dimethyltrienolone
{{Short description|Anabolic–androgenic steroid}}
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| IUPAC_name = (7R,8S,13S,14S,17S)-17-hydroxy-7,13,17-trimethyl-1,2,6,7,8,14,15,16-octahydrocyclopenta[a]phenanthren-3-one
| image = Dimethyltrienolone.svg
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| routes_of_administration = By mouth
| class = Androgen; Anabolic steroid; Progestogen
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| CAS_number_Ref = {{cascite|correct|CAS}}
| CAS_number = 10110-86-8
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| PubChem = 101678228
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| ChemSpiderID = 23208745
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 8GP0J5637H
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| ChEMBL = 128880
| synonyms = RU-2420; 7α,17α-Dimethyltrenbolone; 7α,17α-Dimethyl-δ9,11-19-nortestosterone; 7α,17α-Dimethylestra-4,9,11-trien-17β-ol-3-one
| C=20 | H=26 | O=2
| SMILES = C[C@@H]1CC2=CC(=O)CCC2=C3[C@@H]1[C@@H]4CC[C@]([C@]4(C=C3)C)(C)O
| StdInChI_Ref =
| StdInChI = 1S/C20H26O2/c1-12-10-13-11-14(21)4-5-15(13)16-6-8-19(2)17(18(12)16)7-9-20(19,3)22/h6,8,11-12,17-18,22H,4-5,7,9-10H2,1-3H3/t12-,17+,18-,19+,20+/m1/s1
| StdInChIKey_Ref =
| StdInChIKey = MEMDJKLEPFFNQS-ZGPIAVDESA-N
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Dimethyltrienolone (developmental code name RU-2420) is a synthetic, orally active, and extremely potent anabolic–androgenic steroid (AAS) and 17α-alkylated 19-nortestosterone (nandrolone) derivative which was never marketed for medical use.{{cite book|author=William Llewellyn|title=Anabolics|url=https://books.google.com/books?id=afKLA-6wW0oC|year=2009|publisher=Molecular Nutrition Llc|isbn=978-0967930473|pages=212–214}} It has among the highest known affinity of any AAS for the androgen (and progesterone) receptors,{{cite journal | vauthors = Waszkowycz B, Clark DE, Frenkel D, Li J, Murray CW, Robson B, Westhead DR | title = PRO_LIGAND: an approach to de novo molecular design. 2. Design of novel molecules from molecular field analysis (MFA) models and pharmacophores | journal = Journal of Medicinal Chemistry | volume = 37 | issue = 23 | pages = 3994–4002 | date = November 1994 | pmid = 7966160 | doi = 10.1021/jm00049a019 }}{{cite journal | vauthors = Loughney DA, Schwender CF | title = A comparison of progestin and androgen receptor binding using the CoMFA technique | journal = Journal of Computer-Aided Molecular Design | volume = 6 | issue = 6 | pages = 569–581 | date = December 1992 | pmid = 1291626 | doi = 10.1007/bf00126215 | s2cid = 22004130 | bibcode = 1992JCAMD...6..569L }} and has been said to be perhaps the most potent AAS to have ever been developed.
Pharmacology
=Pharmacodynamics=
Dimethyltrienolone is an extremely potent agonist of the androgen and progesterone receptors and hence AAS and progestogen. In animal bioassays, it was shown to possess more than 100 times the anabolic and androgenic potency of the reference AAS methyltestosterone. The drug is not a substrate for 5α-reductase and so is not potentiated or inactivated in so-called "androgenic" tissues like the prostate gland or skin. It is also not a substrate for aromatase and so has no estrogenic activity. Due to its lack of estrogenicity, dimethyltrienolone has no propensity for causing estrogenic side effects like gynecomastia. Because of its C17α methyl group and very high resistance to hepatic metabolism, dimethyltrienolone is said to be exceedingly hepatotoxic.
| class="wikitable center sortable mw-collapsible mw-collapsed" style="width:600px; text-align:left; margin-left:auto; margin-right:auto; border:none;"
|+ class="nowrap" | Relative affinities (%) of dimethyltrienolone and related steroids{{cite journal | vauthors = Delettré J, Mornon JP, Lepicard G, Ojasoo T, Raynaud JP | title = Steroid flexibility and receptor specificity | journal = Journal of Steroid Biochemistry | volume = 13 | issue = 1 | pages = 45–59 | date = January 1980 | pmid = 7382482 | doi = 10.1016/0022-4731(80)90112-0 }}{{cite journal | vauthors = Ojasoo T, Delettré J, Mornon JP, Turpin-VanDycke C, Raynaud JP | title = Towards the mapping of the progesterone and androgen receptors | journal = Journal of Steroid Biochemistry | volume = 27 | issue = 1–3 | pages = 255–269 | date = 1987 | pmid = 3695484 | doi = 10.1016/0022-4731(87)90317-7 }} | ||||||
| Compound || Chemical name || {{abbrlink|PR|Progesterone receptor}} || {{abbrlink|AR|Androgen receptor}} || {{abbrlink|ER|Estrogen receptor}} || {{abbrlink|GR|Glucocorticoid receptor}} || {{abbrlink|MR|Mineralocorticoid receptor}} | ||||||
|---|---|---|---|---|---|---|
| Testosterone | T | 1.0 | 100 | <0.1 | 0.17 | 0.9 |
| Nandrolone | 19-NT | 20 | 154 | <0.1 | 0.5 | 1.6 |
| Trenbolone | ∆9,11-19-NT | 74 | 197 | <0.1 | 2.9 | 1.33 |
| Trestolone | 7α-Me-19-NT | 50–75 | 100–125 | ? | <1 | ? |
| Normethandrone | 17α-Me-19-NT | 100 | 146 | <0.1 | 1.5 | 0.6 |
| Metribolone | ∆9,11-17α-Me-19-NT | 208 | 204 | <0.1 | 26 | 18 |
| Mibolerone | 7α,17α-DiMe-19-NT | 214 | 108 | <0.1 | 1.4 | 2.1 |
| Dimethyltrienolone | ∆9,11-7α,17α-DiMe-19-NT | 306 | 180 | 0.1 | 22 | 52 |
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| colspan="9" style="width: 1px;" | Values are percentages (%). Reference ligands (100%) were progesterone for the {{abbrlink|PR|progesterone receptor}}, testosterone for the {{abbrlink|AR|androgen receptor}}, estradiol for the {{abbrlink|ER|estrogen receptor}}, {{abbrlink|DEXA|dexamethasone}} for the {{abbrlink|GR|glucocorticoid receptor}}, and aldosterone for the {{abbrlink|MR|mineralocorticoid receptor}}. |
Chemistry
{{See also|List of androgens/anabolic steroids}}
Dimethyltrienolone, also known as 7α,17α-dimethyl-δ9,11-19-nortestosterone or as 7α,17α-dimethylestra-4,9,11-trien-17β-ol-3-one, as well as 7α,17α-dimethyltrenbolone, is a synthetic estrane steroid and a 17α-alkylated derivative of nandrolone (19-nortestosterone). It is the 7α,17α-dimethyl derivative of trenbolone and the 7α-methyl derivative of metribolone,{{cite book| vauthors = Rabe T, Kesel L, Runnebaum B | chapter = Antiprogestins| veditors = Ganten D, Pfaff D |title=Actions of Progesterone on the Brain| chapter-url = https://books.google.com/books?id=CFEICQAAQBAJ&pg=PA17 |date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-3-642-69728-9|pages=17–}} as well as the δ9,11 analogue of metribolone and the δ9,11, 17α-methylated derivative of trestolone.
History
Dimethyltrienolone was first described in 1967.{{cite book | vauthors = Mathieu J | title = Proceedings of the International Symposium on Drug Research, Montreal, Canada, June 12-14, 1967 | year = 1967 | page = 134 | publisher = Chemical Institute of Canada, Medical Chemistry Group, Montreal, Canada | url = https://books.google.com/books?id=A69ZnQAACAAJ}} It was never marketed for medical use.
See also
References
{{Reflist}}
{{Androgen receptor modulators}}
{{Progesterone receptor modulators}}
Category:1-Methylcyclopentanols