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Identification
NameButenafine
Accession NumberDB01091  (APRD00833)
TypeSmall Molecule
GroupsApproved
DescriptionButenafine 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
Synonyms
(4-Tert-butyl-benzyl)-methyl-naphthalen-1-ylmethyl-amine
(4-Tert-butylphenyl)-N-methyl-N-(naphthalen-1-ylmethyl)methanamine
4-Tert-butylbenzyl(methyl)(1-naphthalenemethyl)amine
Butenafina
Butenafine
Butenafinum
N-(P-Tert-butylbenzyl)-N-methyl-1-naphthalenemethylamine
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
MentaxCream10 mg/gTopicalMylan Pharmaceuticals Inc.1996-12-31Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Dr. Scholl's Athlete's Foot CreamCream1 %TopicalPenederm Inc.1997-09-102006-10-09Canada
Dr. Scholl's Athlete's Foot CreamCream1 %TopicalSchering Plough Healthcare Products Canada, A Division Of Schering Canada Inc.2000-04-302005-08-05Canada
Lotrimin Ultra AntifungalCream10 mg/gTopicalMSD Consumer Care, Inc.1993-09-23Not applicableUs
Lotrimin Ultra Athletes FootCream1 g/100gTopicalBayer HealthCare LLC2002-02-22Not applicableUs
Lotrimin Ultra Jock ItchCream1 g/100gTopicalBayer HealthCare LLC2002-02-22Not applicableUs
Lotrimin Ultra Jock Itch AntifungalCream10 mg/gTopicalMSD Consumer Care, Inc.1993-09-23Not applicableUs
Tinactin Once-A-day CreamCream1 %TopicalBayer Inc Consumer CareNot applicableNot applicableCanada
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Butenafine Hydrochloride
101827-46-7
Thumb
  • InChI Key: LJBSAUIFGPSHCN-UHFFFAOYSA-N
  • Monoisotopic Mass: 353.191027608
  • Average Mass: 353.928
DBSALT000245
Categories
UNII91Y494NL0X
CAS number101828-21-1
WeightAverage: 317.4672
Monoisotopic: 317.214349869
Chemical FormulaC23H27N
InChI KeyABJKWBDEJIDSJZ-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
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=CC=CC=C12
Pharmacology
IndicationFor 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.
Structured Indications
PharmacodynamicsButenafine 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 actionAlthough 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.
TargetKindPharmacological actionActionsOrganismUniProt ID
Squalene monooxygenaseProteinyes
inhibitor
HumanQ14534 details
Related Articles
AbsorptionThe total amount absorbed through the skin into the systemic circulation has not been quantified.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

The primary metabolite in urine was formed through hydroxylation at the terminal t-butyl side-chain.

Route of eliminationNot Available
Half lifeFollowing 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.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Fungi
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AmlodipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Amlodipine.Approved
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Butenafine.Approved, Investigational
AmrinoneThe risk or severity of adverse effects can be increased when Butenafine is combined with Amrinone.Approved
AzelnidipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Azelnidipine.Approved
AzimilideThe risk or severity of adverse effects can be increased when Butenafine is combined with Azimilide.Investigational
BarnidipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Barnidipine.Approved
BenidipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Benidipine.Approved
BepridilThe risk or severity of adverse effects can be increased when Butenafine is combined with Bepridil.Approved, Withdrawn
BuspironeThe metabolism of Buspirone can be decreased when combined with Butenafine.Approved, Investigational
BusulfanThe serum concentration of Busulfan can be increased when it is combined with Butenafine.Approved, Investigational
CaiThe risk or severity of adverse effects can be increased when Butenafine is combined with Cai.Investigational
CilnidipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Cilnidipine.Approved
CinnarizineThe risk or severity of adverse effects can be increased when Butenafine is combined with Cinnarizine.Approved
CisaprideThe serum concentration of Cisapride can be increased when it is combined with Butenafine.Approved, Investigational, Withdrawn
ClevidipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Clevidipine.Approved
ConivaptanThe metabolism of Conivaptan can be decreased when combined with Butenafine.Approved, Investigational
CyclosporineThe metabolism of Cyclosporine can be decreased when combined with Butenafine.Approved, Investigational, Vet Approved
DarodipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Darodipine.Experimental
DidanosineDidanosine can cause a decrease in the absorption of Butenafine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
DiltiazemThe risk or severity of adverse effects can be increased when Butenafine is combined with Diltiazem.Approved
DocetaxelThe metabolism of Docetaxel can be decreased when combined with Butenafine.Approved, Investigational
DofetilideThe metabolism of Dofetilide can be decreased when combined with Butenafine.Approved
DotarizineThe risk or severity of adverse effects can be increased when Butenafine is combined with Dotarizine.Investigational
EfonidipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Efonidipine.Approved
EperisoneThe risk or severity of adverse effects can be increased when Butenafine is combined with Eperisone.Approved, Investigational
EtravirineThe serum concentration of Etravirine can be increased when it is combined with Butenafine.Approved
FelodipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Felodipine.Approved, Investigational
FendilineThe risk or severity of adverse effects can be increased when Butenafine is combined with Fendiline.Withdrawn
FlunarizineThe risk or severity of adverse effects can be increased when Butenafine is combined with Flunarizine.Approved
FosphenytoinThe serum concentration of Butenafine can be decreased when it is combined with Fosphenytoin.Approved
GabapentinThe risk or severity of adverse effects can be increased when Butenafine is combined with Gabapentin.Approved, Investigational
GallopamilThe risk or severity of adverse effects can be increased when Butenafine is combined with Gallopamil.Investigational
IsradipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Isradipine.Approved
LacidipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Lacidipine.Approved
LamotrigineThe risk or severity of adverse effects can be increased when Butenafine is combined with Lamotrigine.Approved, Investigational
LercanidipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Lercanidipine.Approved, Investigational
LosartanThe metabolism of Losartan can be decreased when combined with Butenafine.Approved
Magnesium SulfateThe risk or severity of adverse effects can be increased when Butenafine is combined with Magnesium Sulfate.Approved, Vet Approved
ManidipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Manidipine.Approved
MibefradilThe risk or severity of adverse effects can be increased when Butenafine is combined with Mibefradil.Withdrawn
NaftopidilThe risk or severity of adverse effects can be increased when Butenafine is combined with Naftopidil.Investigational
NicardipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Nicardipine.Approved
NifedipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Nifedipine.Approved
NiguldipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Niguldipine.Experimental
NiludipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Niludipine.Experimental
NilvadipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Nilvadipine.Approved
NimesulideThe risk or severity of adverse effects can be increased when Butenafine is combined with Nimesulide.Approved, Withdrawn
NimodipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Nimodipine.Approved
NisoldipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Nisoldipine.Approved
NitrendipineThe risk or severity of adverse effects can be increased when Butenafine is combined with Nitrendipine.Approved
PerhexilineThe risk or severity of adverse effects can be increased when Butenafine is combined with Perhexiline.Approved
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Butenafine.Approved, Vet Approved
PimozideButenafine may increase the arrhythmogenic activities of Pimozide.Approved
PinaveriumThe risk or severity of adverse effects can be increased when Butenafine is combined with Pinaverium.Approved
PregabalinThe risk or severity of adverse effects can be increased when Butenafine is combined with Pregabalin.Approved, Illicit, Investigational
PrenylamineThe risk or severity of adverse effects can be increased when Butenafine is combined with Prenylamine.Withdrawn
ProgesteroneThe therapeutic efficacy of Progesterone can be decreased when used in combination with Butenafine.Approved, Vet Approved
QuinidineThe metabolism of Quinidine can be decreased when combined with Butenafine.Approved
RanolazineThe metabolism of Ranolazine can be decreased when combined with Butenafine.Approved, Investigational
RifabutinThe serum concentration of Rifabutin can be increased when it is combined with Butenafine.Approved
RifampicinThe serum concentration of Rifampicin can be increased when it is combined with Butenafine.Approved
RifapentineThe serum concentration of Rifapentine can be increased when it is combined with Butenafine.Approved
RisedronateThe risk or severity of adverse effects can be increased when Butenafine is combined with Risedronate.Approved, Investigational
SolifenacinThe metabolism of Solifenacin can be decreased when combined with Butenafine.Approved
SucralfateSucralfate can cause a decrease in the absorption of Butenafine resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
SunitinibThe metabolism of Sunitinib can be decreased when combined with Butenafine.Approved, Investigational
TacrolimusThe metabolism of Tacrolimus can be decreased when combined with Butenafine.Approved, Investigational
Tolfenamic AcidThe risk or severity of adverse effects can be increased when Butenafine is combined with Tolfenamic Acid.Approved
TranilastThe risk or severity of adverse effects can be increased when Butenafine is combined with Tranilast.Approved, Investigational
VerapamilThe risk or severity of adverse effects can be increased when Butenafine is combined with Verapamil.Approved
VinpocetineThe risk or severity of adverse effects can be increased when Butenafine is combined with Vinpocetine.Investigational
XylometazolineThe risk or severity of adverse effects can be increased when Butenafine is combined with Xylometazoline.Approved
ZiconotideThe risk or severity of adverse effects can be increased when Butenafine is combined with Ziconotide.Approved
ZolpidemThe serum concentration of Zolpidem can be increased when it is combined with Butenafine.Approved
Food InteractionsNot Available
References
Synthesis Reference

DrugSyn.org

US5021458
General References
  1. McNeely W, Spencer CM: Butenafine. Drugs. 1998 Mar;55(3):405-12; discussion 413. [PubMed:9530545 ]
  2. Singal A: Butenafine and superficial mycoses: current status. Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):999-1005. doi: 10.1517/17425255.4.7.999 . [PubMed:18624686 ]
  3. Gupta AK: Butenafine: an update of its use in superficial mycoses. Skin Therapy Lett. 2002 Sep;7(7):1-2, 5. [PubMed:12432425 ]
  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:11709307 ]
  5. Syed TA, Maibach HI: Butenafine hydrochloride: for the treatment of interdigital tinea pedis. Expert Opin Pharmacother. 2000 Mar;1(3):467-73. [PubMed:11249531 ]
  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:9646136 ]
  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:8494375 ]
External Links
ATC CodesD01AE23
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (1.39 MB)
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9904
Blood Brain Barrier+0.9514
Caco-2 permeable+0.7822
P-glycoprotein substrateSubstrate0.5855
P-glycoprotein inhibitor INon-inhibitor0.8215
P-glycoprotein inhibitor IIInhibitor0.7052
Renal organic cation transporterNon-inhibitor0.5078
CYP450 2C9 substrateNon-substrate0.8124
CYP450 2D6 substrateNon-substrate0.8686
CYP450 3A4 substrateSubstrate0.6225
CYP450 1A2 substrateNon-inhibitor0.6056
CYP450 2C9 inhibitorNon-inhibitor0.9401
CYP450 2D6 inhibitorInhibitor0.8189
CYP450 2C19 inhibitorNon-inhibitor0.666
CYP450 3A4 inhibitorNon-inhibitor0.7581
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6169
Ames testNon AMES toxic0.9008
CarcinogenicityCarcinogens 0.5115
BiodegradationNot ready biodegradable0.9972
Rat acute toxicity2.2204 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8911
hERG inhibition (predictor II)Inhibitor0.5849
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
CreamTopical1 %
CreamTopical1 g/100g
CreamTopical10 mg/g
Prices
Unit descriptionCostUnit
Mentax 1% Cream 30 gm Tube124.7USD tube
Mentax 1% Cream 15 gm Tube50.99USD tube
Mentax 1% cream4.0USD g
Lotrimin ultra 1% cream0.68USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5021458 No1993-10-182010-10-18Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
water solubilitySlightly soluble (HCl salt)Not Available
logP6.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility7.56e-05 mg/mLALOGPS
logP5.85ALOGPS
logP6.17ChemAxon
logS-6.6ALOGPS
pKa (Strongest Basic)9.23ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity104.33 m3·mol-1ChemAxon
Polarizability38.41 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as naphthalenes. These are compounds containing a naphthalene moiety, which consists of two fused benzene rings.
KingdomOrganic compounds
Super ClassBenzenoids
ClassNaphthalenes
Sub ClassNot Available
Direct ParentNaphthalenes
Alternative Parents
Substituents
  • Naphthalene
  • Phenylpropane
  • Phenylmethylamine
  • Benzylamine
  • Aralkylamine
  • Monocyclic benzene moiety
  • Tertiary aliphatic amine
  • Tertiary amine
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Squalene monooxygenase activity
Specific Function:
Catalyzes the first oxygenation step in sterol biosynthesis and is suggested to be one of the rate-limiting enzymes in this pathway.
Gene Name:
SQLE
Uniprot ID:
Q14534
Molecular Weight:
63922.505 Da
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:12499173 ]
  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:16079485 ]
  3. Singal A: Butenafine and superficial mycoses: current status. Expert Opin Drug Metab Toxicol. 2008 Jul;4(7):999-1005. doi: 10.1517/17425255.4.7.999 . [PubMed:18624686 ]
  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:17642865 ]
  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:8494375 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23