Identification

Name
Naftifine
Accession Number
DB00735  (APRD01131)
Type
Small Molecule
Groups
Approved
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
External IDs
AW 105 843 / SN 105843
Product Ingredients
IngredientUNIICASInChI Key
Naftifine Hydrochloride25UR9N904165473-14-5OLUNPKFOFGZHRT-YGCVIUNWSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Naftifine HydrochlorideCream20 mg/1gTopicalRenaissance Pharma, Inc.2016-02-01Not applicableUs
Naftifine HydrochlorideCream1 mg/1gTopicalRenaissance Pharma, Inc.2015-06-01Not applicableUs
NaftinGel10 mg/1gTopicalPhysicians Total Care, Inc.2005-12-29Not applicableUs
NaftinCream10 mg/1gTopicalDPT Laboratories, Ltd.2006-01-252010-01-05Us
NaftinCream10 mg/2gTopicalSebela Pharmaceuticals Inc.2018-02-28Not applicableUs
NaftinGel2 g/100gTopicalMerz Pharmaceuticals2013-09-012016-12-01Us
NaftinCream10 mg/1gTopicalMerz Pharmaceuticals1998-06-01Not applicableUs
NaftinGel10 mg/1gTopicalSebela Pharmaceuticals Inc.2018-01-22Not applicableUs
NaftinGel10 mg/1gTopicalMerz Pharmaceuticals1990-10-012016-12-01Us
NaftinCream10 mg/1gTopicalPhysicians Total Care, Inc.2010-06-17Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Naftifine HydrochlorideCream20 mg/1gTopicalImpax Generics2017-05-10Not applicableUs
Naftifine HydrochlorideCream10 mg/1gTopicalTaro Pharmaceuticals U.S.A., Inc.2016-09-08Not applicableUs
Naftifine HydrochlorideCream20 mg/1gTopicalTaro Pharmaceuticals U.S.A., Inc.2016-01-06Not applicableUs
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
International/Other Brands
A Mei (Shou Chan) / Ancent (Yuan Chou) / Exoderil (Sandoz) / Micosona (Bayer) / Naftifina (Antibiotice) / Naftin / Suadian (Sandoz)
Categories
UNII
4FB1TON47A
CAS number
65472-88-0
Weight
Average: 287.3981
Monoisotopic: 287.167399677
Chemical Formula
C21H21N
InChI Key
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

Pharmacology

Indication

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.

Associated Conditions
Pharmacodynamics

Naftifine 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 action

Although 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.

TargetActionsOrganism
ASqualene monooxygenase
inhibitor
Human
Absorption

Following 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 distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Naftifine and/or its metabolites are excreted via the urine and feces with a half-life of approximately two to three days.

Half life

Approximately 2 to 3 days following topical administration.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Yeast and other fungi
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

Synthesis Reference
US4282251
General References
Not Available
External Links
KEGG Compound
C08071
PubChem Compound
73342
PubChem Substance
46504777
ChemSpider
43344
BindingDB
50170647
ChEBI
7451
ChEMBL
CHEMBL626
Therapeutic Targets Database
DAP000752
PharmGKB
PA164748617
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Naftifine
ATC Codes
D01AE22 — Naftifine
MSDS
Download (14.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentTinea Pedis3
3CompletedTreatmentTinea Cruris1
3CompletedTreatmentTinea Pedis4
4CompletedTreatmentTinea Corporis2
4CompletedTreatmentTinea Cruris / Tinea Pedis1

Pharmacoeconomics

Manufacturers
  • Merz pharmaceuticals llc
Packagers
  • DPT Laboratories Ltd.
  • Merz Pharmaceuticals LLC
  • Physicians Total Care Inc.
Dosage forms
FormRouteStrength
CreamTopical1 mg/1g
CreamTopical20 mg/1g
CreamTopical10 mg/2g
CreamTopical10 mg/1g
GelTopical10 mg/1g
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)
US9161914No2013-01-312033-01-31Us
US8778365No2013-01-312033-01-31Us

Properties

State
Solid
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 FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014r-0940000000-736e1306e0a1b21a69e5
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-1a47528b60d38f7230ea
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-db364fa78b21edf4eb3a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-0900000000-43af6cd3170ea07037e0
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014l-0900000000-2a982f932855fa74205f
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014l-1900000000-6aded55bd308a6ddc1e8
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014l-4900000000-382482d4ffa5075b4d29
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-8900000000-ad11e6913754f48ce01d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-014i-9400000000-52e2c99bae16686c15b3

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Naphthalenes
Sub Class
Not Available
Direct Parent
Naphthalenes
Alternative Parents
Styrenes / Aralkylamines / Trialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Naphthalene / Styrene / Aralkylamine / Monocyclic benzene moiety / Tertiary aliphatic amine / Tertiary amine / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative / Organonitrogen compound
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
Not 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
Uniprot Name
Squalene monooxygenase
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]

Drug created on June 13, 2005 07:24 / Updated on October 01, 2018 16:28