U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C14H13N3
Molecular Weight 223.2731
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of FADROZOLE

SMILES

N#CC1=CC=C(C=C1)C2CCCC3=CN=CN23

InChI

InChIKey=CLPFFLWZZBQMAO-UHFFFAOYSA-N
InChI=1S/C14H13N3/c15-8-11-4-6-12(7-5-11)14-3-1-2-13-9-16-10-17(13)14/h4-7,9-10,14H,1-3H2

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/8595171

Fadrozole (CGS 16949A) is a tetrahydroimidazole-pyridine derivative is a non-steroidal inhibitor of aromatase. In the third phase of clinical trials it was shown, that this drug has good therapeutic effect as a second-line treatment in postmenopausal women with metastatic breast cancer.

Originator

Novartis
177
Curator's Comment: # Novartis

Approval Year

Unknown
149124
Targets

Targets

Primary TargetPharmacologyConditionPotency
Inhibitor
8504
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Phase III
665
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
32.3 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8298071/
12 mg single, oral
dose: 12 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FADROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
27.4 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8298071/
12 mg single, oral
dose: 12 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FADROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
1.5 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8302763/
0.3 mg 2 times / day multiple, oral
dose: 0.3 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FADROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
1.5 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8302763/
1 mg 2 times / day multiple, oral
dose: 1 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FADROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
1.5 ng/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8302763/
2 mg 2 times / day multiple, oral
dose: 2 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FADROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
336 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8298071/
12 mg single, oral
dose: 12 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FADROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
306 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8298071/
12 mg single, oral
dose: 12 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FADROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
10.7 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8302763/
0.3 mg 2 times / day multiple, oral
dose: 0.3 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FADROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
10.5 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8302763/
1 mg 2 times / day multiple, oral
dose: 1 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FADROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
10.7 ng × h/mL
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8302763/
2 mg 2 times / day multiple, oral
dose: 2 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
FADROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.8 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8298071/
12 mg single, oral
dose: 12 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FADROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
2.5 h
EXPERIMENT
https://pubmed.ncbi.nlm.nih.gov/8298071/
12 mg single, oral
dose: 12 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
FADROZOLE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
12 mg single, oral
Highest studied dose
Dose: 12 mg
Route: oral
Route: single
Dose: 12 mg
Sources:
https://pubmed.ncbi.nlm.nih.gov/8298071/
healthy, ADULT
Health Status: healthy
Age Group: ADULT
Sex: M+F
Food Status: FASTED
Sources:
https://pubmed.ncbi.nlm.nih.gov/8298071/
Sources:
https://pubmed.ncbi.nlm.nih.gov/8298071/
2 mg 2 times / day multiple, oral
Highest studied dose
Dose: 2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 2 mg, 2 times / day
Sources:
https://www.ncbi.nlm.nih.gov/pubmed/8595171
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
https://www.ncbi.nlm.nih.gov/pubmed/8595171
Disc. AE: Depression, Lethargy...
AEs leading to
discontinuation/dose reduction:
Depression (grade 3, 3.6%)
Lethargy (grade 3, 3.6%)
Sources:
https://www.ncbi.nlm.nih.gov/pubmed/8595171
1 mg 2 times / day multiple, oral
Studied dose
Dose: 1 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8839901/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/8839901/
Disc. AE: Weakness, Dizziness...
AEs leading to
discontinuation/dose reduction:
Weakness (0.95%)
Dizziness (0.95%)
Sources:
https://pubmed.ncbi.nlm.nih.gov/8839901/
AEs

AEs

AESignificanceDosePopulation
Depression grade 3, 3.6%
Disc. AE
2 mg 2 times / day multiple, oral
Highest studied dose
Dose: 2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 2 mg, 2 times / day
Sources:
https://www.ncbi.nlm.nih.gov/pubmed/8595171
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
https://www.ncbi.nlm.nih.gov/pubmed/8595171
Lethargy grade 3, 3.6%
Disc. AE
2 mg 2 times / day multiple, oral
Highest studied dose
Dose: 2 mg, 2 times / day
Route: oral
Route: multiple
Dose: 2 mg, 2 times / day
Sources:
https://www.ncbi.nlm.nih.gov/pubmed/8595171
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
https://www.ncbi.nlm.nih.gov/pubmed/8595171
Dizziness 0.95%
Disc. AE
1 mg 2 times / day multiple, oral
Studied dose
Dose: 1 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8839901/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/8839901/
Weakness 0.95%
Disc. AE
1 mg 2 times / day multiple, oral
Studied dose
Dose: 1 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1 mg, 2 times / day
Sources:
https://pubmed.ncbi.nlm.nih.gov/8839901/
unhealthy, ADULT
Health Status: unhealthy
Age Group: ADULT
Sex: F
Food Status: UNKNOWN
Sources:
https://pubmed.ncbi.nlm.nih.gov/8839901/
PubMed

PubMed

TitleDatePubMed
Relationship between brain and ovary aromatase activity and isoform-specific aromatase mRNA expression in the fathead minnow (Pimephales promelas).
2006-03-10
Inhibition of human CYP19 by azoles used as antifungal agents and aromatase inhibitors, using a new LC-MS/MS method for the analysis of estradiol product formation.
2006-02-15
Three-dimensional model of cytochrome P450 human aromatase.
2005-12
Zebrafish sex determination and differentiation: involvement of FTZ-F1 genes.
2005-11-10
New aromatase inhibitors as second-line endocrine therapy in postmenopausal patients with metastatic breast carcinoma: a pooled analysis of the randomized trials.
2005-10-01
Extragonadal synthesis of estradiol is protective against kainic acid excitotoxic damage to the hippocampus.
2005-09-28
Cyp2a6 is a principal enzyme involved in hydroxylation of 1,7-dimethylxanthine, a main caffeine metabolite, in humans.
2005-09
Aromatase inhibition abolishes courtship behaviours in the ring dove (Streptopelia risoria) and reduces androgen and progesterone receptors in the hypothalamus and anterior pituitary gland.
2005-08
The adrenocortical tumor cell line NCI-H295R as an in vitro screening system for the evaluation of CYP11B2 (aldosterone synthase) and CYP11B1 (steroid-11beta-hydroxylase) inhibitors.
2005-08
Estrogen provision by reactive glia decreases apoptosis in the zebra finch (Taeniopygia guttata).
2005-08
Evidence that estrogen regulates the sex change of honeycomb grouper (Epinephelus merra), a protogynous hermaphrodite fish.
2005-06-01
Synthesis and evaluation of imidazolylmethylenetetrahydronaphthalenes and imidazolylmethyleneindanes: potent inhibitors of aldosterone synthase.
2005-03-24
Synthesis and evaluation of (pyridylmethylene)tetrahydronaphthalenes/-indanes and structurally modified derivatives: potent and selective inhibitors of aldosterone synthase.
2005-03-10
Enantiomeric resolution of new aromatase inhibitors by liquid chromatography on cellulose chiral stationary phases.
2005-03
Antiandrogenic effects in short-term in vivo studies of the fungicide fenarimol.
2005-02-01
Effects of sex steroids and their inhibitors on endocrine parameters and gender growth differences in Eurasian perch (Perca fluviatilis) juveniles.
2005-02
Co-culture of primary human mammary fibroblasts and MCF-7 cells as an in vitro breast cancer model.
2005-02
Dehydroepiandrosterone regulates astroglia reaction to denervation of olfactory glomeruli.
2004-11-15
Evidence for concurrent effects of exposure to environmental cadmium and lead on hepatic CYP2A6 phenotype and renal function biomarkers in nonsmokers.
2004-11
Successful detection of (anti-)androgenic and aromatase inhibitors in pre-spawning adult fathead minnows (Pimephales promelas) using easily measured endpoints of sexual development.
2004-10-18
Effects of estrogens during embryonal development on crowing in the domestic fowl.
2004-09-30
Combined effect of testosterone and apocynin on nitric oxide and superoxide production in PMA-differentiated THP-1 cells.
2004-09-17
Glial aromatization decreases neural injury in the zebra finch (Taeniopygia guttata): influence on apoptosis.
2004-08
Differential expression pattern and steroid hormone sensitivity of SNAP-25 and synaptoporin mRNA in the telencephalic song control nucleus HVC of the zebra finch.
2004-07-12
Modulation by steroid hormones of a "sexy" acoustic signal in an Oscine species, the Common Canary Serinus canaria.
2004-06
Effects of follicle stimulating hormone on estradiol-17 beta production and P-450 aromatase (CYP19) activity and mRNA expression in brown trout vitellogenic ovarian follicles in vitro.
2004-06
Aromatase inhibition in the treatment of advanced breast cancer: is there a relationship between potency and clinical efficacy?
2004-05-04
Aromatase modulation alters gonadal differentiation in developing zebrafish (Danio rerio).
2004-04-14
Characterization of stable human aromatase expressed in E. coli.
2004-04
Expression of aromatase mRNA and effects of aromatase inhibitor during ovarian development in the medaka, Oryzias latipes.
2004-03-01
Fulvestrant is an effective and well-tolerated endocrine therapy for postmenopausal women with advanced breast cancer: results from clinical trials.
2004-03
Sex inversion of sexually immature honeycomb grouper (Epinephelus merra) by aromatase inhibitor.
2004-03
Aromatase inhibitor induces complete sex change in the protogynous honeycomb grouper (Epinephelus merra).
2004-03
Expression of androgen receptor mRNA in zebra finch song system: developmental regulation by estrogen.
2004-02-16
Presynaptic N-methyl-D-aspartate receptor expression is increased by estrogen in an aromatase-rich area of the songbird hippocampus.
2004-02-16
The effects of the aromatase inhibitor fadrozole hydrochloride on fetuses and uteri in late pregnant rats.
2004-02
A comparison of human H295R and rat R2C cell lines as in vitro screening tools for effects on aromatase.
2004-01-15
First-line endocrine treatment of breast cancer: aromatase inhibitor or antioestrogen?
2004-01-12
An aromatase inhibitor or high water temperature induce oocyte apoptosis and depletion of P450 aromatase activity in the gonads of genetic female zebrafish during sex-reversal.
2004-01
Endocrinology and hormone therapy in breast cancer: aromatase inhibitors versus antioestrogens.
2004
Lack of efficacy of fadrozole in treating precocious puberty in girls with the McCune-Albright syndrome.
2003-12
Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection.
2003-09-24
Neuroprotection by the steroids pregnenolone and dehydroepiandrosterone is mediated by the enzyme aromatase.
2003-09-15
Effect of non-steroidal aromatase inhibitor on blood plasma ovarian steroid and thyroid hormones in laying hen (Gallus domesticus).
2003-09
Role of aromatization in anticipatory and consummatory aspects of sexual behavior in male rats.
2003-08
Applicability of the intratumor aromatase preclinical model to predict clinical trial results with endocrine therapy.
2003-08
Degree of sex reversal as related to plasma steroid levels in genetic female chickens (Gallus domesticus) treated with Fadrozole.
2003-08
Delayed implantation induced by fadrozole hydrochloride in rats.
2003-07
Induction of XY sex reversal by estrogen involves altered gene expression in a teleost, tilapia.
2003
A study of fadrozole, a new aromatase inhibitor, in postmenopausal women with advanced metastatic breast cancer.
1992-01
Patents

Patents

04728645
5
JP2002535635A
5
JP2006306872A
3
JP2006524634A
46

Sample Use Guides

In Vivo Use Guide
0.5, 1.0 or 2.0 mg orally b.d.
Route of Administration: Oral
In Vitro Use Guide
CGS-16949A (fadrozole) blocked aromatase by 50% in human breast cancer homogenates, live breast cancer cells, human placental microsomes and porcine ovarian microsomes at concentrations of 0.008 to 0.02 microM
Name Type Language
(±)-P-(5,6,7,8-TETRAHYDROIMIDAZO(1,5-A)PYRIDIN-5-YL)BENZONITRILE
Preferred Name English
FADROZOLE
INN   MI   WHO-DD  
INN  
Official Name English
fadrozole [INN]
Common Name English
Fadrozole [WHO-DD]
Common Name English
BENZONITRILE, 4-(5,6,7,8-TETRAHYDROIMIDAZO(1,5-A)PYRIDIN-5-YL)-, (±)-
Systematic Name English
FADROZOLE [MI]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2018
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
Code System Code Type Description
IUPHAR
8311
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
FDA UNII
H3988M64PU
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
MESH
D017316
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
EVMPD
SUB07497MIG
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
EPA CompTox
DTXSID5034141
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
NCI_THESAURUS
C79911
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
PUBCHEM
59693
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
INN
6632
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
CAS
102676-47-1
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
SMS_ID
100000081551
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
DRUG CENTRAL
1126
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
MERCK INDEX
m5238
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY Merck Index
ChEMBL
CHEMBL9298
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
WIKIPEDIA
FADROZOLE
Created by admin on Mon Mar 31 18:22:41 GMT 2025 , Edited by admin on Mon Mar 31 18:22:41 GMT 2025
PRIMARY
ACTIVE MOIETY
Structure of FADROZOLE
SALT/SOLVATE (PARENT)
Structure of FADROZOLE HYDROCHLORIDE
NIH
NCATS
PRIVACY NOTICE
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966