11β-Methyl-19-nortestosterone

11β-Methyl-19-nortestosterone
Clinical data
Other names	11β-MNT; 11β-Methylestr-4-en-17β-ol-3-one
Routes of; administration	By mouth
Drug class	Androgen; Anabolic steroid; Progestogen
Identifiers
	IUPAC name (8R,9S,10R,11S,13S,14S,17S)-17-hydroxy-11,13-dimethyl-2,6,7,8,9,10,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-one;
CAS Number	18046-77-0 ; 904901-01-5 (dodecylcarbonate);
PubChem CID	68648057;
ChemSpider	52085460;
UNII	7HK4M3941F;
Chemical and physical data
Formula	C19H28O2
Molar mass	288.431 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES C[C@H]1C[C@]2(C)[C@@H](O)CC[C@H]2[C@@H]3CCC4=CC(=O)CC[C@@H]4[C@@H]13;
	InChI InChI=1S/C19H28O2/c1-11-10-19(2)16(7-8-17(19)21)15-5-3-12-9-13(20)4-6-14(12)18(11)15/h9,11,14-18,21H,3-8,10H2,1-2H3/t11-,14-,15-,16-,17-,18+,19-/m0/s1; Key:QCNNHARIRLYUAB-CTPXPINYSA-N;

11β-Methyl-19-nortestosterone (11β-MNT) is a synthetic and orally active anabolic–androgenic steroid (AAS) and a derivative of nandrolone (19-nortestosterone) which was developed by the Contraceptive Development Branch (CDB) of the National Institute of Child Health and Human Development (NICHD) and has not been marketed at this time.[1][2][3]

The C17β dodecyl carbonate ester of 11β-MNT, 11β-methyl-19-nortestosterone 17β-dodecylcarbonate (11β-MNTDC) (CDB-4754), is a prodrug of 11β-MNT.[1][2][3] Along with the closely related AAS dimethandrolone (7α,11β-dimethyl-19-nortestosterone; CDB-1321) and its ester prodrug dimethandrolone undecanoate (CDB-4521), 11β-MNT and 11β-MNTDC are under investigation as potential male contraceptives and to treat male hypogonadism.[1][2][3]

Side effects

Pharmacology

Pharmacodynamics

11β-MNT does not undergo aromatization into the corresponding estrogenic metabolite 11β-methylestradiol, and for this reason, has no potential for estrogenic side effects such as gynecomastia.[2] In addition, unlike testosterone, 11β-MNT does not appear to undergo 5α-reduction into the corresponding 5α-dihydrogenated metabolite 5α-dihydro-11β-MNT (5α-DHMNT).[3] This conclusion is based on the fact that 5α-DHMNT is 4 to 8 times as potent as 11β-MNT in terms of androgenicity in animal bioassays, yet the co-administration of the 5α-reductase inhibitor dutasteride with 11β-MNT had no influence on its potency in assays using tissues that express 5α-reductase like the ventral prostate and seminal vesicles.[3] Due to lack of potentiation by 5α-reductase in androgenic tissues like the skin, hair follicles, and prostate gland, 11β-MNT may have a lower risk of certain side effects such as oily skin, acne, androgenic alopecia (pattern hair loss), prostate enlargement, and prostate cancer than testosterone and certain other AAS.[3]

Similarly to nandrolone, dimethandrolone, and other 19-nortestosterone derivatives, 11β-MNT has been found to possess progestogenic activity.[4] Because of its dual activity as an AAS and progestogen, 11β-MNT may have greater efficacy in suppression of spermatogenesis and hence male fertility than pure AAS like testosterone.[4]

Oral 11β-MNT has shown little to no potential for hepatotoxicity in animals, similarly to testosterone but unlike 17α-alkylated AAS like methyltestosterone.[5] The drug notably shows a much lower hepatotoxic potential than dimethandrolone and trestolone (7α-methyl-19-nortestosterone; MENT), which may have an increased risk due to their shared C7α methyl group (although a risk that is still significantly lower than that of 17α-alkylated AAS).[5]

Chemistry

11β-MNT, or 11β-methyl-19-nortestosterone, also known as 11β-methylestr-4-en-17β-ol-3-one, is a synthetic estrane steroid and a non-17α-alkylated derivative of nandrolone (19-nortestosterone).[4]

References

Attardi BJ, Marck BT, Matsumoto AM, Koduri S, Hild SA (2011). "Long-term effects of dimethandrolone 17β-undecanoate and 11β-methyl-19-nortestosterone 17β-dodecylcarbonate on body composition, bone mineral density, serum gonadotropins, and androgenic/anabolic activity in castrated male rats". J. Androl. 32 (2): 183–92. doi:10.2164/jandrol.110.010371. PMID 20798389.
Attardi BJ, Pham TC, Radler LC, Burgenson J, Hild SA, Reel JR (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". J. Steroid Biochem. Mol. Biol. 110 (3–5): 214–22. doi:10.1016/j.jsbmb.2007.11.009. PMC 2575079. PMID 18555683.
Attardi BJ, Hild SA, Koduri S, Pham T, Pessaint L, Engbring J, Till B, Gropp D, Semon A, Reel JR (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". J. Steroid Biochem. Mol. Biol. 122 (4): 212–8. doi:10.1016/j.jsbmb.2010.06.009. PMC 2949447. PMID 20599615.
Attardi BJ, Hild SA, Reel JR (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.
Hild SA, Attardi BJ, Koduri S, Till BA, Reel JR (2010). "Effects of synthetic androgens on liver function using the rabbit as a model". J. Androl. 31 (5): 472–81. doi:10.2164/jandrol.109.009365. PMC 2943539. PMID 20378929.

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[pmid20798389-1] Attardi BJ, Marck BT, Matsumoto AM, Koduri S, Hild SA (2011). "Long-term effects of dimethandrolone 17β-undecanoate and 11β-methyl-19-nortestosterone 17β-dodecylcarbonate on body composition, bone mineral density, serum gonadotropins, and androgenic/anabolic activity in castrated male rats". J. Androl. 32 (2): 183–92. doi:10.2164/jandrol.110.010371. PMID 20798389.

[pmid18555683-2] Attardi BJ, Pham TC, Radler LC, Burgenson J, Hild SA, Reel JR (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". J. Steroid Biochem. Mol. Biol. 110 (3–5): 214–22. doi:10.1016/j.jsbmb.2007.11.009. PMC 2575079. PMID 18555683.

[pmid20599615-3] Attardi BJ, Hild SA, Koduri S, Pham T, Pessaint L, Engbring J, Till B, Gropp D, Semon A, Reel JR (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". J. Steroid Biochem. Mol. Biol. 122 (4): 212–8. doi:10.1016/j.jsbmb.2010.06.009. PMC 2949447. PMID 20599615.

[pmid16497801-4] Attardi BJ, Hild SA, Reel JR (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.

[pmid20378929-5] Hild SA, Attardi BJ, Koduri S, Till BA, Reel JR (2010). "Effects of synthetic androgens on liver function using the rabbit as a model". J. Androl. 31 (5): 472–81. doi:10.2164/jandrol.109.009365. PMC 2943539. PMID 20378929.