Dimethandrolone

This article is about a non-clinically used compound. For the experimental contraceptive, see Dimethandrolone undecanoate.

Dimethandrolone

Clinical data
Other names	CDB-1321; Dimethylnandrolone; 7α,11β-Dimethyl-19-nortestosterone; 7α,11β-Dimethylestr-4-en-17β-ol-3-one; 7α,11β-Dimethyl-19-norandrost-4-en-17β-ol-3-one
Routes of administration	By mouth
Drug class	Androgen; Anabolic steroid; Progestogen
Identifiers
IUPAC name (7R,8R,9S,10R,11S,13S,14S,17S)-17-hydroxy-7,11,13-trimethyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-one
CAS Number	226066-52-0 366472-45-9 (undecanoate)
PubChem CID	9882863
ChemSpider	8058538
UNII	OD742D6TJ9
Chemical and physical data
Formula	C20H30O2
Molar mass	302.458 g·mol−1
3D model (JSmol)	Interactive image
SMILES CC1CC2=CC(=O)CCC2C3C1C4CCC(C4(CC3C)C)O
InChI InChI=1S/C20H30O2/c1-11-8-13-9-14(21)4-5-15(13)18-12(2)10-20(3)16(19(11)18)6-7-17(20)22/h9,11-12,15-19,22H,4-8,10H2,1-3H3/t11-,12+,15+,16+,17+,18-,19+,20+/m1/s1 Key:KVIKZOGGZHCGFH-RJMNTABLSA-N

Dimethandrolone (DMA), also known by its developmental code name CDB-1321, is an experimental androgen/anabolic steroid (AAS) and progestogen medication which is under investigation for potential clinical use. ^{[1] [2] [3]}

Dimethandrolone is an AAS, and hence is an agonist of the androgen receptor, the biological target of androgens like testosterone. ^[1] It is also a progestin, or a synthetic progestogen, and hence is an agonist of the progesterone receptor, the biological target of progestogens like progesterone. ^[1] Due to its androgenic and progestogenic activity, dimethandrolone has antigonadotropic effects. ^[1] It has no estrogenic activity. ^{[1] [4]}

Dimethandrolone was first described in 1997. ^[5] It was developed by the Contraceptive Development Branch of the National Institute of Child Health and Human Development, an agency in the United States government. ^{[1] [6]}

An ester and prodrug of dimethandrolone, dimethandrolone undecanoate (DMAU) (CDB-4521), is under development for potential use as a birth control pill for men and in androgen replacement therapy for men. ^{[1] [2] [3] [7]}

Side effects

See also: Anabolic steroid § Adverse effects

Pharmacology

Pharmacodynamics

Dimethandrolone is an AAS, though it has also been described as a selective androgen receptor modulator (SARM). ^{[1] [2] [3]} As an AAS, it is a potent agonist of the androgen receptor (AR). ^{[1] [2]}

Unlike testosterone and various other AAS, dimethandrolone is not metabolized by 5α-reductase. ^[2] In addition, the 5α-reduced derivative of dimethandrolone, 5α-dihydrodimethandrolone (5α-DHDMA), possesses only 30 to 40% of the potency of dimethandrolone as an agonist of the AR, indicating that dimethandrolone does not require potentiation by 5α-reductase for its activity as an AAS and that even if it were a substrate for 5α-reductase, it would not be potentiated in androgenic tissues like the skin and prostate. ^[2] As such, dimethandrolone and ester prodrugs of it like DMAU are thought to have a reduced risk of androgenic side effects and conditions such as benign prostatic hyperplasia, prostate cancer, pattern scalp hair loss, and acne relative to testosterone and certain other AAS. ^[2]

Dimethandrolone is not a substrate for aromatase, and for this reason, is not converted into the corresponding aromatic A-ring derivative 7α,11β-dimethylestradiol, a potent estrogen. ^{[3] [4]} As such, dimethandrolone is not estrogenic. ^[4] This is in contrast to nandrolone, which, although its rate of aromatization into the estrogen estradiol is reduced relative to that of testosterone, is still converted to a significant extent. ^[4]

Similarly to nandrolone and other 19-nortestosterone derivatives, dimethandrolone is a potent progestogen in addition to AAS. ^[1] This property may serve to augment its antigonadotropic activity, which in turn may improve its effectiveness as an antispermatogenic agent and male contraceptive. ^[1] This is salient and potentially beneficial as male contraceptives based on androgens alone have failed to produce satisfactory azoospermia in around one-third of men. ^[1]

Dimethandrolone has shown minimal potential for hepatotoxicity in animal studies, which is in accordance with the fact that it is not a 17α-alkylated AAS. ^[6]

Chemistry

See also: List of androgens/anabolic steroids

Dimethandrolone, also known as 7α,11β-dimethyl-19-nortestosterone or as 7α,11β-dimethylestr-4-en-17β-ol-3-one, is a synthetic estrane steroid and a non-17α-alkylated derivative of nandrolone (19-nortestosterone). ^[1]

Esters

Aside from the C17β undecanoate ester of dimethandrolone, DMAU (CDB-4521), ^{[1] [2] [3]} a few other esters, such as dimethandrolone buciclate (CDB-4386A) and dimethandrolone dodecylcarbonate (CDB-4730), have also been developed. ^{[8] [9]}

Analogues

Other AAS that are closely related to dimethandrolone (besides nandrolone) include trestolone (also known as 7α-methyl-19-nortestosterone (MENT)) and 11β-methyl-19-nortestosterone (11β-MNT) and their respective C17β esters trestolone acetate and 11β-MNT dodecylcarbonate (11β-MNTDC). ^{[1] [2]}

History

A patent for dimethandrolone was filed in 1997 and was granted in 1999. ^[5] Subsequently, a patent for DMAU and dimethandrolone buciclate was filed in 2002 and was granted to the United States government in 2003. ^[8] Dimethandrolone was developed under the code name CDB-1321 by the Contraceptive Development Branch of the National Institute of Child Health and Human Development, one of the National Institutes of Health in the United States Department of Health and Human Services. ^{[1] [6]}

References

1. Attardi BJ, Hild SA, Reel JR (June 2006). "Dimethandrolone undecanoate: a new potent orally active androgen with progestational activity". Endocrinology. 147 (6): 3016–26. doi:10.1210/en.2005-1524. PMID   16497801. S2CID   45745191.
2. Attardi BJ, Hild SA, Koduri S, Pham T, Pessaint L, Engbring J, et al. (October 2010). "The potent synthetic androgens, dimethandrolone (7α,11β-dimethyl-19-nortestosterone) and 11β-methyl-19-nortestosterone, do not require 5α-reduction to exert their maximal androgenic effects". The Journal of Steroid Biochemistry and Molecular Biology. 122 (4): 212–8. doi:10.1016/j.jsbmb.2010.06.009. PMC   2949447 . PMID   20599615.
3. Wang C, Swerdloff RS (November 2010). "Hormonal approaches to male contraception". Current Opinion in Urology. 20 (6): 520–4. doi:10.1097/MOU.0b013e32833f1b4a. PMC   3078035 . PMID   20808223.
4. Attardi BJ, Pham TC, Radler LC, Burgenson J, Hild SA, Reel JR (June 2008). "Dimethandrolone (7alpha,11beta-dimethyl-19-nortestosterone) and 11beta-methyl-19-nortestosterone are not converted to aromatic A-ring products in the presence of recombinant human aromatase". The Journal of Steroid Biochemistry and Molecular Biology. 110 (3–5): 214–22. doi:10.1016/j.jsbmb.2007.11.009. PMC   2575079 . PMID   18555683.
5. US 5952319,Cook CE, Kepler JA, Lee YW, Wani MW,"Androgenic steroid compounds and a method of making and using the same",published 1999, assigned to Research Triangle Institute 
6. Attardi BJ, Engbring JA, Gropp D, Hild SA (September–October 2011). "Development of dimethandrolone 17beta-undecanoate (DMAU) as an oral male hormonal contraceptive: induction of infertility and recovery of fertility in adult male rabbits". Journal of Andrology. 32 (5): 530–40. doi: 10.2164/jandrol.110.011817 . PMID   21164142.
7. "Dimethandrolone undecanoate shows promise as a male birth control pill". Press Release. Endocrine Society. March 18, 2018.
8. US 20030069215,Blye R, Kim H,"Methods of making and using 7a, 11b-dimethyl-17b-hydroxy-4-estren-3-one 17b-trans-4-n-butylcyclohexane carboxylate and 7a, 11b-dimethyl-17b-hydroxyestr-4-en-3-one 17-undecanoate.", assigned to US Government 
9. US 7820642,Blye R, Kim H,"Nandrolone 17β-carbonates",published 26 October 2010, assigned to US Government