ALBACONAZOLE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H16ClF2N5O2
Molecular Weight	431.823
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

C[C@@H](N1C=NC2=C(C=CC(Cl)=C2)C1=O)[C@](O)(CN3C=NC=N3)C4=C(F)C=C(F)C=C4

InChI

InChIKey=UHIXWHUVLCAJQL-MPBGBICISA-N

InChI=1S/C20H16ClF2N5O2/c1-12(28-11-25-18-6-13(21)2-4-15(18)19(28)29)20(30,8-27-10-24-9-26-27)16-5-3-14(22)7-17(16)23/h2-7,9-12,30H,8H2,1H3/t12-,20-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20112166
Curator's Comment: description was created based on several sources, including: https://newdrugapprovals.org/2014/09/09/10613/ | http://adisinsight.springer.com/drugs/800009452

Albaconazole is a triazole antifungal. Azoles are important antifungal compounds, and all drugs in this class inhibit ergosterol synthesis by blocking the 14-α-demethylase enzyme, resulting in the accumulation of toxic methylsterols that may culminate in fungal death. Albaconazole, an oral agent that has demonstrated high levels of bioavailability and potent antifungal activity. It was under development for the treatment of onychomycosis, vulvovaginal candidiasis. Also, albaconazole was evaluated in phase I, a randomized, placebo-controlled clinical trial in patients with tinea pedis. No serious adverse effects occurred in the studies involving albaconazole. However, this researches on this drug were discontinued.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sterol C14alpha demethylase 1 Target ID: Sterol C14alpha demethylase Sources: https://www.ncbi.nlm.nih.gov/pubmed/10952601 \| http://en.pharmacodia.com/web/drug/1_799.html	Inhibitor 8504

Conditions

Condition	Modality	Highest Phase	Product
Onychomycosis 18 Sources: https://www.ncbi.nlm.nih.gov/pubmed/23706639	Curative	Phase II 1147	Unknown Approved Use Unknown
Candidiasis vulvovaginitis 1 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18095765	Curative	Phase II 1147	Unknown Approved Use Unknown
Tinea pedis 28 Sources: http://adisinsight.springer.com/drugs/800009452	Curative	Phase I 438	Unknown Approved Use Unknown

C_max

Value	Dose	Analyte	Population
235 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390369	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	6-HYDROXYALBACONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
1670 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390369	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ALBACONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
226 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390369	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	6-HYDROXYALBACONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
2350 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390369	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ALBACONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

AUC

Value	Dose	Analyte	Population
53474.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390369	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	6-HYDROXYALBACONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
107796.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390369	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ALBACONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
51216.1 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390369	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	6-HYDROXYALBACONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
114472.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390369	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ALBACONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

T_1/2

Value	Dose	Analyte	Population
72.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390369	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	6-HYDROXYALBACONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
64.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390369	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ALBACONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
67.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390369	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	6-HYDROXYALBACONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN
57.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/23390369	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	ALBACONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
400 mg 1 times / week multiple, oral Highest studied dose Dose: 400 mg, 1 times / week Route: oral Route: multiple Dose: 400 mg, 1 times / week Sources: https://pubmed.ncbi.nlm.nih.gov/23706639	unhealthy Health Status: unhealthy Sex: M+F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/23706639	Other AEs: Aspartate aminotransferase increased, Aspartate aminotransferase increased... Other AEs: Aspartate aminotransferase increased Aspartate aminotransferase increased Dizziness (1%) Diarrhea (3%) Blood creatine phosphokinase increase (4%) Nause (3%) Alanine aminotransferase increase (3%) Upper respiratory tract infection (3%) vomiting (1%) Constipation (1%) Aspartate aminotransferase increased (2%) Abdominal discomfor (1%) Blood glucose increased (2%) Neutrophil count decrease (1%) Gastroenteritis (1%) Sources: https://pubmed.ncbi.nlm.nih.gov/23706639

AEs

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P002H1X	https://www.1pchem.com/search?query=1P002H1X
AK Scientific	3132AL	https://aksci.com/item_detail.php?cat=3132AL
Angene	AGN-PC-0WH1VT	http://www.angenechemical.com/productshow/AGN-PC-0WH1VT.html
AstaTech	42137	http://astatechinc.com/CPSResult.php?CRNO=42137
BOC Sciences	187949-02-6	http://www.bocsci.com/description.asp?cas=187949-02-6
Combi-Blocks	QJ-5552	http://www.combi-blocks.com/cgi-bin/find.cgi?QJ-5552
eMolecules	29933742	https://orderbb.emolecules.com/search/#?query=29933742
eMolecules	48666139	https://orderbb.emolecules.com/search/#?query=48666139
mcule	MCULE-1402799089	https://mcule.com/MCULE-1402799089/
mcule	MCULE-8427440185	https://mcule.com/MCULE-8427440185/
MuseChem	R010989	https://www.musechem.com/product/R010989.html
Toronto Research Chemicals	A511450	https://www.trc-canada.com/product-detail/?CatNum=A511450
Toronto Research Chemicals	H954500	https://www.trc-canada.com/product-detail/?CatNum=H954500
Wonderchem	WD05HEH	http://www.wonder-chem.com/search.html?text=WD05HEH

PubMed

Title	Date	PubMed
Design, synthesis, and structure-activity relationship studies of novel fused heterocycles-linked triazoles with good activity and water solubility.	2014-05-08	24564525
Chromatographic and electrophoretic techniques used in the analysis of triazole antifungal agents-a review.	2010-09-15	20801303
[Recent advances in the study of new antifungal lead compounds].	2010-08	21351583
Novel triazole antifungal drugs: focus on isavuconazole, ravuconazole and albaconazole.	2010-02	20112166
Clinical safety and tolerability issues in use of triazole derivatives in management of fungal infections.	2010	21701616
New triazoles and echinocandins: mode of action, in vitro activity and mechanisms of resistance.	2009-10	19803707
New generation azole antifungals in clinical investigation.	2009-09	19678798
Triazole derivatives with antifungal activity: a pharmacophore model study.	2009-01-29	19172871
Influence of Ecto-nucleoside triphosphate diphosphohydrolase activity on Trypanosoma cruzi infectivity and virulence.	2009	19255624
New and investigational triazole agents for the treatment of invasive fungal infections.	2008-12	19129062
New and emerging treatments for fungal infections.	2008-01	18063600
[Identification and susceptibility against fluconazole and albaconazole of 100 yeasts' strains isolated from vaginal discharge].	2007-12-31	18095765
Antifungal susceptibilities of the species of the Pseudallescheria boydii complex.	2006-12	17015631
Voriconazole in the management of nosocomial invasive fungal infections.	2006-06	18360588
Newer triazole antifungal agents: pharmacology, spectrum, clinical efficacy and limitations.	2006-06	16732713
In vitro activities of new and conventional antimycotics against fluconazole-susceptible and non-susceptible Brazilian Candida spp. isolates.	2006-05	16681814
Cryptococcus gattii: in vitro susceptibility to the new antifungal albaconazole versus fluconazole and voriconazole.	2005-09	16320494
Emerging azole antifungals.	2005-02	15757401
Measurement of the sign and the magnitude of heteronuclear coupling constants from spin-state-edited J-cross-polarization NMR experiments.	2004-10	15366058
In vitro and in vivo efficacies of the new triazole albaconazole against Cryptococcus neoformans.	2004-02	14742184
In vitro interactions of licensed and novel antifungal drugs against Fusarium spp.	2004-01	14761725
Specific treatment of Chagas disease: current status and new developments.	2001-12	11964893
In vitro antifungal activities of the new triazole UR-9825 against clinically important filamentous fungi.	2001-09	11502542
In vitro activities of four novel triazoles against Scedosporium spp.	2001-07	11408242
In-vitro comparative activity of UR-9825, itraconazole and fluconazole against clinical isolates of Candida spp.	1999-08	10473237
New azole antifungals. 3. Synthesis and antifungal activity of 3-substituted-4(3H)-quinazolinones.	1998-05-21	9599237

Patents

Sample Use Guides

In Vivo Use Guide

100, 200 and 400 mg weekly for 24 or 36 weeks.

Route of Administration: Oral

In Vitro Use Guide

The clinically relevant intracellular amastigote forms, proliferating in cultured Vero cells at 37°C, were more susceptible to Albaconazole than epimastigotes: the MIC required to reduce infected cells by 99% and the IC50 (concentration of the drug required to reduce infected cells by 50%) were in this case 10 nM and 1 nM, respectively.

Name

Type

Language

ALBACONAZOLE

Official Name

English

W-0027

Preferred Name

English

4(3H)-QUINAZOLINONE, 7-CHLORO-3-((1R,2R)-2-(2,4-DIFLUOROPHENYL)-2-HYDROXY-1-METHYL-3-(1H-1,2,4-TRIAZOL-1-YL)PROPYL)-

Systematic Name

English

UR-9825

Code

English

albaconazole [INN]

Common Name

English

7-Chloro-3-[(1R,2R)-2-(2,4-difluorophenyl)-2-hydroxy-1-methyl-3-(1H-1,2,4-triazol-1-yl)propyl]quinazolin-4(3H)-one

Systematic Name

English

W0027

Code

English

ALBACONAZOLE [USAN]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C514