Identification

Name
Quinestrol
Accession Number
DB04575
Type
Small Molecule
Groups
Approved
Description

The 3-cyclopentyl ether of ethinyl estradiol.

Structure
Thumb
Synonyms
  • 17-alpha-Ethinylestradiol 3-cyclopentyl ether
  • 17alpha-Ethynylestradiol 3-cyclopentyl ether
  • Eston
  • Estradiol-17-beta 3-cyclopentyl ether
  • Estrovis
  • Estrovis 4000
  • Estrovister
  • ethinyl estradiol 3-cyclopentyl ether
  • Plestrovis
  • Quilea
  • Quinestrol
  • Quinestrolo
  • Quinestrolum
External IDs
W 3566 / W-3566
International/Other Brands
Estrovis
Categories
UNII
JR0N7XD5GZ
CAS number
152-43-2
Weight
Average: 364.5204
Monoisotopic: 364.240230268
Chemical Formula
C25H32O2
InChI Key
PWZUUYSISTUNDW-VAFBSOEGSA-N
InChI
InChI=1S/C25H32O2/c1-3-25(26)15-13-23-22-10-8-17-16-19(27-18-6-4-5-7-18)9-11-20(17)21(22)12-14-24(23,25)2/h1,9,11,16,18,21-23,26H,4-8,10,12-15H2,2H3/t21-,22-,23+,24+,25+/m1/s1
IUPAC Name
(1S,10R,11S,14R,15S)-5-(cyclopentyloxy)-14-ethynyl-15-methyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadeca-2(7),3,5-trien-14-ol
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]1([H])C3=C(CC[C@@]21[H])C=C(OC1CCCC1)C=C3

Pharmacology

Indication

Used in hormone replacement therapy, treating symptoms of menopause such as hot flashes. Also used to treat breast and prostate cancer.

Pharmacodynamics

Quinestrol is the 3-cyclopentyl ether of ethinyl estradiol (the active metabolite). After gastrointestinal absorption, it is stored in adipose tissue where it is slowly released and metabolized principally to the parent compound, ethinyl estradiol. Ethinyl estradiol is a synthetic derivative of the natural estrogen estradiol.

Mechanism of action

Estrogens diffuse into their target cells and interact with a protein receptor (the estrogen receptor). Estrogen interacts with a target cell receptor. When the estrogen receptor has bound its ligand it can enter the nucleus of the target cell, and regulate gene transcription which leads to formation of messenger RNA. The mRNA interacts with ribosomes to produce specific proteins that express the effect of estradiol upon the target cell. 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. Target cells include 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. The combination of an estrogen with a progestin suppresses the hypothalamic-pituitary system, decreasing the secretion of gonadotropin-releasing hormone (GnRH).

TargetActionsOrganism
AEstrogen receptor alpha
agonist
modulator
Human
Absorption

Absorbed following oral administration.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Metabolized principally to the parent compound, ethinyl estradiol. Ethinyl estradiol is metabolized in the liver. Quantitatively, the major metabolic pathway for ethinyl estradiol, both in rats and in humans, is aromatic hydroxylation, as it is for the natural estrogens.

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Symptoms of overdose include nausea and vomiting, and withdrawal bleeding may occur in females.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
16-BromoepiandrosteroneThe serum concentration of 16-Bromoepiandrosterone can be increased when it is combined with Quinestrol.
19-norandrostenedioneThe serum concentration of 19-norandrostenedione can be increased when it is combined with Quinestrol.
5-androstenedioneThe serum concentration of 5-androstenedione can be increased when it is combined with Quinestrol.
AbciximabQuinestrol may decrease the anticoagulant activities of Abciximab.
AceclofenacAceclofenac may increase the thrombogenic activities of Quinestrol.
AcenocoumarolQuinestrol may decrease the anticoagulant activities of Acenocoumarol.
Acetylsalicylic acidQuinestrol may decrease the anticoagulant activities of Acetylsalicylic acid.
AldosteroneThe serum concentration of Aldosterone can be increased when it is combined with Quinestrol.
AlemtuzumabQuinestrol may increase the thrombogenic activities of Alemtuzumab.
AlteplaseQuinestrol may decrease the anticoagulant activities of Alteplase.
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015579
KEGG Drug
D00576
KEGG Compound
C07619
PubChem Compound
9046
PubChem Substance
46508939
ChemSpider
8694
ChEBI
8716
ChEMBL
CHEMBL1201165
Therapeutic Targets Database
DAP001016
PharmGKB
PA164749042
Wikipedia
Quinestrol

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)107.5 °CPhysProp
Predicted Properties
PropertyValueSource
Water Solubility0.00157 mg/mLALOGPS
logP5.19ALOGPS
logP5.4ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)17.59ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area29.46 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity108.27 m3·mol-1ChemAxon
Polarizability44.02 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.997
Blood Brain Barrier+0.9483
Caco-2 permeable+0.8214
P-glycoprotein substrateSubstrate0.6542
P-glycoprotein inhibitor INon-inhibitor0.585
P-glycoprotein inhibitor IINon-inhibitor0.8718
Renal organic cation transporterNon-inhibitor0.8168
CYP450 2C9 substrateNon-substrate0.7004
CYP450 2D6 substrateNon-substrate0.9177
CYP450 3A4 substrateSubstrate0.7205
CYP450 1A2 substrateInhibitor0.8321
CYP450 2C9 inhibitorNon-inhibitor0.8873
CYP450 2D6 inhibitorNon-inhibitor0.9494
CYP450 2C19 inhibitorInhibitor0.7307
CYP450 3A4 inhibitorNon-inhibitor0.5178
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.73
Ames testNon AMES toxic0.9105
CarcinogenicityNon-carcinogens0.8635
BiodegradationNot ready biodegradable0.9812
Rat acute toxicity1.9408 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8631
hERG inhibition (predictor II)Inhibitor0.5854
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a59-2920000000-99119dee5db3aab05906

Taxonomy

Description
This compound belongs to the class of organic compounds known as estrane steroids. These are steroids with a structure based on the estrane skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Estrane steroids
Direct Parent
Estrane steroids
Alternative Parents
17-hydroxysteroids / Phenanthrenes and derivatives / Tetralins / Alkyl aryl ethers / Ynones / Tertiary alcohols / Cyclic alcohols and derivatives / Acetylides / Hydrocarbon derivatives
Substituents
Estrane-skeleton / Hydroxysteroid / 17-hydroxysteroid / Phenanthrene / Tetralin / Alkyl aryl ether / Benzenoid / Ynone / Tertiary alcohol / Cyclic alcohol
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
terminal acetylenic compound, 17-hydroxy steroid (CHEBI:8716) / C18 steroids (estrogens) and derivatives (C07619) / C18 steroids (estrogens) and derivatives (LMST02010037)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
Modulator
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 tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  4. Shyu C, Cavileer TD, Nagler JJ, Ytreberg FM: Computational estimation of rainbow trout estrogen receptor binding affinities for environmental estrogens. Toxicol Appl Pharmacol. 2011 Feb 1;250(3):322-6. doi: 10.1016/j.taap.2010.11.005. Epub 2010 Nov 12. [PubMed:21075131]

Drug created on September 07, 2007 15:29 / Updated on October 01, 2018 13:52