Norethynodrel
Norethynodrel (NOR) is a synthetic progestogen used in hormonal contraceptives and for the treatment of gynecological disorders. It is generally no longer used. It is a prodrug of norethindrone (NET), although NET is only a minor metabolite of NOR.
Tags
Approvals
US FDA-Approved
Identifiers
Abbreviation
NOR (Jin et al.), NED (Kubli-Garfias et al.)
References
- Jin, Y., Duan, L., Chen, M., Penning, T. M., & Kloosterboer, H. (2012). Metabolism of the synthetic progestogen norethynodrel by human ketosteroid reductases of the aldo-keto reductase superfamily. Journal of Steroid Biochemistry and Molecular Biology, 129(3–5), 139–144. (View all citations for this reference)
- Kubli-Garfias, C.; González-Flores, O.; Gómora-Arrati, P.; González-Mariscal, G.; Vázquez-Ramírez, R.; Beyer, C. Bimodal Binding and Free Energy of the Progesterone Receptor in the Induction of Female Sexual Receptivity by Progesterone and Synthetic Progestins. J. Steroid Biochem. Mol. Biol. 2013, 133, 43–50. (View all citations for this reference)
Names
- Noretynodrel
- NSC-15432
- 17α-ethynyl-17β-hydroxy-5(10)-estren-3-one
References
- Wikipedia: Noretynodrel (View all citations for this reference)
- Jin, Y., Duan, L., Chen, M., Penning, T. M., & Kloosterboer, H. (2012). Metabolism of the synthetic progestogen norethynodrel by human ketosteroid reductases of the aldo-keto reductase superfamily. Journal of Steroid Biochemistry and Molecular Biology, 129(3–5), 139–144. (View all citations for this reference)
CASRN
68-23-5
References
PubChem CID
6231
ECHA InfoCard
- 100.000.620
- EC / List #: 200-682-1
UNII
88181ACA0M
Wikipedia Entry Name
Noretynodrel
ChEMBL ID
CHEMBL1387
ChemSpider ID
5995
NIST
Norethynodrel
ATC Code(s)
Physical & Chemical Properties
Molecular Formula
C20H26O2
References
Molecular Weight
298.419 g/mol
References
Appearance
White, odorless, crystalline powder.
References
- WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
- Toxnet: Norethynodrel (View all citations for this reference)
Melting Point
169.5° C
References
- ChemIDPlus: A Toxnet Database. Norethynodrel. (View all citations for this reference)
- WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
- Toxnet: Norethynodrel (View all citations for this reference)
Solubility
Very slightly soluble in water, freely soluble in chloroform, soluble in acetone, sparingly soluble in ethanol.
Specific Optical Rotation
+108° in 1% chloroform
References
- WHO International Agency for Research on Cancer: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Volume 91: Combined Estrogen-Progestogen Contraceptives and Combined Estrogen-Progestogen Menopausal Therapy. 2007, Lyon, France. (View all citations for this reference)
- Toxnet: Norethynodrel (View all citations for this reference)
Toxicology
GHS Hazard Code(s)
| Class | Category | Code | Description |
|---|---|---|---|
| Carcinogenicity | 1B | H350 | May cause cancer |
| Reproductive Toxicity | 1B | H360 | May damage fertility or the unborn child |
Mutagenicity
Not found to be mutagenic in the Ames Salmonella/microsome direct plate incorporation protocol.
References
- Lang, R.; Reimann, R. Studies for a Genotoxic Potential of Some Endogenous and Exogenous Sex Steroids. I. Communication: Examination for the Induction of Gene Mutations Using the Ames Salmonella/microsome Test and the HGPRT Test in V79 Cells. Environ. Mol. Mutagen. 1993, 21 (3), 272–304. (View all citations for this reference)
Genotoxicity
Found to be genotoxic to human lymphocytes at 60 μg/mL in the presence of metabolic activation (S9 mix), as measured by chromosomal aberrations, sister chromatid exchanges, and replication index.
TD50
mouse: 0.279 mg/kg/day (In Enovid (mestranol/norethynodrel) formulation)
MRTD
0.667 mg/kg/day
Biochemistry & Pharmacology
Progesterone Receptor Activity
Agonist
Estrogen Receptor Activity
Agonist.
References
- Jin, Y., Duan, L., Chen, M., Penning, T. M., & Kloosterboer, H. (2012). Metabolism of the synthetic progestogen norethynodrel by human ketosteroid reductases of the aldo-keto reductase superfamily. Journal of Steroid Biochemistry and Molecular Biology, 129(3–5), 139–144. (View all citations for this reference)
Serum Protein Binding
94-95% bound. Evidence points towards a specific protein that is not CBG, SHBG, or albumin.
Clearance
30 L/day
Indications
For the prevention of pregnancy.
Metabolites
Name
Structure
Notes
US FDA-Approved Products
Name
Formulation
Status
ANDA #
Discontinued
010976