Identification

Name
Ethynodiol diacetate
Accession Number
DB00823  (APRD00760)
Type
Small Molecule
Groups
Approved
Description

A synthetic progestational hormone used alone or in combination with estrogens as an oral contraceptive. Although etynodiol or ethynodiol are sometimes used as a synonym for ethynodiol diacetate, what is usually being referred to is actually ethynodiol diacetate and not ethynodiol (which is a separate drug that has never been marketed, see Ethynodiol).

Structure
Thumb
Synonyms
  • 17α-Ethynyl-19-norandrost-4-ene-3β,17-beta-diol diacetate
  • 17α-Ethynyl-3,17-dihydroxy-4-estrene diacetate
  • 17α-Ethynyl-4-estrene-3β,17β-diol diacetate
  • 17α-Ethynylestr-4-ene-3β,17β-diol acetate
  • 19-Nor-17α-pregn-4-en-20-yne-3β,17-diol diacetate
  • 3β, 17β-Diacetoxy-17α-ethynyl-4-oestrene
  • 3β,17β-Diacetoxy-19-nor-17α-pregn-4-en-20-yne
  • Etynodiol acetate
  • Etynodiol diacetate
External IDs
CB 8080 / SC 11800 / SC-11800
Active Moieties
NameKindUNIICASInChI Key
Ethynodiolprodrug9E01C36A9S1231-93-2JYILPERKVHXLNF-QMNUTNMBSA-N
Product Images
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Demulen 30 (21 Day Pack)Ethynodiol diacetate (2 mg) + Ethinylestradiol (30 mcg)TabletOralPfizer1979-12-31Not applicableCanada
Demulen 30 (28 Day Pack)Ethynodiol diacetate (2 mg) + Ethinylestradiol (30 mcg)TabletOralPfizer1979-12-31Not applicableCanada
Demulen 50 (21 Day Pack)Ethynodiol diacetate (1 mg) + Ethinylestradiol (50 mcg)TabletOralPfizer1970-12-312005-04-01Canada
Demulen 50 (28 Day Pack)Ethynodiol diacetate (1 mg) + Ethinylestradiol (50 mcg)TabletOralPfizer1970-12-312005-04-01Canada
Ethynodiol Diacetate and Ethinyl EstradiolEthynodiol diacetate (1 mg/1) + Ethinylestradiol (50 ug/1)KitMylan Pharmaceuticals2016-11-30Not applicableUs
Ethynodiol Diacetate and Ethinyl EstradiolEthynodiol diacetate (1 mg/1) + Ethinylestradiol (35 ug/1)KitMylan Pharmaceuticals2017-09-19Not applicableUs
Kelnor 1/35Ethynodiol diacetate (1 mg/1) + Ethinylestradiol (35 ug/1)KitPhysicians Total Care, Inc.2008-09-16Not applicableUs00555 9064 58 nlmimage10 0e368734
Kelnor 1/35Ethynodiol diacetate (1 mg/1) + Ethinylestradiol (35 ug/1)KitTeva Pharmaceuticals USA, Inc.2005-06-20Not applicableUs0555 906420180913 8702 rqj9c2
Kelnor 1/35Ethynodiol diacetate (1 mg/1) + Ethinylestradiol (35 ug/1)KitA-S Medication Solutions2005-06-20Not applicableUs
Kelnor 1/50Ethynodiol diacetate (1 mg/1) + Ethinylestradiol (50 ug/1)KitTeva2018-03-01Not applicableUs
International/Other Brands
Conova (Searle) / Continuin / Dernulen (Searle) / Femulen (Pfizer ) / Luteonorm / Luto-Metrodiol / Metrodiol
Categories
UNII
62H10A1236
CAS number
297-76-7
Weight
Average: 384.5085
Monoisotopic: 384.230059512
Chemical Formula
C24H32O4
InChI Key
ONKUMRGIYFNPJW-KIEAKMPYSA-N
InChI
InChI=1S/C24H32O4/c1-5-24(28-16(3)26)13-11-22-21-8-6-17-14-18(27-15(2)25)7-9-19(17)20(21)10-12-23(22,24)4/h1,14,18-22H,6-13H2,2-4H3/t18-,19-,20+,21+,22-,23-,24-/m0/s1
IUPAC Name
(1S,2R,5S,10R,11S,14R,15S)-5-(acetyloxy)-14-ethynyl-15-methyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-14-yl acetate
SMILES
[H][C@@]12CC[C@@](OC(C)=O)(C#C)[C@@]1(C)CC[C@]1([H])[C@@]3([H])CC[C@H](OC(C)=O)C=C3CC[C@@]21[H]

Pharmacology

Indication

For the prevention of pregnancy in women who elect to use this product as a method of contraception.

Associated Conditions
Associated Therapies
Pharmacodynamics

Ethynodiol Diacetate is used as a female contraceptive. Ethynodiol Diacetate is a progestin or a synthetic form of the naturally occurring female sex hormone, progesterone. In a woman's normal menstrual cycle, an egg matures and is released from the ovaries (ovulation). The ovary then produces progesterone, preventing the release of further eggs and priming the lining of the womb for a possible pregnancy. If pregnancy occurs, progesterone levels in the body remain high, maintaining the womb lining. If pregnancy does not occur, progesterone levels in the body fall, resulting in a menstrual period. Ethynodiol Diacetate tricks the body processes into thinking that ovulation has already occurred, by maintaining high levels of the synthetic progesterone. This prevents the release of eggs from the ovaries.

Mechanism of action

Binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like Ethynodiol Diacetate will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.

TargetActionsOrganism
AProgesterone receptor
agonist
Human
AEstrogen receptor alpha
agonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

50-85%

Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe therapeutic efficacy of (R)-warfarin can be increased when used in combination with Ethynodiol diacetate.
(S)-WarfarinThe therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Ethynodiol diacetate.
16-BromoepiandrosteroneThe metabolism of Ethynodiol diacetate can be decreased when combined with 16-Bromoepiandrosterone.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Ethynodiol diacetate.
3,5-diiodothyropropionic acidThe metabolism of Ethynodiol diacetate can be decreased when combined with 3,5-diiodothyropropionic acid.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Ethynodiol diacetate.
4-hydroxycoumarinThe therapeutic efficacy of 4-hydroxycoumarin can be increased when used in combination with Ethynodiol diacetate.
5-androstenedioneThe metabolism of Ethynodiol diacetate can be decreased when combined with 5-androstenedione.
6-Deoxyerythronolide BThe metabolism of Ethynodiol diacetate can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Ethynodiol diacetate.
Food Interactions
Not Available

References

Synthesis Reference

Klimstra, P.D.; U.S. Patent 3,176,013; March 30, 1965; assigned to G.D. Searle & Co.

General References
Not Available
External Links
Human Metabolome Database
HMDB0014961
KEGG Drug
D01294
KEGG Compound
C12724
PubChem Compound
9270
PubChem Substance
46506993
ChemSpider
8913
ChEBI
31580
ChEMBL
CHEMBL1200624
Therapeutic Targets Database
DAP000856
PharmGKB
PA164749157
RxList
RxList Drug Page
Wikipedia
Ethynodiol_diacetate

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedBasic ScienceTherapeutic Equivalency1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Barr Pharmaceuticals
  • Cardinal Health
  • GD Searle LLC
  • Innovative Manufacturing and Distribution Services Inc.
  • Mckesson Corp.
  • Pfizer Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Watson Pharmaceuticals
Dosage forms
FormRouteStrength
TabletOral
Kit
KitOral
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)126-127Klimstra, P.D.; U.S. Patent 3,176,013; March 30, 1965; assigned to G.D. Searle & Co.
logP5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00397 mg/mLALOGPS
logP3.99ALOGPS
logP3.69ChemAxon
logS-5ALOGPS
pKa (Strongest Basic)-6.7ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area52.6 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity106.62 m3·mol-1ChemAxon
Polarizability44.11 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9907
Blood Brain Barrier+0.9399
Caco-2 permeable+0.6125
P-glycoprotein substrateSubstrate0.5754
P-glycoprotein inhibitor IInhibitor0.8432
P-glycoprotein inhibitor IIInhibitor0.619
Renal organic cation transporterNon-inhibitor0.8131
CYP450 2C9 substrateNon-substrate0.8497
CYP450 2D6 substrateNon-substrate0.9139
CYP450 3A4 substrateSubstrate0.7647
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.6524
CYP450 2D6 inhibitorNon-inhibitor0.9519
CYP450 2C19 inhibitorNon-inhibitor0.7671
CYP450 3A4 inhibitorNon-inhibitor0.6564
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8322
Ames testNon AMES toxic0.9651
CarcinogenicityNon-carcinogens0.9119
BiodegradationNot ready biodegradable0.963
Rat acute toxicity2.1783 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9037
hERG inhibition (predictor II)Non-inhibitor0.8353
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

Taxonomy

Description
This compound belongs to the class of organic compounds known as steroid esters. These are compounds containing a steroid moiety which bears a carboxylic acid ester group.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Steroid esters
Direct Parent
Steroid esters
Alternative Parents
Estrane steroids / Delta-4-steroids / Ynones / Dicarboxylic acids and derivatives / Carboxylic acid esters / Acetylides / Organic oxides / Hydrocarbon derivatives
Substituents
Steroid ester / Estrane-skeleton / Delta-4-steroid / Ynone / Dicarboxylic acid or derivatives / Carboxylic acid ester / Acetylide / Carboxylic acid derivative / Organic oxygen compound / Organic oxide
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
terminal acetylenic compound, steroid ester (CHEBI:31580) / C21 steroids (gluco/mineralocorticoids, progestogens) and derivatives (C12724) / C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030124)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. Tamaya T, Nioka S, Furuta N, Shimura T, Takano N: Contribution of functional groups of 19-nor-progestogens to binding to progesterone and estradiol-17beta receptors in rabbit uterus. Endocrinology. 1977 Jun;100(6):1579-84. [PubMed:858280]
  2. Briggs MH: Contraceptive steroid binding to the human uterine progesterone-receptor. Curr Med Res Opin. 1975;3(2):95-8. [PubMed:166800]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
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 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. Kappus H, Bolt HM, Remmer H: Affinity of ethynyl-estradiol and mestranol for the uterine estrogen receptor and for the microsomal mixed function oxidase of the liver. J Steroid Biochem. 1973 Mar;4(2):121-8. [PubMed:4123746]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Gene labs [Link]

Drug created on June 13, 2005 07:24 / Updated on October 11, 2018 22:27