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Details

Stereochemistry ABSOLUTE
Molecular Formula C22H17F2N5OS
Molecular Weight 437.465
Optical Activity UNSPECIFIED
Defined Stereocenters 2 / 2
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of ISAVUCONAZOLE

SMILES

C[C@@H](C1=NC(=CS1)C2=CC=C(C=C2)C#N)[C@](O)(CN3C=NC=N3)C4=CC(F)=CC=C4F

InChI

InChIKey=DDFOUSQFMYRUQK-RCDICMHDSA-N
InChI=1S/C22H17F2N5OS/c1-14(21-28-20(10-31-21)16-4-2-15(9-25)3-5-16)22(30,11-29-13-26-12-27-29)18-8-17(23)6-7-19(18)24/h2-8,10,12-14,30H,11H2,1H3/t14-,22+/m0/s1

HIDE SMILES / InChI

Molecular Formula C22H17F2N5OS
Molecular Weight 437.465
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry
Defined Stereocenters 2 / 2
E/Z Centers 0
Optical Activity UNSPECIFIED

Description

Isavuconazole is an active form of isavuconazonium, a prodrug which is marketed under the name Cresemba. Isavuconazole inhibits lanosterol 14-alpha demethylase (or CYP51A1) and leads to the accumulation of ergosterol toxic precursors in the fungal cytoplasm. Isavuconazole is indicated for the treatment of invasive aspergillosis and invasive mucormycosis.

CNS Activity

Originator

Approval Year

PubMed

PubMed

TitleDatePubMed
Drug evaluation: BAL-8557--a novel broad-spectrum triazole antifungal.
2006 Aug
Multiple-dose pharmacokinetics and safety of the new antifungal triazole BAL4815 after intravenous infusion and oral administration of its prodrug, BAL8557, in healthy volunteers.
2006 Jan
Single-ascending-dose pharmacokinetics and safety of the novel broad-spectrum antifungal triazole BAL4815 after intravenous infusions (50, 100, and 200 milligrams) and oral administrations (100, 200, and 400 milligrams) of its prodrug, BAL8557, in healthy volunteers.
2006 Jan
In vitro activity of a new triazole BAL4815, the active component of BAL8557 (the water-soluble prodrug), against Aspergillus spp.
2006 Jan
Investigational antimicrobial drugs for bloodstream infections.
2008 Aug
New and investigational triazole agents for the treatment of invasive fungal infections.
2008 Dec
Isavuconazole: a new and promising antifungal triazole for the treatment of invasive fungal infections.
2008 Dec
New and emerging treatments for fungal infections.
2008 Jan
Cryptococcus gattii: An Emerging Cause of Fungal Disease in North America.
2009
In vitro activities of isavuconazole against opportunistic filamentous and dimorphic fungi.
2009 Feb
Efficacy of isavuconazole, voriconazole and fluconazole in temporarily neutropenic murine models of disseminated Candida tropicalis and Candida krusei.
2009 Jan
Antifungal susceptibilities among different serotypes of Cryptococcus gattii and Cryptococcus neoformans.
2009 Jan
In vitro activity of isavuconazole against Trichosporon, Rhodotorula, Geotrichum, Saccharomyces and Pichia species.
2009 Jul
In vitro antifungal activity of isavuconazole against 345 mucorales isolates collected at study centers in eight countries.
2009 Jun
New triazoles and echinocandins: mode of action, in vitro activity and mechanisms of resistance.
2009 Oct
Comparison of adverse events between oral and intravenous formulations of antimicrobial agents: a systematic review of the evidence from randomized trials.
2009 Oct
New generation azole antifungals in clinical investigation.
2009 Sep
Clinical safety and tolerability issues in use of triazole derivatives in management of fungal infections.
2010
In vitro activities of eight antifungal drugs against 55 clinical isolates of Fonsecaea spp.
2010 Apr
[Recent advances in the study of new antifungal lead compounds].
2010 Aug
Rhinocladiella aquaspersa, proven agent of verrucous skin infection and a novel type of chromoblastomycosis.
2010 Aug
In vitro antifungal susceptibilities and amplified fragment length polymorphism genotyping of a worldwide collection of 350 clinical, veterinary, and environmental Cryptococcus gattii isolates.
2010 Dec
Novel triazole antifungal drugs: focus on isavuconazole, ravuconazole and albaconazole.
2010 Feb
Isavuconazole: a comprehensive review of spectrum of activity of a new triazole.
2010 Nov
Antifungal susceptibility, serotyping, and genotyping of clinical Cryptococcus neoformans isolates collected during 18 years in a single institution in Madrid, Spain.
2010 Nov
In vitro activity of isavuconazole against 140 reference fungal strains and 165 clinically isolated yeasts from Japan.
2010 Oct
Microsatellite typing and susceptibilities of serial Cryptococcus neoformans isolates from Cuban patients with recurrent cryptococcal meningitis.
2010 Oct 4
Opportunistic fungi: a view to the future.
2010 Sep
In vitro antifungal activities of isavuconazole and comparators against rare yeast pathogens.
2010 Sep
Chromatographic and electrophoretic techniques used in the analysis of triazole antifungal agents-a review.
2010 Sep 15
In vitro activity of isavuconazole against 208 Aspergillus flavus isolates in comparison with 7 other antifungal agents: assessment according to the methodology of the European Committee on Antimicrobial Susceptibility Testing.
2011 Dec
Isavuconazole activity against Aspergillus lentulus, Neosartorya udagawae, and Cryptococcus gattii, emerging fungal pathogens with reduced azole susceptibility.
2013 Sep
Isavuconazole: Pharmacology, Pharmacodynamics, and Current Clinical Experience with a New Triazole Antifungal Agent.
2015 Nov
Isavuconazole: A New Broad-Spectrum Triazole Antifungal Agent.
2015 Nov 15
Patents

Sample Use Guides

In Vivo Use Guide
Loading Dose: 372 mg isavuconazonium sulfate (equivalent to 200 mg of isavuconazole) every 8 hours for 6 doses (48 hours) via oral (2 capsules) or intravenous administration (1 reconstituted vial) Maintenance Dose: 372 mg isavuconazonium sulfate (equivalent to 200 mg of isavuconazole) once daily via oral (2 capsules) or intravenous administration (1 reconstituted vial) starting 12 to 24 hours after the last loading dose.
Route of Administration: Oral; Intravenous
In Vitro Use Guide
Isavuconazole exhibited MIC50 values of 1–4 ug/ mL and MIC90 values of 4–16 ug/mL, against Mucorales isolates. MIC90 against Aspergillus fumigatus was 0.5–2 ug/ml, MIC90 against Aspergillus terreus was 0.5–4 ug/ml, MIC90 against Aspergillus flavus was 1–16 ug/ml, MIC90 against Aspergillus niger was 2–4 ug/ml.
Substance Class Chemical
Created
by admin
on Mon Oct 21 19:48:41 UTC 2019
Edited
by admin
on Mon Oct 21 19:48:41 UTC 2019
Record UNII
60UTO373KE
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ISAVUCONAZOLE
INN   MI   WHO-DD  
INN  
Official Name English
ISAVUCONAZOLE [WHO-DD]
Common Name English
4-(2-((2R,3R)-3-(2,5-DIFLUOROPHENYL)-3-HYDROXY-4-(1H-1,2,4-TRIAZOL-1-YL)BUTAN-2-YL)-1,3-THIAZOL-4-YL)BENZONITRILE
Systematic Name English
BAL-4815
Code English
ISAVUCONAZOLE [MI]
Common Name English
ISAVUCONAZOLE [INN]
Common Name English
Classification Tree Code System Code
WHO-ATC J02AC05
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
NCI_THESAURUS C514
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
NDF-RT N0000175487
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
Code System Code Type Description
WIKIPEDIA
ISAVUCONAZOLE
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY
EPA CompTox
241479-67-4
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY
NCI_THESAURUS
C64543
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY
ChEMBL
CHEMBL409153
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY
NDF-RT
N0000187061
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY Organic Cation Transporter 2 Inhibitors [MoA]
CAS
241479-67-4
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY
INN
8783
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY
EVMPD
SUB128138
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY
NDF-RT
N0000185503
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY P-Glycoprotein Inhibitors [MoA]
RXCUI
1720882
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY RxNorm
MERCK INDEX
M6419
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY Merck Index
NDF-RT
N0000182141
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY Cytochrome P450 3A4 Inhibitors [MoA]
PUBCHEM
6918485
Created by admin on Mon Oct 21 19:48:41 UTC 2019 , Edited by admin on Mon Oct 21 19:48:41 UTC 2019
PRIMARY
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METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
FECAL
METABOLIC ENZYME -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
METABOLIC ENZYME -> INDUCER
METABOLIC ENZYME -> INHIBITOR
METABOLIC ENZYME -> INHIBITOR
TARGET ORGANISM->INHIBITOR
METABOLIC ENZYME -> INHIBITOR
METABOLIC ENZYME -> INDUCER
METABOLIC ENZYME -> INDUCER
BINDER->LIGAND
BINDING
EXCRETED UNCHANGED
URINE
METABOLIC ENZYME -> SUBSTRATE
TARGET ORGANISM->INHIBITOR
TARGET ORGANISM->INHIBITOR
METABOLIC ENZYME -> INDUCER
METABOLIC ENZYME -> INDUCER
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC INTRAVENOUS ADMINISTRATION

ORAL BIOAVAILABILITY PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC INTRAVENOUS ADMINISTRATION