Identification

Name
Efinaconazole
Accession Number
DB09040
Type
Small Molecule
Groups
Approved
Description

Efinaconazole is a 14 alpha-demethylase inhibitor indicated in the treatment of fungal infection of the nail, known as onychomycosis. It was approved for use in Canada and the USA in 2014 and is marketed by Valeant Pharmaceuticals North America LLC under the name Jublia.

Structure
Thumb
Synonyms
  • (2R,3R)-2-(2,4-Difluorophenyl)-3-(4-methylene-1-piperidinyl)-1-(1H-1,2,4-triazol-1-yl)-2-butanol
External IDs
IDP 108 / IDP-108 / IDP108 / KP 103 / KP-103
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
JubliaSolution10 %TopicalValeant Canada Lp Valeant Canada S.E.C.2014-07-21Not applicableCanada
JubliaSolution100 mg/1mLTopicalValeant Pharmaceuticals North America2014-06-06Not applicableUs
Categories
UNII
J82SB7FXWB
CAS number
164650-44-6
Weight
Average: 348.398
Monoisotopic: 348.17616767
Chemical Formula
C18H22F2N4O
InChI Key
NFEZZTICAUWDHU-RDTXWAMCSA-N
InChI
InChI=1S/C18H22F2N4O/c1-13-5-7-23(8-6-13)14(2)18(25,10-24-12-21-11-22-24)16-4-3-15(19)9-17(16)20/h3-4,9,11-12,14,25H,1,5-8,10H2,2H3/t14-,18-/m1/s1
IUPAC Name
(2R,3R)-2-(2,4-difluorophenyl)-3-(4-methylidenepiperidin-1-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
SMILES
C[C@@H](N1CCC(=C)CC1)[C@](O)(CN1C=NC=N1)C1=C(F)C=C(F)C=C1

Pharmacology

Indication

Indicated in the treatment of fungal infection of the nail, known as onychomycosis.

Associated Conditions
Pharmacodynamics

mean ± SD plasma Cmax on Day 28 of treatment: 0.67 ± 0.37 ng/mL. mean ± SD AUC was 12.15 ± 6.91 ng*h/mL.

Mechanism of action

Efinaconazole is an azole antifungal. Efinaconazole inhibits fungal lanosterol 14α-demethylase involved in the biosynthesis of ergosterol, a constituent of fungal cell membranes.

TargetActionsOrganism
ALanosterol 14-alpha demethylase
inhibitor
Yeast
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life

29.9 hours in healthy patients.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Candida albicans and other yeasts
  • Yeast and other Trichophyton or Microsporum fungi
  • Dermatophytic fungi including Trichophyton, Microsporum and Epidermophyton
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AgmatineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Agmatine.
AmiodaroneThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Amiodarone.
AmlodipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Amlodipine.
Amphotericin BThe therapeutic efficacy of Amphotericin B can be decreased when used in combination with Efinaconazole.
AmrinoneThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Amrinone.
AranidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Aranidipine.
AtorvastatinThe risk or severity of myopathy can be increased when Efinaconazole is combined with Atorvastatin.
AzelnidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Azelnidipine.
AzimilideThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Azimilide.
BarnidipineThe therapeutic efficacy of Efinaconazole can be increased when used in combination with Barnidipine.
Food Interactions
Not Available

References

General References
  1. Patel T, Dhillon S: Efinaconazole: first global approval. Drugs. 2013 Nov;73(17):1977-83. doi: 10.1007/s40265-013-0152-x. [PubMed:24249649]
External Links
KEGG Drug
D10021
PubChem Compound
489181
PubChem Substance
310264988
ChemSpider
428538
ChEBI
82718
ChEMBL
CHEMBL2103877
Drugs.com
Drugs.com Drug Page
Wikipedia
Efinaconazole
ATC Codes
D01AC19 — Efinaconazole
AHFS Codes
  • 84:04.08.08 — Azoles
FDA label
Download (330 KB)
MSDS
Download (226 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentOnychomycosis2
4Active Not RecruitingTreatmentDermatophytosis / Onychomycosis1
4Active Not RecruitingTreatmentOnychomycosis1
4Active Not RecruitingTreatmentOnychomycosis of Toenail1
4RecruitingTreatmentMild to Moderate Onychomycosis Due to Dermatophyte1
Not AvailableRecruitingNot AvailableDistal Lateral Subungual Onychomycosis (DLSO)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionTopical10 %
SolutionTopical100 mg/1mL
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US7214506No2001-10-052021-10-05Us
US8039494No2010-07-082030-07-08Us
US8486978No2010-10-242030-10-24Us
US9302009No2010-10-242030-10-24Us
US9662394No2014-10-022034-10-02Us
US9566272No2008-01-032028-01-03Us
US9861698No2010-07-082030-07-08Us
US9877955No2008-01-032028-01-03Us

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.61 mg/mLALOGPS
logP1.49ALOGPS
logP2.24ChemAxon
logS-2.8ALOGPS
pKa (Strongest Acidic)12.7ChemAxon
pKa (Strongest Basic)7.45ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area54.18 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity103.94 m3·mol-1ChemAxon
Polarizability34.48 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

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

Taxonomy

Description
This compound belongs to the class of organic compounds known as amphetamines and derivatives. These are organic compounds containing or derived from 1-phenylpropan-2-amine.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenethylamines
Direct Parent
Amphetamines and derivatives
Alternative Parents
Phenylpropanes / Fluorobenzenes / Aralkylamines / Piperidines / Aryl fluorides / Triazoles / Tertiary alcohols / Heteroaromatic compounds / Trialkylamines / 1,2-aminoalcohols
show 5 more
Substituents
Amphetamine or derivatives / Phenylpropane / Fluorobenzene / Halobenzene / Aralkylamine / Aryl fluoride / Aryl halide / Piperidine / Azole / Heteroaromatic compound
show 19 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
piperidines, organofluorine compound, tertiary alcohol, tertiary amino compound, triazole antifungal drug, conazole antifungal drug, olefinic compound (CHEBI:82718)

Targets

Kind
Protein
Organism
Yeast
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sterol 14-demethylase activity
Specific Function
Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol (By similarity).
Gene Name
ERG11
Uniprot ID
P50859
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
61304.95 Da
References
  1. Patel T, Dhillon S: Efinaconazole: first global approval. Drugs. 2013 Nov;73(17):1977-83. doi: 10.1007/s40265-013-0152-x. [PubMed:24249649]

Drug created on April 21, 2015 10:37 / Updated on September 23, 2018 19:37