TERCONAZOLE

Details

Stereochemistry	RACEMIC
Molecular Formula	C26H31Cl2N5O3
Molecular Weight	532.462
Optical Activity	( + / - )
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC(C)N1CCN(CC1)C2=CC=C(OC[C@@H]3CO[C@](CN4C=NC=N4)(O3)C5=C(Cl)C=C(Cl)C=C5)C=C2

InChI

InChIKey=BLSQLHNBWJLIBQ-ZEQKJWHPSA-N

InChI=1S/C26H31Cl2N5O3/c1-19(2)31-9-11-32(12-10-31)21-4-6-22(7-5-21)34-14-23-15-35-26(36-23,16-33-18-29-17-30-33)24-8-3-20(27)13-25(24)28/h3-8,13,17-19,23H,9-12,14-16H2,1-2H3/t23-,26-/m1/s1

HIDE SMILES / InChI

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019579s037,019641s030,019964s032lbl.pdf
Curator's Comment: description was created based on several sources, including http://reference.medscape.com/drug/terazol-3-terconazole-vaginal-342596 | https://www.drugs.com/cdi/terconazole-cream.html | https://www.drugbank.ca/drugs/DB00251 | https://www.ncbi.nlm.nih.gov/pubmed/3891537

Terconazole is an antifungal drug used to treat vaginal yeast infection. Terconazole may exert its antifungal activity by disrupting normal fungal cell membrane permeability. Terconazole and other triazole antifungal agents inhibit cytochrome P450 "14-alpha-demethylase" in susceptible fungi, which leads to the accumulation of lanosterol and other methylated sterols and a decrease in ergosterol concentration. Depletion of ergosterol in the membrane disrupts the structure and function of the fungal cell leading to a decrease or inhibition of fungal growth. During controlled clinical studies conducted in the United States, 521 patients with vulvovaginal candidiasis were treated with terconazole 0.4% vaginal cream. Based on comparative analyses with placebo, the adverse experiences considered most likely related to terconazole 0.4% vaginal cream were a headache and body pain. Fever and chills, vulvovaginal burning, itching, and irritation have also been reported. The adverse drug experience on terconazole most frequently causing discontinuation was vulvovaginal itching.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Pregnane X receptor 35 Target ID: CHEMBL3401 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20966043	Partial Agonist 290		8.9 µM [EC50]
Cytochrome P450 51 28 Target ID: CHEMBL1780 Sources: https://www.ncbi.nlm.nih.gov/pubmed/17194716	Inhibitor 8297		3.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Vulvovaginal candidiasis 9 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/019579s037,019641s030,019964s032lbl.pdf	Curative		Approved 8429	TERAZOL 7 Approved Use Terconazole vaginal cream 0.4% is indicated for the local treatment of vulvovaginal candidiasis (moniliasis). As terconazole vaginal cream 0.4% is effective only for vulvovaginitis caused by the genus Candida, the diagnosis should be confirmed by KOH smears and/or cultures. Launch Date 1987
HIV infection 21 Sources: https://clinicaltrials.gov/ct2/show/NCT01813162	Preventing		Phase I 428	TERAZOL 7 Approved Use Terconazole vaginal cream 0.4% is indicated for the local treatment of vulvovaginal candidiasis (moniliasis). As terconazole vaginal cream 0.4% is effective only for vulvovaginitis caused by the genus Candida, the diagnosis should be confirmed by KOH smears and/or cultures. Launch Date 1987

C_max

Value	Dose	Co-administered	Analyte	Population
5.9 ng/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/019579s035,019641s028,019964s030lbl.pdf	40 mg 1 times / day multiple, vaginal dose: 40 mg route of administration: Vaginal experiment type: MULTIPLE co-administered:		TERCONAZOLE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6.9 h OTHER GOV http://rxproduct.taro.ca/media/oMedia/Taro-Terconazole%20Vag%20Cr%20PM.pdf	30 mg single, oral dose: 30 mg route of administration: Oral experiment type: SINGLE co-administered:		TERCONAZOLE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
5.1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/19579slr026,19641slr022,19964slr021_terazol_lbl.pdf			TERCONAZOLE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
0.8 % 1 times / day multiple, vaginal Recommended Dose: 0.8 %, 1 times / day Route: vaginal Route: multiple Dose: 0.8 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021735s000_Terconazole_Vaginal_MedR.pdf	unhealthy, adult n = 243 Health Status: unhealthy Condition: vulvovaginal candidiasis Age Group: adult Sex: F Population Size: 243 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021735s000_Terconazole_Vaginal_MedR.pdf	Disc. AE: Allergic reaction, Vaginitis... AEs leading to discontinuation/dose reduction: Allergic reaction Vaginitis Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021735s000_Terconazole_Vaginal_MedR.pdf

AEs

AE	Significance	Dose	Population
Allergic reaction	Disc. AE	0.8 % 1 times / day multiple, vaginal Recommended Dose: 0.8 %, 1 times / day Route: vaginal Route: multiple Dose: 0.8 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021735s000_Terconazole_Vaginal_MedR.pdf	unhealthy, adult n = 243 Health Status: unhealthy Condition: vulvovaginal candidiasis Age Group: adult Sex: F Population Size: 243 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021735s000_Terconazole_Vaginal_MedR.pdf
Vaginitis	Disc. AE	0.8 % 1 times / day multiple, vaginal Recommended Dose: 0.8 %, 1 times / day Route: vaginal Route: multiple Dose: 0.8 %, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021735s000_Terconazole_Vaginal_MedR.pdf	unhealthy, adult n = 243 Health Status: unhealthy Condition: vulvovaginal candidiasis Age Group: adult Sex: F Population Size: 243 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/021735s000_Terconazole_Vaginal_MedR.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP51A1 1

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP51A1 1	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021735s004lbl.pdf Page: 5.0	yes

Sourcing

Vendor/Aggregator	ID	URL
Hairui	HR101145
Molnova	M15592
MuseChem	R060488
NCI Plated 2007	331942
Selleck Chemicals	S5033
TargetMol	T2213
ZINC	ZINC000000897382	http://zinc15.docking.org/substances/ZINC000000897382
eMolecules	42766645
mcule	MCULE-6445664010

PubMed

Title	Date	PubMed
Paecilomyces lilacinus vaginitis in an immuno-competent patient.	2003 Sep	14519255
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Inhibition of the enzymatic activity of heme oxygenases by azole-based antifungal drugs.	2006 Oct	16807364
Enantioselective separation of azole compounds by EKC. Reversal of migration order of enantiomers with CD concentration.	2007 Aug	17607804
Identification of antifungal compounds active against Candida albicans using an improved high-throughput Caenorhabditis elegans assay.	2009 Sep 14	19750012
Chromatographic and electrophoretic techniques used in the analysis of triazole antifungal agents-a review.	2010 Sep 15	20801303
Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2.	2011 Jul 14	21599003

Patents

Sample Use Guides

In Vivo Use Guide

One full applicator (5 g) of TERAZOL® 7 Vaginal Cream (20 mg terconazole) should be administered intravaginally once daily at bedtime for seven consecutive days. One full applicator (5 g) of TERAZOL® 3 Vaginal Cream (40 mg terconazole) should be administered intravaginally once daily at bedtime for three consecutive days. One TERAZOL® 3 Vaginal Suppository (80 mg terconazole) should be administered intravaginally once daily at bedtime for three consecutive days.

Route of Administration: Vaginal

In Vitro Use Guide

Terconazole was dissolved in methyl alcohol to a final concentration of 250 mkg/ml. 20 mkl of these solutions were added to 6 mm blank antibiotic discs (BBL) and dried at room temperature to yield 5 mkg/disk. The disks were applied to the inoculated surface of a two-layer agar assay plate (150 mm dia.). The base uninoculated layer contained 42 ml of the supplemented agar selected for the study. The agar selected was TSA containing 16 mkg/ml biotin, sodium chloride. 1.5% (w/v), pH 7.4. The inoculated top layer consisted of 8 ml of the same agar. The final cell count was 6.4 X 10^4 colony-forming units (CFU)/ml of agar. Within 30 min of preparation of the agar plate, disks of each of the test compounds were placed on the agar surface and the plates incubated 48 h at 37.5 °C. The zones of inhibition were measured to the nearest 0.5 mm

Name

Type

Language

TERCONAZOLE

Official Name

English

R-42,470

Code

English

R-42470

Code

English

PIPERAZINE, 1-(4-((2-(2,4-DICHLOROPHENYL)-2-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL)METHOXY)PHENYL)-4-(1-METHYLETHYL)-, CIS

Common Name

English

terconazole [INN]

Common Name

English

TERCONAZOLE [VANDF]

Common Name

English

FUNGISTAT

Brand Name

English

TERCONAZOLE [USP-RS]

Common Name

English

TERMAYAZOLE

Brand Name

English

TRIACONAZOLE

Common Name

English

CIS-1-(P-((2-(2,4-DICHLOROPHENYL)-2-(1H-1,2,4-TRIAZOL-1-YLMETHYL)-1,3-DIOXOLAN-4-YL)METHOXY)PHENYL)-4-ISOPROPYLPIPERAZINE

Common Name

English

TERCONAZOLE [USP MONOGRAPH]

Common Name

English

TERCONAZOLE [EP MONOGRAPH]

Common Name

English

TERCONAZOLE [MART.]

Common Name

English

TERCOSPOR

Brand Name

English

TERAZOL 3

Brand Name

English

R 42470

Code

English

NSC-331942

Code

English

TERCONAZOLE [ORANGE BOOK]

Common Name

English

Terconazole [WHO-DD]

Common Name

English

TERCONAZOLE [USAN]

Common Name

English

TERCONAZOLE [MI]

Common Name

English

TERAZOL

Systematic Name

English

Classification Tree Code System Code

WHO-VATC

QG01AG02