Identification

Name
Voriconazole
Accession Number
DB00582  (APRD00543)
Type
Small Molecule
Groups
Approved, Investigational
Description

Voriconazole (Vfend®, Pfizer) is a triazole antifungal medication used to treat serious fungal infections. It is used to treat invasive fungal infections that are generally seen in patients who are immunocompromised. These include invasive candidiasis, invasive aspergillosis, and emerging fungal infections.

Structure
Thumb
Synonyms
  • (AlphaR,betas)-alpha-(2,4-difluorophenyl)-5-fluoro-beta-methyl-alpha(1H-1,2,4-triazol-1-ylmethyl)-4-pyrimidineethanol
  • (R-(R*,s*))-alpha-(2,4-difluorophenyl)-5-fluoro-beta-methyl-alpha-(1H-1,2,4-triazol-1-ylmethyl)-4-pyrimidineethanol
  • VCZ
  • Voriconazol
  • Voriconazolum
External IDs
UK-109,496
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Sandoz VoriconazoleTablet50 mgOralSandoz Canada Incorporated2014-04-02Not applicableCanada
Sandoz VoriconazoleTablet200 mgOralSandoz Canada Incorporated2014-04-02Not applicableCanada
VfendTablet200 mgOralPfizer2002-03-19Not applicableEu
VfendInjection, powder, lyophilized, for solution10 mg/1mLIntravenousRoerig2012-10-24Not applicableUs
VfendTablet50 mgOralPfizer2002-03-19Not applicableEu
VfendPowder, for suspension3 gOralPfizer2008-07-17Not applicableCanada
VfendTablet50 mgOralPfizer2002-03-19Not applicableEu
VfendTablet50 mgOralPfizer2004-11-12Not applicableCanada
VfendTablet200 mgOralPfizer2002-03-19Not applicableEu
VfendTablet200 mgOralPfizer2002-03-19Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ach-voriconazoleTablet50 mgOralAccord Healthcare LimitedNot applicableNot applicableCanada
Apo-voriconazoleTablet200 mgOralApotex Corporation2014-04-14Not applicableCanada
Apo-voriconazoleTablet50 mgOralApotex Corporation2014-04-14Not applicableCanada
Auro-voriconazoleTablet50 mgOralAuro Pharma IncNot applicableNot applicableCanada
Auro-voriconazoleTablet200 mgOralAuro Pharma IncNot applicableNot applicableCanada
Mylan-voriconazoleTablet50 mgOralMylan PharmaceuticalsNot applicableNot applicableCanada
Mylan-voriconazoleTablet200 mgOralMylan PharmaceuticalsNot applicableNot applicableCanada
PMS-voriconazolePowder, for solution200 mgIntravenousPharmascience IncNot applicableNot applicableCanada
Teva-voriconazoleTablet50 mgOralTeva2014-03-31Not applicableCanada
Teva-voriconazoleTablet200 mgOralTeva2014-03-31Not applicableCanada
International/Other Brands
Vfend
Categories
UNII
JFU09I87TR
CAS number
137234-62-9
Weight
Average: 349.3105
Monoisotopic: 349.11504471
Chemical Formula
C16H14F3N5O
InChI Key
BCEHBSKCWLPMDN-MGPLVRAMSA-N
InChI
InChI=1S/C16H14F3N5O/c1-10(15-14(19)5-20-7-22-15)16(25,6-24-9-21-8-23-24)12-3-2-11(17)4-13(12)18/h2-5,7-10,25H,6H2,1H3/t10-,16+/m0/s1
IUPAC Name
(2R,3S)-2-(2,4-difluorophenyl)-3-(5-fluoropyrimidin-4-yl)-1-(1H-1,2,4-triazol-1-yl)butan-2-ol
SMILES
C[C@@H](C1=NC=NC=C1F)[C@](O)(CN1C=NC=N1)C1=C(F)C=C(F)C=C1

Pharmacology

Indication

For the treatment of esophageal candidiasis, invasive pulmonary aspergillosis, and serious fungal infections caused by Scedosporium apiospermum and Fusarium spp.

Associated Conditions
Pharmacodynamics

Voriconazole is a triazole antifungal agent indicated for use in the treatment of fungal infections including invasive aspergillosis, esophageal candidiasis, and serious fungal infections caused by Scedosporium apiospermum (asexual form of Pseudallescheria boydii) and Fusarium spp. including Fusarium solani. Fungal plasma membranes are similar to mammalian plasma membranes, differing in having the nonpolar sterol ergosterol, rather than cholesterol, as the principal sterol. Membrane sterols such as ergosterol provide structure, modulation of membrane fluidity, and possibly control of some physiologic events. Voriconazole effects the formation of the fungal plasma membrane by indirectly inhibiting the biosynthesis of ergosterol. This results in plasma membrane permeability changes and inhibition of growth.

Mechanism of action

Voriconazole binds and inhibits ergosterol synthesis by inhibiting CYP450-dependent 14-alpha sterol demethylase. The inhibition of 14-alpha sterol demethylase results in a depletion of ergosterol in fungal cell membrane.

TargetActionsOrganism
ALanosterol 14-alpha demethylase
antagonist
inhibitor
Yeast
Absorption

The oral bioavailability is estimated to be 96% (CV 13%).

Volume of distribution
  • 4.6 L/kg
Protein binding

58%

Metabolism

Hepatic. The major metabolite of voriconazole is the N-oxide, which accounts for 72% of the circulating radiolabelled metabolites in plasma. Since this metabolite has minimal antifungal activity, it does not contribute to the overall efficacy of voriconazole.

Route of elimination

Voriconazole is eliminated via hepatic metabolism with less than 2% of the dose excreted unchanged in the urine.

Half life
Not Available
Clearance
Not Available
Toxicity

The minimum lethal oral dose in mice and rats was 300 mg/kg (equivalent to 4 and 7 times the recommended maintenance dose (RMD), based on body surface area). At this dose, clinical signs observed in both mice and rats included salivation, mydriasis, titubation (loss of balance while moving), depressed behavior, prostration, partially closed eyes, and dyspnea. Other signs in mice were convulsions, corneal opacification and swollen abdomen.

Affected organisms
  • Yeast and other fungi
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2C19CYPC19*17(C;T) / (T;T)C > TEffect Directly StudiedPatients with this genotype in CYP2C19 are ultra fast metabolizers and require higer doses of voriconazole to attain the therapeutic effect.Details
Cytochrome P450 2C19CYP2C19*2Not Available681G>ADirectly Studied EffectThe presence of this polymorphism in CYP2C19 is associated with poor metabolism of voriconazole.Details
Cytochrome P450 2C19CYP2C19*3Not Available636G>ADirectly Studied EffectThe presence of this polymorphism in CYP2C19 is associated with reduced or poor metabolism of voriconazole.Details
Cytochrome P450 2C19CYP2C19*2ANot Available681G>AADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*2BNot Available681G>AADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*4Not Available1A>GADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*5Not Available1297C>TADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*6Not Available395G>AADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*7Not Available19294T>AADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*22Not Available557G>C / 991A>GADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*24Not Available99C>T / 991A>G  … show all ADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails
Cytochrome P450 2C19CYP2C19*35Not Available12662A>GADR InferredPoor drug metabolizer, may lead to hepatotoxicity, visual disturbances, visual hallucinations, and other neurologic disordersDetails

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Voriconazole.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Voriconazole.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Voriconazole.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Voriconazole.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Voriconazole.
6-Deoxyerythronolide BThe metabolism of Voriconazole can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Voriconazole.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Voriconazole.
AbexinostatThe risk or severity of QTc prolongation can be increased when Voriconazole is combined with Abexinostat.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Voriconazole.
Food Interactions
Not Available

References

Synthesis Reference

Venkataraman Sundaram, Venkata Bhaskara Rao Uppala, Surya Prabhakar Akundi, Venkateswarlu Muvva, Vijayawardhan Chitta, Alekhya Donthula, Manoj Ramesh Kharkar, Surya Narayana Devarakonda, Subba Reddy Peddireddy, "Process For Preparing Voriconazole." U.S. Patent US20080194820, issued August 14, 2008.

US20080194820
General References
  1. Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene RE, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HT, Troke PF, de Pauw B: Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002 Aug 8;347(6):408-15. [PubMed:12167683]
  2. Patterson TF, Boucher HW, Herbrecht R, Denning DW, Lortholary O, Ribaud P, Rubin RH, Wingard JR, DePauw B, Schlamm HT, Troke P, Bennett JE: Strategy of following voriconazole versus amphotericin B therapy with other licensed antifungal therapy for primary treatment of invasive aspergillosis: impact of other therapies on outcome. Clin Infect Dis. 2005 Nov 15;41(10):1448-52. Epub 2005 Oct 13. [PubMed:16231256]
  3. Kullberg BJ, Sobel JD, Ruhnke M, Pappas PG, Viscoli C, Rex JH, Cleary JD, Rubinstein E, Church LW, Brown JM, Schlamm HT, Oborska IT, Hilton F, Hodges MR: Voriconazole versus a regimen of amphotericin B followed by fluconazole for candidaemia in non-neutropenic patients: a randomised non-inferiority trial. Lancet. 2005 Oct 22-28;366(9495):1435-42. [PubMed:16243088]
  4. Ally R, Schurmann D, Kreisel W, Carosi G, Aguirrebengoa K, Dupont B, Hodges M, Troke P, Romero AJ: A randomized, double-blind, double-dummy, multicenter trial of voriconazole and fluconazole in the treatment of esophageal candidiasis in immunocompromised patients. Clin Infect Dis. 2001 Nov 1;33(9):1447-54. Epub 2001 Sep 26. [PubMed:11577374]
  5. Walsh TJ, Pappas P, Winston DJ, Lazarus HM, Petersen F, Raffalli J, Yanovich S, Stiff P, Greenberg R, Donowitz G, Schuster M, Reboli A, Wingard J, Arndt C, Reinhardt J, Hadley S, Finberg R, Laverdiere M, Perfect J, Garber G, Fioritoni G, Anaissie E, Lee J: Voriconazole compared with liposomal amphotericin B for empirical antifungal therapy in patients with neutropenia and persistent fever. N Engl J Med. 2002 Jan 24;346(4):225-34. [PubMed:11807146]
External Links
Human Metabolome Database
HMDB0014720
KEGG Drug
D00578
KEGG Compound
C07622
PubChem Compound
71616
PubChem Substance
46506421
ChemSpider
64684
BindingDB
50333117
ChEBI
10023
ChEMBL
CHEMBL638
Therapeutic Targets Database
DAP001271
PharmGKB
PA10233
HET
VOR
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Voriconazole
ATC Codes
J02AC03 — Voriconazole
AHFS Codes
  • 08:14.08 — Azoles
PDB Entries
3mdt / 4uym / 4ze0 / 5hs1 / 6ay6
FDA label
Download (321 KB)
MSDS
Download (57.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Active Not RecruitingTreatmentInfections, Fungal1
1CompletedNot AvailableHealthy Volunteers1
1CompletedNot AvailableHuman Immunodeficiency Virus (HIV) Infections / Human Immunodeficiency Virus Type 1 (HIV-1)1
1CompletedNot AvailableInfections, Fungal1
1CompletedNot AvailableInvasive Aspergillosis1
1CompletedBasic ScienceBacterial Infections / Healthy Volunteers / Infections, Fungal1
1CompletedBasic ScienceHealthy Volunteers3
1CompletedTreatmentAspergillosis / Candidiasis infection / Fungal Diseases / Mycoses1
1CompletedTreatmentB-Cell Chronic Lymphocytic Leukemia1
1CompletedTreatmentGraft Versus Host Disease (GVHD) / Transplantation, Stem Cell2
1CompletedTreatmentHealthy Volunteers1
1CompletedTreatmentInfections, Fungal / Prophylaxis of Aspergillus infection / Prophylaxis of Candida Infections1
1CompletedTreatmentSystemic Mycotic Infection1
1, 2CompletedTreatmentFungal Keratitis1
1, 2CompletedTreatmentNeutropenias1
2CompletedPreventionAcute Myelogenous Leukaemia (AML) / Myelodysplastic Syndrome1
2CompletedPreventionAspergillosis, Aspergilloma1
2CompletedPreventionPharmacokinetics1
2CompletedSupportive CareInfection NOS / Unspecified Adult Solid Tumor, Protocol Specific1
2CompletedSupportive CareLeukemias / Malignant Lymphomas / Multiple Myeloma and Plasma Cell Neoplasm / Myelodysplastic Syndromes / Myelodysplastic/Myeloproliferative Neoplasms / Neuroblastomas / Neutropenias / Renal Cancers / Sarcomas1
2CompletedTreatmentCandidemia / Candidiasis infection1
2CompletedTreatmentCystic Fibrosis (CF) / Prophylaxis of Aspergillus infection1
2Not Yet RecruitingTreatmentPulmonary Invasive Aspergillosis1
2RecruitingSupportive CareHyperalgesia / Minor burns / Pain NOS / Thermal Injury1
2SuspendedTreatmentAspergillosis / Fusarium / Immunocompromised Patients1
2TerminatedSupportive CareInfection NOS / Unspecified Adult Solid Tumor, Protocol Specific1
2WithdrawnTreatmentAspergillosis1
2, 3CompletedTreatmentAspergillosis1
2, 3CompletedTreatmentAspergillosis, Allergic Bronchopulmonary1
3Active Not RecruitingSupportive CareHematopoietic/Lymphoid Cancer / Infections, Fungal1
3Active Not RecruitingTreatmentEye Infections, Fungal / Ulcerative keratitis1
3CompletedPreventionAntifungal Prophylaxis of Invasive Fungal Infections1
3CompletedSupportive CareInfection NOS / Pulmonary Complications1
3CompletedTreatmentAcquired Immune Deficiency Syndrome (AIDS) / Aspergillosis / Human Immunodeficiency Virus (HIV) Infections / Immunologic Deficiency Syndromes / Neutropenias1
3CompletedTreatmentAspergillosis2
3CompletedTreatmentAspergillosis / Candidiasis infection / Fungaemia / Mycoses1
3CompletedTreatmentAspergillosis / Invasive Fungal Infections1
3CompletedTreatmentCandidemia / Candidiasis, Invasive / Mycoses1
3CompletedTreatmentCandidiasis, Invasive1
3CompletedTreatmentEye Infections, Fungal / Ulcerative keratitis1
3CompletedTreatmentHaematological Malignancies / Invasive Fungal Infections1
3CompletedTreatmentInfection NOS / Leukemias / Malignant Lymphomas1
3CompletedTreatmentInfections, Fungal / Leukemias1
3CompletedTreatmentMycoses3
3CompletedTreatmentPossible Fungal Infection1
3RecruitingTreatmentDeep Mycosis1
3RecruitingTreatmentInfections, Fungal1
3TerminatedPreventionLeukemia, Myelocytic, Acute1
3TerminatedTreatmentInvasive Aspergillosis1
3TerminatedTreatmentCandidiasis infection1
3Unknown StatusPreventionPediatric Acute Leukemia Induction1
3WithdrawnTreatmentAspergillosis / Neuroaspergillosis / Pulmonary Invasive Aspergillosis1
4CompletedNot AvailableAspergillosis / Candidemia1
4CompletedNot AvailableHealthy Volunteers1
4CompletedNot AvailableInfections, Fungal1
4CompletedBasic ScienceInfections, Fungal1
4CompletedHealth Services ResearchHealthy Volunteers1
4CompletedPreventionProphylaxis Of Invasive Fungal Infections1
4CompletedTreatmentAspergillosis / Candidiasis infection / Cryptococcus Neoformans1
4CompletedTreatmentCandidemia / Candidiasis, Invasive1
4CompletedTreatmentFungus Infection1
4CompletedTreatmentInfections, Fungal1
4CompletedTreatmentInvader Fungal Infection1
4CompletedTreatmentInvasive Fungal Infections1
4CompletedTreatmentCandidiasis infection1
4Not Yet RecruitingDiagnosticDrug Drug Interaction (DDI) / Transplantation, Kidney1
4SuspendedTreatmentBlastomycosis1
4TerminatedPreventionInfection NOS1
4TerminatedTreatmentAspergillosis1
4Unknown StatusTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Invasive Aspergillosis1
4WithdrawnTreatmentAspergillosis/Blood / Aspergillosis/Invasive1
Not AvailableActive Not RecruitingNot AvailableInfections, Fungal / Voriconazole1
Not AvailableActive Not RecruitingNot AvailableSystemic Fungal Infections1
Not AvailableCompletedNot AvailableInvasive Fungal Infections1
Not AvailableCompletedNot AvailableNon-Melanoma Skin Carcinoma1
Not AvailableCompletedNot AvailableScedosporium Infection1
Not AvailableCompletedNot AvailableSerious Fungal Infections2
Not AvailableCompletedNot AvailableSystemic Fungal Infections1
Not AvailableCompletedNot AvailableSystemic Mycosis1
Not AvailableCompletedPreventionBlood Diseases / Graft Versus Host Disease (GVHD) / Hematopoietic Stem Cell Transplantation (HSCT) / Leukemias / Multiple Myeloma (MM) / Myelodysplastic Syndromes / Transplantation, Bone Marrow1
Not AvailableCompletedScreeningEfavirenz, Metabolism and Pharmacokinetics Changes1
Not AvailableCompletedSupportive CareMalignancies1
Not AvailableCompletedTreatmentCeftazidime / Ciprofloxacin / Pediatrics / Voriconazole1
Not AvailableCompletedTreatmentMycoses1
Not AvailableRecruitingNot AvailableInvasive Fungal Infections1
Not AvailableTerminatedNot AvailableInvasive Fungal Infections1
Not AvailableTerminatedOtherInvasive Aspergillosis1
Not AvailableUnknown StatusNot AvailablePulmonary Invasive Aspergillosis1
Not AvailableUnknown StatusTreatmentMycotic Corneal Ulcer1

Pharmacoeconomics

Manufacturers
  • Pfizer inc
  • Matrix laboratories ltd
Packagers
  • Cardinal Health
  • DSM Corp.
  • Pfizer Inc.
Dosage forms
FormRouteStrength
Injection, powder, for solutionIntravenous200 mg
Powder, for suspensionOral3 g
Powder, for suspensionOral40 mg/ml
TabletOral200 mg
TabletOral50 mg
Powder, for solutionIntravenous200 mg
Injection, powder, for solutionIntravenous10 mg/1mL
Injection, powder, lyophilized, for solutionIntravenous10 mg/1mL
Powder, for suspensionOral40 mg/1mL
SuspensionOral40 mg/1mL
TabletOral200 mg/1
TabletOral50 mg/1
Tablet, coatedOral200 mg/1
Tablet, coatedOral50 mg/1
Tablet, film coatedOral200 mg/1
Tablet, film coatedOral50 mg/1
Tablet, film coatedOral200 mg
Tablet, film coatedOral50 mg
Prices
Unit descriptionCostUnit
Vfend 40 mg/ml Suspension 75ml Bottle870.72USD bottle
Vfend iv 200 mg vial143.5USD vial
Vfend 200 mg tablet49.74USD tablet
Vfend 50 mg tablet12.43USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5116844No1992-05-262009-08-11Us
CA2295035No2005-04-192018-06-02Canada
CA2035314No2000-01-182011-01-30Canada
US5567817No1996-10-222016-05-24Us
US6632803No2003-10-142018-06-02Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)127-130 °CNot Available
water solubilityLowNot Available
logP1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0978 mg/mLALOGPS
logP1.65ALOGPS
logP1.82ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)12.71ChemAxon
pKa (Strongest Basic)2.27ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area76.72 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity95.28 m3·mol-1ChemAxon
Polarizability30.54 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9958
Blood Brain Barrier+0.9047
Caco-2 permeable+0.7219
P-glycoprotein substrateSubstrate0.591
P-glycoprotein inhibitor INon-inhibitor0.6113
P-glycoprotein inhibitor IINon-inhibitor0.8195
Renal organic cation transporterNon-inhibitor0.5354
CYP450 2C9 substrateNon-substrate0.727
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.5792
CYP450 1A2 substrateNon-inhibitor0.7491
CYP450 2C9 inhibitorInhibitor0.5203
CYP450 2D6 inhibitorNon-inhibitor0.8315
CYP450 2C19 inhibitorInhibitor0.5784
CYP450 3A4 inhibitorNon-inhibitor0.7011
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6649
Ames testNon AMES toxic0.7019
CarcinogenicityNon-carcinogens0.776
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.3469 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8791
hERG inhibition (predictor II)Non-inhibitor0.6282
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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0fh9-2593000000-630f0453fb0da8e2745d

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpropanes. These are organic compounds containing a phenylpropane moiety.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenylpropanes
Direct Parent
Phenylpropanes
Alternative Parents
Halopyrimidines / Fluorobenzenes / Aryl fluorides / Triazoles / Tertiary alcohols / Heteroaromatic compounds / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organofluorides
show 2 more
Substituents
Phenylpropane / Fluorobenzene / Halobenzene / Halopyrimidine / Aryl halide / Pyrimidine / Aryl fluoride / Heteroaromatic compound / 1,2,4-triazole / Tertiary alcohol
show 14 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
tertiary alcohol, triazole antifungal drug, conazole antifungal drug, pyrimidines, difluorobenzene (CHEBI:10023)

Targets

Kind
Protein
Organism
Yeast
Pharmacological action
Yes
Actions
Antagonist
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.
Gene Name
ERG11
Uniprot ID
P10613
Uniprot Name
Lanosterol 14-alpha demethylase
Molecular Weight
60674.965 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Morales IJ, Vohra PK, Puri V, Kottom TJ, Limper AH, Thomas CF Jr: Characterization of a lanosterol 14 alpha-demethylase from Pneumocystis carinii. Am J Respir Cell Mol Biol. 2003 Aug;29(2):232-8. Epub 2003 Feb 26. [PubMed:12606318]
  4. Sanguinetti M, Posteraro B, Fiori B, Ranno S, Torelli R, Fadda G: Mechanisms of azole resistance in clinical isolates of Candida glabrata collected during a hospital survey of antifungal resistance. Antimicrob Agents Chemother. 2005 Feb;49(2):668-79. [PubMed:15673750]
  5. Li X, Brown N, Chau AS, Lopez-Ribot JL, Ruesga MT, Quindos G, Mendrick CA, Hare RS, Loebenberg D, DiDomenico B, McNicholas PM: Changes in susceptibility to posaconazole in clinical isolates of Candida albicans. J Antimicrob Chemother. 2004 Jan;53(1):74-80. Epub 2003 Dec 4. [PubMed:14657086]
  6. Thompson GR 3rd, Lewis JS 2nd: Pharmacology and clinical use of voriconazole. Expert Opin Drug Metab Toxicol. 2010 Jan;6(1):83-94. doi: 10.1517/17425250903463878. [PubMed:19947892]
  7. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
  8. Xu Y, Sheng C, Wang W, Che X, Cao Y, Dong G, Wang S, Ji H, Miao Z, Yao J, Zhang W: Structure-based rational design, synthesis and antifungal activity of oxime-containing azole derivatives. Bioorg Med Chem Lett. 2010 May 1;20(9):2942-5. doi: 10.1016/j.bmcl.2010.03.014. Epub 2010 Mar 7. [PubMed:20362444]
  9. Xu J, Cao Y, Zhang J, Yu S, Zou Y, Chai X, Wu Q, Zhang D, Jiang Y, Sun Q: Design, synthesis and antifungal activities of novel 1,2,4-triazole derivatives. Eur J Med Chem. 2011 Jul;46(7):3142-8. doi: 10.1016/j.ejmech.2011.02.042. Epub 2011 Feb 24. [PubMed:21420761]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Nadp binding
Specific Function
This protein is involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. Form I catalyzes the N-oxygenation of secondary and tertiary amines.
Gene Name
FMO1
Uniprot ID
Q01740
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 1
Molecular Weight
60310.285 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Trimethylamine monooxygenase activity
Specific Function
Involved in the oxidative metabolism of a variety of xenobiotics such as drugs and pesticides. It N-oxygenates primary aliphatic alkylamines as well as secondary and tertiary amines. Plays an impor...
Gene Name
FMO3
Uniprot ID
P31513
Uniprot Name
Dimethylaniline monooxygenase [N-oxide-forming] 3
Molecular Weight
60032.975 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Details
5. Cytochrome P450 2C19
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55930.545 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Hyland R, Jones BC, Smith DA: Identification of the cytochrome P450 enzymes involved in the N-oxidation of voriconazole. Drug Metab Dispos. 2003 May;31(5):540-7. [PubMed:12695341]
  3. Murayama N, Imai N, Nakane T, Shimizu M, Yamazaki H: Roles of CYP3A4 and CYP2C19 in methyl hydroxylated and N-oxidized metabolite formation from voriconazole, a new anti-fungal agent, in human liver microsomes. Biochem Pharmacol. 2007 Jun 15;73(12):2020-6. doi: 10.1016/j.bcp.2007.03.012. Epub 2007 Mar 19. [PubMed:17433262]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  4. Drug Interactions & Labeling - FDA [Link]
Details
7. Cytochrome P450 2C9
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Niwa T, Shiraga T, Takagi A: Effect of antifungal drugs on cytochrome P450 (CYP) 2C9, CYP2C19, and CYP3A4 activities in human liver microsomes. Biol Pharm Bull. 2005 Sep;28(9):1805-8. [PubMed:16141567]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
  3. Voriconazole FDA label [File]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Prostaglandin-endoperoxide synthase activity
Specific Function
Converts arachidonate to prostaglandin H2 (PGH2), a committed step in prostanoid synthesis. Involved in the constitutive production of prostanoids in particular in the stomach and platelets. In gas...
Gene Name
PTGS1
Uniprot ID
P23219
Uniprot Name
Prostaglandin G/H synthase 1
Molecular Weight
68685.82 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Flockhart Table - Indiana University [Link]

Drug created on June 13, 2005 07:24 / Updated on November 18, 2018 13:31