol. 1998 Jun;37(6):450-3. Pubmed
  7. Iwatani W, Arika T, Yamaguchi H: Two mechanisms of butenafine action in Candida albicans. Antimicrob Agents Chemother. 1993 Apr;37(4):785-8. Pubmed
External Links
Resource Link
KEGG Compound C08067 Link_out
PubChem Compound 2484 Link_out
PubChem Substance 46506191 Link_out
ChemSpider 2390 Link_out
ChEBI 3238 Link_out
ChEMBL 3238 Link_out
Therapeutic Targets Database DAP001236 Link_out
PharmGKB PA448698 Link_out
Drug Product Database 2231063 Link_out
RxList http://www.rxlist.com/cgi/generic2/butenafine.htm Link_out
Drugs.com http://www.drugs.com/cdi/butenafine-cream.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Butenafine Link_out
ATC Codes
  • D01AE23
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (1.4 MB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Food Interactions Not Available
Targets

1. Squalene monooxygenase

Pharmacological action: yes
Actions: inhibitor

Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway

Organism class: human
UniProt ID: Q14534 Link_out
Gene: SQLE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mukherjee PK, Leidich SD, Isham N, Leitner I, Ryder NS, Ghannoum MA: Clinical Trichophyton rubrum strain exhibiting primary resistance to terbinafine. Antimicrob Agents Chemother. 2003 Jan;47(1):82-6. Pubmed
  2. Gao PH, Cao YB, Xu Z, Zhang JD, Zhang WN, Wang Y, Gu J, Cao YY, Li RY, Jia XM, Jiang YY: In vitro antifungal activity of ZJ-522, a new triazole restructured from fluconazole and butenafine, against clinically important fungi in comparison with fluconazole and butenafine. Biol Pharm Bull. 2005 Aug;28(8):1414-7. Pubmed
  3. Singal A: Butenafine and superficial mycoses: current status. Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):999-1005. Pubmed
  4. Ramam M, Prasad HR, Manchanda Y, Khaitan BK, Banerjee U, Mukhopadhyaya A, Shetty R, Gogtay JA: Randomised controlled trial of topical butenafine in tinea cruris and tinea corporis. Indian J Dermatol Venereol Leprol. 2003 Mar-Apr;69(2):154-8. Pubmed
  5. Iwatani W, Arika T, Yamaguchi H: Two mechanisms of butenafine action in Candida albicans. Antimicrob Agents Chemother. 1993 Apr;37(4):785-8. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:08

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.