TIOCONAZOLE

Details

Stereochemistry	RACEMIC
Molecular Formula	C16H13Cl3N2OS
Molecular Weight	387.711
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

ClC1=C(COC(CN2C=CN=C2)C3=CC=C(Cl)C=C3Cl)C=CS1

InChI

InChIKey=QXHHHPZILQDDPS-UHFFFAOYSA-N

InChI=1S/C16H13Cl3N2OS/c17-12-1-2-13(14(18)7-12)15(8-21-5-4-20-10-21)22-9-11-3-6-23-16(11)19/h1-7,10,15H,8-9H2

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020676Orig1s009lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.drugbank.ca/drugs/DB01007 | http://reference.medscape.com/drug/vagistat-1-tioconazole-topical-343494 | https://www.drugs.com/cdi/tioconazole.html

Tioconazole is an antifungal medication of the imidazole class used to treat infections caused by a fungus or yeast. Tioconazole is a broad-spectrum imidazole antifungal agent that inhibits the growth of human pathogenic yeasts. Tioconazole exhibits fungicidal activity in vitro against Candida albicans, other species of the genus Candida, and against Torulopsis glabrata. Tioconazole prevents the growth and function of some fungal organisms by interfering with the production of substances needed to preserve the cell membrane. This drug is effective only for infections caused by fungal organisms. Tioconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme that converts lanosterol to ergosterol, an essential component of the yeast membrane. In this way, tioconazole inhibits ergosterol synthesis, resulting in increased cellular permeability. Tioconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms and the uptake of purine, impair triglyceride and/or phospholipid biosynthesis, and inhibit the movement of calcium and potassium ions across the cell membrane by blocking the ion transport pathway known as the Gardos channel. Side effects (for the women's formulas) may include temporary burning/irritation of the vaginal area, moderate drowsiness, headache similar to a sinus headache, hives, and upper respiratory infection.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cytochrome P450 51 28 Target ID: CHEMBL1780 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10445042	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Vaginal candidiasis 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020676Orig1s009lbl.pdf	Curative		Approved 8429	TZ-3 Approved Use Directions before using this product read the enclosed brochure and instructions on foil packet for complete directions and information adults and children 12 years and over: 1.Open the foil packet just before use and remove purple cap. 2.Insert entire contents of applicator into the vagina at bedtime. Throw applicator away after use. children under 12 years of age: ask a doctor, Do not use if sealed foil packet torn, open, or incompletely sealed. 1-DOSE TREATMENT TIOCONAZOLE OINTMENT 6.5% VAGINAL ANTIFUNGAL DIRECTIONS FOR USE Tear open foil packet just before using. It is best to use at bedtime. Remove applicator and plunger from packet. Applicator is prefilled with vaginal ointment. While firmly holding the purple-capped end of the applicator, push the tip of the plunger into the base of applicator. REMOVE PURPLE CAP from top of applicator with a pull-twist action. Insert the applicator Lie on your back with your knees bent. Gently insert applicator into the vagina as far as it will go comfortably. Push the plunger into the applicator until it will go no farther. Withdraw the applicator and plunger and dispose of it in the wastebasket. Do not flush. DO NOT USE TAMPONS while using this medicine. Use sanitary napkins instead. PLEASE READ EDUCATIONAL BROCHURE FOR ADDITIONAL INFORMATION. 4260000 P6 DISTRIBUTED BY PERRIGO ALLEGAN, MI 48010 U.S.A. Tioconazole_oint_fig1-01 Tioconazole_oint_fig2-01 Tioconazole_oint_fig3-01 Launch Date 1983

C_max

Value	Dose	Co-administered	Analyte	Population
13 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6873743/	6 % single, vaginal dose: 6 % route of administration: Vaginal experiment type: SINGLE co-administered:		TIOCONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
150 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/6873743/	6 % single, vaginal dose: 6 % route of administration: Vaginal experiment type: SINGLE co-administered:		TIOCONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
6.5 % 1 times / day multiple, topical Highest studied dose Dose: 6.5 %, 1 times / day Route: topical Route: multiple Dose: 6.5 %, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/3524439/	unhealthy, adult n = 80 Health Status: unhealthy Condition: vulvovaginal candidiasis Age Group: adult Sex: unknown Population Size: 80 Sources: https://pubmed.ncbi.nlm.nih.gov/3524439/	Sources: https://pubmed.ncbi.nlm.nih.gov/3524439/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP 111 CYP1A2 1524 CYP2C19 1478 CYP2E1 882	UGT1A4 347 UGT1A3 422

Drug as perpetrator

Target	Modality	Activity
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11854151/	yes [Ki 0.02 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11854151/	yes [Ki 0.4 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11854151/	yes [Ki 0.4 uM]
CYP2E1 970	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/11854151/	yes [Ki 0.4 uM]
CYP 147	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/2886308/	yes

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
UGT1A3 422	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20304965/	yes
UGT1A4 347	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/20304965/	yes

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY565897	https://www.001chemical.com/chem/65899-73-2
3B Scientific (Wuhan) Corp	3B2-0224	http://www.3bsc.com/index/pro_info.php?id=19580
AA Blocks	AA00IBGM	http://www.aablocks.com/goods/Goods/detail?id=AA00IBGM
AHH Chemical co.,ltd	API-1210	http://www.ahhchemical.com/product/API-1210.html
AK Scientific, Inc. (AKSCI)	H949	http://www.aksci.com/item_detail.php?cat=H949
Aaron Chemicals	AR00IC8E	http://www.aaronchem.com/65899-73-2
AbMole Bioscience	M6014	http://www.abmole.com/products/tioconazole.html
Achemtek	0104-023439	http://www.achemtek.com/65899-73-2
Alfa Chemistry	AP65899732	https://reagents.alfa-chemistry.com/product/tioconazole-cas-65899-73-2-14745.html
Ark Pharm	AK546825	http://www.arkpharminc.com/products/65899-73-2.html
Aurora Fine Chemicals LLC	A17.904.336	http://online.aurorafinechemicals.com/info?ID=A17.904.336
Aurum Pharmatech LLC	KM0968	http://www.Aurumpharmatech.com/Product/ProductDetails/KM0968
BLD Pharm	BD34537	http://www.bldpharm.com/products/65899-73-2.html
BioCrick	BCC4867	http://www.biocrick.com/Tioconazole-BCC4867.html
CSNpharm	CSN16446	https://www.csnpharm.com/products/tioconazole.html
Chem Scene	CS-2360	http://www.chemscene.com/65899-73-2.html
ChemMol	30103053	http://www.chemmol.com/chemmol/30103053.html
ChemMol	49424003	http://www.chemmol.com/chemmol/49424003.html
Chemspace	CSSB00000044051	https://chem-space.com/CSSB00000044051
Clearsynth	CS-T-44433	https://www.clearsynth.com/en/CST44433.html
DC Chemicals	DC31885	http://www.dcchemicals.com//product_show-Tioconazole.html
Finetech	FT-0630756	http://www.finetechnology-ind.com/prod/detail/pub/65899-73-2.html
Glentham Life Sciences	GA0099	http://www.glentham.com/products/product/GA0099/
Hairui	HR122364	http://www.hairuichem.com/en/product/65899-73-2.html
LGC Standards	LGCFOR1307.00	https://www.lgcstandards.com/US/en/p/LGCFOR1307.00
LGC Standards	MM1307.00	https://www.lgcstandards.com/US/en/p/MM1307.00
Lab Network	LN00195638	https://labnetwork.com/frontend-app/p/#!/moleculedetails/LN00195638
MedChem Express	HY-B0319	https://www.medchemexpress.com/Tioconazole.html
Molcore	MC565897	https://www.molcore.com/product/65899-73-2
OChem	5408	http://www.ocheminc.com/index.php?act=psearch&pid=899T732
Sigma-Aldrich	32099_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/32099?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	Y0000282_SIAL	https://www.sigmaaldrich.com/catalog/product/sial/y0000282?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	03907_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/03907?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	1667439_USP	https://www.sigmaaldrich.com/catalog/product/usp/1667439?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Smolecule	S545399	http://www.smolecule.com/products/s545399
Smolecule	S772615	https://www.smolecule.com/products/s772615
THE BioTek	bt-285370	https://www.thebiotek.com/product/inhibitors/bt-285370
Yuhao Chemical	RT10351	http://www.chemyuhao.com/65899-73-2.html
abcr GmbH	AB349653	http://www.abcr.com/shop/en/AB349653
abcr GmbH	AB402860	http://www.abcr.com/shop/en/AB402860
eNovation Chemicals	D673739	https://www.enovationchem.com/ProductDetails.asp?ProductID=D673739
iChemical	EBD39607	http://www.ichemical.com/chemicals/cas-65899-73-2

PubMed

Title	Date	PubMed
Antifungal activity of tioconazole (UK-20,349), a new imidazole derivative.	1979 Apr	464592
Current and emerging azole antifungal agents.	1999 Jan	9880474
Synthesis and antifungal activity of novel pyrano[2',3':4,5]thiazolo[2,3-b]quinazolines, pyrido[2',3':4,5]thiazolo[2,3-b]quinazolines and pyrazolo[2',3':4,5]thiazolo[2,3-b]quinazolines.	2000 Apr	10966160
Ciclopiroxolamine: in vitro antifungal activity against clinical yeast isolates.	2002 Nov	12431873
In vivo patterns of resistance to the HIV attachment inhibitor BMS-488043.	2011 Feb	21078948

Patents

Sample Use Guides

In Vivo Use Guide

Insert 1 applicatorful (5 g of 6.5% ointment) intravaginally qHS once

Route of Administration: Vaginal

In Vitro Use Guide

The compounds were dissolved in dimethyl formamnide, and water was added to give a final Tioconazole concentration of 1 mg/ml in 10% dimethyl formamide-water. From this solution, serial twofold dilutions of the compounds in water were incorporated into diagnostic sensitivity test agar over an appropriate concentration range (normally 100 mkg/ml down to 0.0 1mkg/ml). Organisms were inoculated onto the surface of the agar, using a multipoint inoculator (Denley Instruments) which delivers approximately 1 id of the fungal inoculum. Candida spp., Torulopsis glabtata, and Cryptococcus neofomnans were grown overnight at 37 C in brain heart infusion broth (Difco Laboratories). The concentration of cells in the culture was determined in a hemocytometer and then appropriately diluted in broth to10 cells per ml. MICs were read after incubation at 37 C for 48 h.

Name

Type

Language

TIOCONAZOLE

Official Name

English

TIOCONAZOLE [ORANGE BOOK]

Common Name

English

VAGISTAT-1

Brand Name

English

TIOCONAZOLE [VANDF]

Common Name

English

TIOCONAZOLE [JAN]

Common Name

English

NSC-759169

Code

English

tioconazole [INN]

Common Name

English

Tioconazole [WHO-DD]

Common Name

English

TIOCONAZOLE [USAN]

Common Name

English

UK-20,349

Code

English

TIOCONAZOLE [MI]

Common Name

English

TIOCONAZOLE [MART.]

Common Name

English

TIOCONAZOLE [EP MONOGRAPH]

Common Name

English

VAGISTAT

Brand Name

English

UK-20349

Code

English

TIOCONAZOLE [USP-RS]

Common Name

English

TIOCONAZOLE [USP IMPURITY]

Common Name

English

TIOCONAZOLE [INCI]

Common Name

English

TIOCONAZOLE [USP MONOGRAPH]

Common Name

English

1H-IMIDAZOLE, 1-(2-((2-CHLORO-3-THIENYL)METHOXY)-2-(2,4-DICHLOROPHENYL)ETHYL)-

Systematic Name

English

Classification Tree Code System Code

NDF-RT

N0000008217