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Identification
NameNaftifine
Accession NumberDB00735  (APRD01131)
TypeSmall Molecule
GroupsApproved
Description

Naftifine is a synthetic, broad spectrum, antifungal agent and allylamine derivative for the topical treatment of tinea pedis, tinea cruris, and tinea corporis caused by the organisms Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans and Epidermophyton floccosum.

Structure
Thumb
Synonyms
Naftifin
Naftifina
Naftifine
Naftifinum
Naftin
External Identifiers
  • AW 105 843
  • SN 105843
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Naftifine Hydrochloridecream1 mg/gtopicalRenaissance Pharma, Inc2015-06-01Not applicableUs
Naftifine Hydrochloridecream20 mg/gtopicalRenaissance Pharma, Inc2016-02-01Not applicableUs
Naftincream10 mg/2gtopicalMerz Pharmaceuticals, LLC2012-03-01Not applicableUs
Naftincream10 mg/gtopicalPhysicians Total Care, Inc.2010-06-17Not applicableUs
Naftingel10 mg/gtopicalPhysicians Total Care, Inc.2005-12-29Not applicableUs
Naftingel10 mg/gtopicalMerz Pharmaceuticals, LLC1990-10-01Not applicableUs
Naftincream10 mg/gtopicalMerz Pharmaceuticals, LLC1998-06-01Not applicableUs
Naftingel2 g/100gtopicalMerz Pharmaceuticals, LLC2013-09-01Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Naftifine Hydrochloridecream20 mg/gtopicalTaro Pharmaceuticals U.S.A., Inc.2016-01-06Not applicableUs
Approved Over the Counter Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Naftin Crm 1%cream1 %topicalAllergan Herbert Skin Care Division Of Allergan Inc.1993-12-312011-08-04Canada
Naftin Gel 1%gel1 %topicalAllergan Herbert Skin Care Division Of Allergan Inc.1993-12-312011-08-04Canada
Unapproved/Other Products Not Available
International Brands
NameCompany
A MeiShou Chan
AncentYuan Chou
ExoderilSandoz
MicosonaBayer
NaftifinaAntibiotice
SuadianSandoz
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Naftifine Hydrochloride
Thumb
  • InChI Key: OLUNPKFOFGZHRT-YGCVIUNWSA-N
  • Monoisotopic Mass: 323.144077416
  • Average Mass: 323.859
DBSALT000677
Categories
UNII4FB1TON47A
CAS number65472-88-0
WeightAverage: 287.3981
Monoisotopic: 287.167399677
Chemical FormulaC21H21N
InChI KeyInChIKey=OZGNYLLQHRPOBR-DHZHZOJOSA-N
InChI
InChI=1S/C21H21N/c1-22(16-8-11-18-9-3-2-4-10-18)17-20-14-7-13-19-12-5-6-15-21(19)20/h2-15H,16-17H2,1H3/b11-8+
IUPAC Name
methyl(naphthalen-1-ylmethyl)(3-phenylprop-2-en-1-yl)amine
SMILES
CN(CC=CC1=CC=CC=C1)CC1=CC=CC2=CC=CC=C12
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
  • Phenylpropene
  • Styrene
  • Benzylamine
  • Aralkylamine
  • Monocyclic benzene moiety
  • Tertiary aliphatic amine
  • Tertiary amine
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationFor the topical treatment of tinea pedis, tinea cruris, and tinea corporis caused by the organisms Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans and Epidermophyton floccosum.
PharmacodynamicsNaftifine is a synthetic, broad spectrum, antifungal agent and allylamine derivative. The following in vitro data are available, but their clinical significance is unknown. Naftifine has been shown to exhibit fungicidal activity in vitro against a broad spectrum of organisms including Trichophyton rubrum, Trichophyton mentagrophytes, Trichophyton tonsurans, Epidermophyton floccosum, and Microsporum canis, Microsporum audouini, and Microsporum gypseum; and fungistatic activity against Candida species including Candida albicans. However it is only used to treat the organisms listed in the indications.
Mechanism of actionAlthough the exact mechanism of action against fungi is not known, naftifine appears to interfere with sterol biosynthesis by inhibiting the enzyme squalene 2,3-epoxidase. This inhibition of enzyme activity results in decreased amounts of sterols, especially ergosterol, and a corresponding accumulation of squalene in the cells.
Related Articles
AbsorptionFollowing single topical applications of 3H-labeled naftifine gel 1% to the skin of healthy subjects, up to 4.2% of the applied dose was absorbed.
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNaftifine and/or its metabolites are excreted via the urine and feces with a half-life of approximately two to three days.
Half lifeApproximately 2 to 3 days following topical administration.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Yeast and other fungi
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9968
Blood Brain Barrier+0.9713
Caco-2 permeable+0.812
P-glycoprotein substrateSubstrate0.525
P-glycoprotein inhibitor INon-inhibitor0.8649
P-glycoprotein inhibitor IIInhibitor0.6605
Renal organic cation transporterInhibitor0.5834
CYP450 2C9 substrateNon-substrate0.7661
CYP450 2D6 substrateNon-substrate0.829
CYP450 3A4 substrateNon-substrate0.5646
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8932
CYP450 2C19 inhibitorInhibitor0.8993
CYP450 3A4 inhibitorNon-inhibitor0.876
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6083
Ames testNon AMES toxic0.5561
CarcinogenicityNon-carcinogens0.6525
BiodegradationNot ready biodegradable0.9926
Rat acute toxicity2.5407 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.6159
hERG inhibition (predictor II)Non-inhibitor0.6593
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Merz pharmaceuticals llc
Packagers
Dosage forms
FormRouteStrength
Creamtopical1 mg/g
Creamtopical20 mg/g
Creamtopical10 mg/2g
Creamtopical10 mg/g
Geltopical10 mg/g
Geltopical2 g/100g
Creamtopical1 %
Geltopical1 %
Prices
Unit descriptionCostUnit
Naftin 1% Gel 90 gm Tube290.08USD tube
Naftin 1% Cream 90 gm Tube248.26USD tube
Naftin 1% Gel 60 gm Tube208.5USD tube
Naftin 1% Cream 60 gm Tube183.77USD tube
Naftin 1% Gel 40 gm Tube147.0USD tube
Naftin 1% Cream 30 gm Tube101.62USD tube
Naftin pump 1% cream3.2USD g
Naftin 1% cream2.45USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8778365 No2013-01-312033-01-31Us
US9161914 No2013-01-312033-01-31Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP5.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000229 mg/mLALOGPS
logP4.96ALOGPS
logP5.24ChemAxon
logS-6.1ALOGPS
pKa (Strongest Basic)9.08ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area3.24 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity95.98 m3·mol-1ChemAxon
Polarizability34.05 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

DrugSyn.org

US4282251
General ReferencesNot Available
External Links
ATC CodesD01AE22
AHFS Codes
  • 84:04.08.04
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (14.2 KB)
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot Available

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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
  2. Favre B, Ryder NS: Characterization of squalene epoxidase activity from the dermatophyte Trichophyton rubrum and its inhibition by terbinafine and other antimycotic agents. Antimicrob Agents Chemother. 1996 Feb;40(2):443-7. [PubMed:8834895 ]
  3. Vanden Bossche H, Marichal P: Mode of action of anti-Candida drugs: focus on terconazole and other ergosterol biosynthesis inhibitors. Am J Obstet Gynecol. 1991 Oct;165(4 Pt 2):1193-9. [PubMed:1951574 ]
  4. 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 ]
  5. Ryder NS, Dupont MC: Inhibition of squalene epoxidase by allylamine antimycotic compounds. A comparative study of the fungal and mammalian enzymes. Biochem J. 1985 Sep 15;230(3):765-70. [PubMed:3877503 ]
  6. Ryder NS, Frank I: Interaction of terbinafine with human serum and serum proteins. J Med Vet Mycol. 1992;30(6):451-60. [PubMed:1287164 ]
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Drug created on June 13, 2005 07:24 / Updated on July 28, 2016 01:52