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Identification
NameChlorotrianisene
Accession NumberDB00269  (APRD00715)
TypeSmall Molecule
GroupsWithdrawn
Description

A powerful synthetic, non-steroidal estrogen. [PubChem]

Structure
Thumb
Synonyms
Chloortrianisestrol
Chlorestrolo
Chlorotrianisenum
Chlorotrianisine
Chlorotrianizen
Chlortrianisen
Chlortrianisestrol
Chlortrianisoestrolum
Chlortrianizen
Clorotrianiseno
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
MerbentulMerrell
TaceMerrell
Tace FNMerrell
TriagenGentili
Brand mixturesNot Available
SaltsNot Available
Categories
UNII6V5034L121
CAS number569-57-3
WeightAverage: 380.864
Monoisotopic: 380.117922245
Chemical FormulaC23H21ClO3
InChI KeyInChIKey=BFPSDSIWYFKGBC-UHFFFAOYSA-N
InChI
InChI=1S/C23H21ClO3/c1-25-19-10-4-16(5-11-19)22(17-6-12-20(26-2)13-7-17)23(24)18-8-14-21(27-3)15-9-18/h4-15H,1-3H3
IUPAC Name
1-[1-chloro-2,2-bis(4-methoxyphenyl)ethenyl]-4-methoxybenzene
SMILES
COC1=CC=C(C=C1)C(Cl)=C(C1=CC=C(OC)C=C1)C1=CC=C(OC)C=C1
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as stilbenes. These are organic compounds containing a 1,2-diphenylethylene moiety. Stilbenes (C6-C2-C6 ) are derived from the common phenylpropene (C6-C3) skeleton building block. The introduction of one or more hydroxyl groups to a phenyl ring lead to stilbenoids.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassStilbenes
Sub ClassNot Available
Direct ParentStilbenes
Alternative Parents
Substituents
  • Stilbene
  • Diphenylmethane
  • Phenylpropene
  • Methoxybenzene
  • Phenol ether
  • Anisole
  • Alkyl aryl ether
  • Benzenoid
  • Monocyclic benzene moiety
  • Chloroalkene
  • Haloalkene
  • Vinyl halide
  • Vinyl chloride
  • Ether
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organochloride
  • Organohalogen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationUsed to treat symptoms of menopause, deficiencies in ovary function (including underdevelopment of female sexual characteristics and some types of infertility), and in rare cases, prostate cancer. Chlorotrianisene may also be used to prevent breast engorgement following childbirth.
PharmacodynamicsChlorotrianisene is a nonsteroidal synthetic estrogen. After menopause, when the body no longer produces estrogen, chlorotrianisene is used as a simple replacement of estrogen. The estrogen-stimulated endometrium may bleed within 48-72 hours after discontinuance of estrogen therapy. Paradoxically, prolonged estrogen therapy may cause shrinkage of the endometrium and an increase in size of the myometrium. Estrogens have a weak anabolic effect and may cause sodium retention with associated fluid retention and edema. Estrogens may also decrease elevated blood cholesterol and phospholipid concentrations. Estrogens affect bone by increasing calcium deposition and accelerating epiphyseal closure, following initial growth stimulation. During the preovulatory or nonovulatory phase of the menstrual cycle, estrogen is the principal determinant in the onset of menstruation. A decline of estrogenic activity at the end of the menstrual cycle also may induce menstruation; however, the cessation of progesterone secretion is the most important factor during the mature ovulatory phase of the menstrual cycle. The benefit derived from estrogen therapy in the prevention of postpartum breast engorgement must be carefully weighed against the potential increased risk of puerperal thromboembolism associated with the use of large doses of estrogens.
Mechanism of actionChlorotrianisene binds to the estrogen receptor on various estrogen receptor bearing cells. Target cells include cells in the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Estrogens increase the hepatic synthesis of sex hormone binding globulin (SHBG), thyroid-binding globulin (TBG), and other serum proteins and suppress follicle-stimulating hormone (FSH) from the anterior pituitary.
Related Articles
AbsorptionAbsorption following oral administration is rapid.
Volume of distributionNot Available
Protein binding50-80%
Metabolism

Metabolized principally in the liver, although the kidneys, gonads, and muscle tissues may be involved to some extent. The metabolic fate of the synthetic estrogens has not been fully elucidated.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityAcute overdosage of large doses of oral contraceptives in chidren reportedly produces almost no toxicity except nausea and vomiting. Acute overdosage of estrogens may cause nausea, and withdrawal bleeding may occur in females.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.651
Caco-2 permeable+0.8218
P-glycoprotein substrateNon-substrate0.6283
P-glycoprotein inhibitor IInhibitor0.5266
P-glycoprotein inhibitor IINon-inhibitor0.8382
Renal organic cation transporterNon-inhibitor0.8102
CYP450 2C9 substrateNon-substrate0.7764
CYP450 2D6 substrateNon-substrate0.8599
CYP450 3A4 substrateSubstrate0.6053
CYP450 1A2 substrateNon-inhibitor0.8094
CYP450 2C9 inhibitorNon-inhibitor0.907
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.5072
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.8625
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.6402
BiodegradationNot ready biodegradable0.9562
Rat acute toxicity1.9303 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8429
hERG inhibition (predictor II)Non-inhibitor0.8456
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Banner pharmacaps inc
  • Sanofi aventis us llc
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point113-114REM p.988 Shelton, R.S. and Van Campen, M.G. Jr.; U S . Patent 2,430,891; November 18,1947; assigned to the Wm. S. Merrell Company.
logP6.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000199 mg/mLALOGPS
logP5.95ALOGPS
logP5.43ChemAxon
logS-6.3ALOGPS
pKa (Strongest Basic)-4.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area27.69 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity119.17 m3·mol-1ChemAxon
Polarizability41.6 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis Reference

Shelton, R.S. and Van Campen, M.G. Jr.; U S . Patent 2,430,891; November 18,1947; assigned to the Wm. S. Merrell Company.

General ReferencesNot Available
External Links
ATC CodesG03CA06
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolChlorotrianisene may decrease the anticoagulant activities of Acenocoumarol.
AcetaminophenThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Acetaminophen.
AcitretinThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Acitretin.
AlitretinoinThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Alitretinoin.
AminophyllineThe serum concentration of Aminophylline can be increased when it is combined with Chlorotrianisene.
AmobarbitalThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Amobarbital.
AnastrozoleThe therapeutic efficacy of Anastrozole can be decreased when used in combination with Chlorotrianisene.
Anthrax immune globulinChlorotrianisene may increase the thrombogenic activities of Anthrax immune globulin.
ApixabanChlorotrianisene may decrease the anticoagulant activities of Apixaban.
AprepitantThe serum concentration of Chlorotrianisene can be decreased when it is combined with Aprepitant.
ArgatrobanChlorotrianisene may decrease the anticoagulant activities of Argatroban.
ArmodafinilThe serum concentration of Chlorotrianisene can be decreased when it is combined with Armodafinil.
ArtemetherThe serum concentration of Chlorotrianisene can be decreased when it is combined with Artemether.
AtazanavirThe serum concentration of Chlorotrianisene can be decreased when it is combined with Atazanavir.
BetamethasoneThe serum concentration of Betamethasone can be increased when it is combined with Chlorotrianisene.
BexaroteneThe serum concentration of Chlorotrianisene can be decreased when it is combined with Bexarotene.
BivalirudinChlorotrianisene may decrease the anticoagulant activities of Bivalirudin.
BoceprevirThe serum concentration of Chlorotrianisene can be decreased when it is combined with Boceprevir.
BosentanThe serum concentration of Chlorotrianisene can be decreased when it is combined with Bosentan.
ButabarbitalThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Butabarbital.
ButalbitalThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Butalbital.
CaffeineThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Caffeine.
CarbamazepineThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Carbamazepine.
CelecoxibCelecoxib may increase the thrombogenic activities of Chlorotrianisene.
CholestyramineThe serum concentration of Chlorotrianisene can be decreased when it is combined with Cholestyramine.
ClobazamThe serum concentration of Chlorotrianisene can be decreased when it is combined with Clobazam.
CobicistatThe serum concentration of Chlorotrianisene can be decreased when it is combined with Cobicistat.
ColesevelamThe serum concentration of Chlorotrianisene can be decreased when it is combined with Colesevelam.
ColestipolThe serum concentration of Chlorotrianisene can be decreased when it is combined with Colestipol.
CorticotropinThe serum concentration of Corticotropin can be increased when it is combined with Chlorotrianisene.
Cortisone acetateThe serum concentration of Cortisone acetate can be increased when it is combined with Chlorotrianisene.
Dabigatran etexilateChlorotrianisene may decrease the anticoagulant activities of Dabigatran etexilate.
DabrafenibThe serum concentration of Chlorotrianisene can be decreased when it is combined with Dabrafenib.
DalteparinChlorotrianisene may decrease the anticoagulant activities of Dalteparin.
DanaparoidChlorotrianisene may decrease the anticoagulant activities of Danaparoid.
DarunavirThe serum concentration of Chlorotrianisene can be decreased when it is combined with Darunavir.
DesirudinChlorotrianisene may decrease the anticoagulant activities of Desirudin.
DexamethasoneThe serum concentration of Dexamethasone can be increased when it is combined with Chlorotrianisene.
EdoxabanChlorotrianisene may decrease the anticoagulant activities of Edoxaban.
ElvitegravirThe serum concentration of Chlorotrianisene can be decreased when it is combined with Elvitegravir.
EnoxaparinChlorotrianisene may decrease the anticoagulant activities of Enoxaparin.
Eslicarbazepine acetateThe serum concentration of Chlorotrianisene can be decreased when it is combined with Eslicarbazepine acetate.
ExemestaneThe therapeutic efficacy of Exemestane can be decreased when used in combination with Chlorotrianisene.
ExenatideThe serum concentration of Chlorotrianisene can be decreased when it is combined with Exenatide.
FelbamateThe serum concentration of Chlorotrianisene can be decreased when it is combined with Felbamate.
FlibanserinThe serum concentration of Flibanserin can be increased when it is combined with Chlorotrianisene.
FludrocortisoneThe serum concentration of Fludrocortisone can be increased when it is combined with Chlorotrianisene.
Fondaparinux sodiumChlorotrianisene may decrease the anticoagulant activities of Fondaparinux sodium.
FosamprenavirThe serum concentration of Chlorotrianisene can be decreased when it is combined with Fosamprenavir.
FosaprepitantThe serum concentration of Chlorotrianisene can be decreased when it is combined with Fosaprepitant.
FosphenytoinThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Fosphenytoin.
GriseofulvinThe metabolism of Chlorotrianisene can be increased when combined with Griseofulvin.
HeparinChlorotrianisene may decrease the anticoagulant activities of Heparin.
HyaluronidaseThe therapeutic efficacy of Hyaluronidase can be decreased when used in combination with Chlorotrianisene.
HydrocortisoneThe serum concentration of Hydrocortisone can be increased when it is combined with Chlorotrianisene.
IsotretinoinThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Isotretinoin.
LamotrigineThe serum concentration of Lamotrigine can be decreased when it is combined with Chlorotrianisene.
LenalidomideChlorotrianisene may increase the thrombogenic activities of Lenalidomide.
LevothyroxineThe therapeutic efficacy of Levothyroxine can be decreased when used in combination with Chlorotrianisene.
LiothyronineThe therapeutic efficacy of Liothyronine can be decreased when used in combination with Chlorotrianisene.
LiotrixThe therapeutic efficacy of Liotrix can be decreased when used in combination with Chlorotrianisene.
LopinavirThe serum concentration of Chlorotrianisene can be decreased when it is combined with Lopinavir.
LumefantrineThe serum concentration of Chlorotrianisene can be decreased when it is combined with Lumefantrine.
MethohexitalThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Methohexital.
MethylprednisoloneThe serum concentration of Methylprednisolone can be increased when it is combined with Chlorotrianisene.
MetreleptinThe serum concentration of Chlorotrianisene can be decreased when it is combined with Metreleptin.
MifepristoneThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Mifepristone.
ModafinilThe serum concentration of Chlorotrianisene can be decreased when it is combined with Modafinil.
Mycophenolate mofetilThe serum concentration of Chlorotrianisene can be decreased when it is combined with Mycophenolate mofetil.
Mycophenolic acidThe serum concentration of Chlorotrianisene can be decreased when it is combined with Mycophenolic acid.
NadroparinChlorotrianisene may decrease the anticoagulant activities of Nadroparin.
NafcillinThe metabolism of Chlorotrianisene can be increased when combined with Nafcillin.
NelfinavirThe serum concentration of Chlorotrianisene can be decreased when it is combined with Nelfinavir.
NevirapineThe serum concentration of Chlorotrianisene can be decreased when it is combined with Nevirapine.
OspemifeneThe risk or severity of adverse effects can be increased when Chlorotrianisene is combined with Ospemifene.
OxcarbazepineThe serum concentration of Chlorotrianisene can be decreased when it is combined with Oxcarbazepine.
PentobarbitalThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Pentobarbital.
PhenobarbitalThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Phenobarbital.
PhenytoinThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Phenytoin.
PrednisoloneThe serum concentration of Prednisolone can be increased when it is combined with Chlorotrianisene.
PrednisoneThe serum concentration of Prednisone can be increased when it is combined with Chlorotrianisene.
PrucaloprideThe serum concentration of Chlorotrianisene can be decreased when it is combined with Prucalopride.
Repository corticotropinThe serum concentration of Repository corticotropin can be increased when it is combined with Chlorotrianisene.
RifabutinThe serum concentration of Chlorotrianisene can be decreased when it is combined with Rifabutin.
RifampicinThe serum concentration of Chlorotrianisene can be decreased when it is combined with Rifampicin.
RifapentineThe serum concentration of Chlorotrianisene can be decreased when it is combined with Rifapentine.
RitonavirThe serum concentration of Chlorotrianisene can be decreased when it is combined with Ritonavir.
RivaroxabanChlorotrianisene may decrease the anticoagulant activities of Rivaroxaban.
RopiniroleThe serum concentration of Ropinirole can be increased when it is combined with Chlorotrianisene.
SaquinavirThe serum concentration of Chlorotrianisene can be decreased when it is combined with Saquinavir.
SecobarbitalThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Secobarbital.
SelegilineThe serum concentration of Selegiline can be increased when it is combined with Chlorotrianisene.
TelaprevirThe serum concentration of Chlorotrianisene can be decreased when it is combined with Telaprevir.
ThalidomideChlorotrianisene may increase the thrombogenic activities of Thalidomide.
TheophyllineThe serum concentration of Theophylline can be increased when it is combined with Chlorotrianisene.
Thyroid, porcineThe therapeutic efficacy of Thyroid extract can be decreased when used in combination with Chlorotrianisene.
TinzaparinChlorotrianisene may decrease the anticoagulant activities of Tinzaparin.
TipranavirChlorotrianisene may increase the dermatologic adverse activities of Tipranavir.
TopiramateThe serum concentration of Chlorotrianisene can be decreased when it is combined with Topiramate.
Tranexamic AcidChlorotrianisene may increase the thrombogenic activities of Tranexamic Acid.
TretinoinThe therapeutic efficacy of Chlorotrianisene can be decreased when used in combination with Tretinoin.
TriamcinoloneThe serum concentration of Triamcinolone can be increased when it is combined with Chlorotrianisene.
Ursodeoxycholic acidThe therapeutic efficacy of Ursodeoxycholic acid can be decreased when used in combination with Chlorotrianisene.
Vitamin CThe serum concentration of Chlorotrianisene can be increased when it is combined with Vitamin C.
VoriconazoleThe metabolism of Chlorotrianisene can be decreased when combined with Voriconazole.
WarfarinChlorotrianisene may decrease the anticoagulant activities of Warfarin.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription fact...
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
References
  1. Kupfer D, Bulger WH: Inactivation of the uterine estrogen receptor binding of estradiol during P-450 catalyzed metabolism of chlorotrianisene (TACE). Speculation that TACE antiestrogenic activity involves covalent binding to the estrogen receptor. FEBS Lett. 1990 Feb 12;261(1):59-62. [PubMed:2307235 ]
  2. Jordan VC, Gosden B: Inhibition of the uterotropic activity of estrogens and antiestrogens by the short acting antiestrogen LY117018. Endocrinology. 1983 Aug;113(2):463-8. [PubMed:6872937 ]
  3. Wang JY, Xu BH, Tian LJ, Wang Y: [Clinical characteristics and potential prognostic factors of breast cancer patients with liver metastases]. Zhonghua Zhong Liu Za Zhi. 2006 Aug;28(8):612-6. [PubMed:17236558 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inducer
General Function:
Oxygen binding
Specific Function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular Weight:
57882.48 Da
References
  1. Adashi EY, Hsueh AJ: Estrogens augment the stimulation of ovarian aromatase activity by follicle-stimulating hormone in cultured rat granulosa cells. J Biol Chem. 1982 Jun 10;257(11):6077-83. [PubMed:6804461 ]
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Drug created on June 13, 2005 07:24 / Updated on April 04, 2014 10:46