17α-Allyl-19-nortestosterone: Difference between revisions
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{{Short description|Chemical compound}} |
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| IUPAC_name = (8''R'',9''S'',10''R'',13''S'',14''S'',17''R'')-17-hydroxy-13-methyl-17-prop-2-enyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[''a'']phenanthren-3-one |
| IUPAC_name = (8''R'',9''S'',10''R'',13''S'',14''S'',17''R'')-17-hydroxy-13-methyl-17-prop-2-enyl-1,2,6,7,8,9,10,11,12,14,15,16-dodecahydrocyclopenta[''a'']phenanthren-3-one |
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| image = 17α-Allyl-19-nortestosterone.svg |
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| CAS_number = 7358-46-5 |
| CAS_number = 7358-46-5 |
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| ChemSpiderID = 22270 |
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| UNII = EH9MJ5WS79 |
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| C=21 | H=30 | O=2 |
| C=21 | H=30 | O=2 |
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| molecular_weight = 314.469 g/mol |
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| SMILES = C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(CC=C)O)CCC4=CC(=O)CC[C@H]34 |
| SMILES = C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@]2(CC=C)O)CCC4=CC(=O)CC[C@H]34 |
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'''17α-Allyl-19-nortestosterone''', also known as '''3-ketoallylestrenol''' or as '''17α-allylestr-4-en-17β-ol-3-one''', is a [[progestin]] which was never marketed.<ref name="ColtonNysted1957">{{cite journal| |
'''17α-Allyl-19-nortestosterone''', also known as '''3-ketoallylestrenol''' or as '''17α-allylestr-4-en-17β-ol-3-one''', is a [[progestin]] which was never marketed.<ref name="ColtonNysted1957">{{cite journal| vauthors = Colton FB, Nysted LN, Riegel B, Raymond AL |title=17-Alkyl-19-nortestosterones|journal=Journal of the American Chemical Society|volume=79|issue=5|year=1957|pages=1123–1127|issn=0002-7863|doi=10.1021/ja01562a028}}</ref><ref name="pmid13609555">{{cite journal | vauthors = Miyake T, Pincus G | title = Progestational activity of certain 19-norsteroids and progesterone derivatives | journal = Endocrinology | volume = 63 | issue = 6 | pages = 816–824 | date = December 1958 | pmid = 13609555 | doi = 10.1210/endo-63-6-816 }}</ref><ref name="Dorfman2016">{{cite book| vauthors = Miyake T | chapter = Progestational Substances | veditors = Dorfman RI |title=Methods in Hormone Research | volume = 2 Bioassay | chapter-url = https://books.google.com/books?id=WS_LBAAAQBAJ&pg=PA134|date=3 February 2016|publisher=Elsevier|isbn=978-1-4832-7276-4|pages=134–}}</ref><ref name="pmid18395441">{{cite journal | vauthors = McRobb L, Handelsman DJ, Kazlauskas R, Wilkinson S, McLeod MD, Heather AK | title = Structure-activity relationships of synthetic progestins in a yeast-based in vitro androgen bioassay | journal = The Journal of Steroid Biochemistry and Molecular Biology | volume = 110 | issue = 1–2 | pages = 39–47 | date = May 2008 | pmid = 18395441 | doi = 10.1016/j.jsbmb.2007.10.008 | s2cid = 5612000 }}</ref> It is a combined [[chemical derivative|derivative]] of the [[anabolic–androgenic steroid]] and [[progestogen]] [[nandrolone]] (19-nortestosterone) and the [[antiandrogen]] [[allyltestosterone]] (17α-allyltestosterone).<ref name="ColtonNysted1957" /><ref name="pmid13609555" /><ref name="Dorfman2016" /> The drug is a major [[active metabolite]] of [[allylestrenol]], which is thought to be a [[prodrug]] of 17α-allyl-19-nortestosterone.<ref name="pmid18395441" /><ref name="Zeelen1990">{{cite book| vauthors = Zeelen FJ |title=Medicinal chemistry of steroids|url=https://books.google.com/books?id=px9tAAAAMAAJ|year=1990|publisher=Elsevier Science Limited|isbn=978-0-444-88727-6|pages=108–109|quote=Other examples are allylestrenol (42), a pro-drug converted to the 3-keto analogue (43), which is used in the treatment of threatened abortion [78,79] and altrenogest (44), used in sows and mares to suppress ovulation and estrus behaviour [80]. [...] Progestins with a 17a-allyl side chain: (42) allylestrenol, (43), (44) altrenogest.}}</ref> |
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17α-Allyl-19-nortestosterone has 24% of the [[affinity (pharmacology)|affinity]] of [[ORG-2058]] and 186% of the affinity of [[progesterone (medication)|progesterone]] for the [[progesterone receptor]], 4.5% of the affinity of [[testosterone (medication)|testosterone]] for the [[androgen receptor]], 9.8% of the affinity of [[dexamethasone]] for the [[glucocorticoid receptor]], 2.8% of the affinity of testosterone for [[sex hormone-binding globulin]], and less than 0.2% of the affinity of [[estradiol (medication)|estradiol]] for the [[estrogen receptor]].<ref name="BerginkLoonen1985">{{cite journal | vauthors = Bergink EW, Loonen PB, Kloosterboer HJ | title = Receptor binding of allylestrenol, a progestagen of the 19-nortestosterone series without androgenic properties | journal = Journal of Steroid Biochemistry | volume = 23 | issue = 2 | pages = 165–168 | date = August 1985 | pmid = 3928974 | doi = 10.1016/0022-4731(85)90232-8 }}</ref><ref name="Madjerekde Visser1960">{{cite journal | vauthors = Madjerek Z, De Visser J, Van Der Vies J, Overbeek GA | title = Allylestrenol, a pregnancy maintaining oral gestagen | journal = Acta Endocrinologica | volume = 35 | issue = I | pages = 8–19 | date = September 1960 | pmid = 13765069 | doi = 10.1530/acta.0.XXXV0008 }}</ref> The affinity of 17α-allyl-19-nortestosterone for the androgen receptor was less than that of [[norethisterone]] and [[medroxyprogesterone acetate]] and its affinity for sex hormone-binding globulin was much lower than that of norethisterone.<ref name="BerginkLoonen1985" /> These findings may help to explain the absence of [[teratogen]]ic effects of allylestrenol on the [[external genitalia]] of female and male rat [[fetus]]es.<ref name="BerginkLoonen1985" /> |
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{| class="wikitable center mw-collapsible mw-collapsed" style="width:450px; text-align:left; margin-left:auto; margin-right:auto; border:none;" |
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|+ class="nowrap" | Relative affinities (%) of allylestrenol and metabolites<ref name="BerginkLoonen1985" /> |
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! Compound || {{abbrlink|PR|Progesterone receptor}} || {{abbrlink|AR|Androgen receptor}} || {{abbrlink|ER|Estrogen receptor}} || {{abbrlink|GR|Glucocorticoid receptor}} || {{abbrlink|MR|Mineralocorticoid receptor}} || {{abbrlink|SHBG|Sex hormone-binding globulin}} || {{abbrlink|CBG|Corticosteroid binding globulin}} |
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|- |
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| [[Allylestrenol]] || 0 || 0 || 0 || 0 || ? || 1 || ? |
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|- |
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| {{abbr|17α-Allyl-19-NT|17α-Allyl-19-nortestosterone}} || 186 || 5 || 0 || 10 || ? || 3 || ? |
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|- class="sortbottom" |
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| colspan="9" style="width: 1px;" | Values are percentages (%). Reference [[ligand (biochemistry)|ligand]]s (100%) were {{abbrlink|P4|progesterone (medication)}} for the {{abbrlink|PR|progesterone receptor}}, {{abbrlink|T|testosterone (medication)}} for the {{abbrlink|AR|androgen receptor}}, [[estradiol (medication)|{{abbr|E2|estradiol}}]] for the {{abbrlink|ER|estrogen receptor}}, {{abbrlink|DEXA|dexamethasone}} for the {{abbrlink|GR|glucocorticoid receptor}}, [[aldosterone]] for the {{abbrlink|MR|mineralocorticoid receptor}}, {{abbrlink|T|testosterone (medication)}} for {{abbrlink|SHBG|sex hormone-binding globulin}}, and [[hydrocortisone|cortisol]] for {{abbrlink|CBG|Corticosteroid-binding globulin}}. |
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== See also == |
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* [[Altrenogest]] |
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* [[Ethinyltestosterone]] |
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* [[Vinyltestosterone]] |
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{{Progesterone receptor modulators}} |
{{Progesterone receptor modulators}} |
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{{DEFAULTSORT:Allyl-19-nortestosterone, 17α-}} |
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[[Category:Abandoned drugs]] |
[[Category:Abandoned drugs]] |
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[[Category: |
[[Category:Tertiary alcohols]] |
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[[Category:Allyl compounds]] |
[[Category:Allyl compounds]] |
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[[Category:Estranes]] |
[[Category:Estranes]] |
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[[Category:Human drug metabolites]] |
[[Category:Human drug metabolites]] |
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[[Category: |
[[Category:Enones]] |
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[[Category:Progestogens]] |
[[Category:Progestogens]] |
Latest revision as of 08:37, 12 August 2023
Clinical data | |
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Other names | Allylnortestosterone; Allylestrenolone; Allylnandrolone; 3-Ketoallylestrenol; 17α-Allylestr-4-en-17β-ol-3-one; Allylestrenolone |
Drug class | Progestogen |
Identifiers | |
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CAS Number | |
PubChem CID | |
ChemSpider | |
UNII | |
Chemical and physical data | |
Formula | C21H30O2 |
Molar mass | 314.469 g·mol−1 |
3D model (JSmol) | |
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17α-Allyl-19-nortestosterone, also known as 3-ketoallylestrenol or as 17α-allylestr-4-en-17β-ol-3-one, is a progestin which was never marketed.[1][2][3][4] It is a combined derivative of the anabolic–androgenic steroid and progestogen nandrolone (19-nortestosterone) and the antiandrogen allyltestosterone (17α-allyltestosterone).[1][2][3] The drug is a major active metabolite of allylestrenol, which is thought to be a prodrug of 17α-allyl-19-nortestosterone.[4][5]
17α-Allyl-19-nortestosterone has 24% of the affinity of ORG-2058 and 186% of the affinity of progesterone for the progesterone receptor, 4.5% of the affinity of testosterone for the androgen receptor, 9.8% of the affinity of dexamethasone for the glucocorticoid receptor, 2.8% of the affinity of testosterone for sex hormone-binding globulin, and less than 0.2% of the affinity of estradiol for the estrogen receptor.[6][7] The affinity of 17α-allyl-19-nortestosterone for the androgen receptor was less than that of norethisterone and medroxyprogesterone acetate and its affinity for sex hormone-binding globulin was much lower than that of norethisterone.[6] These findings may help to explain the absence of teratogenic effects of allylestrenol on the external genitalia of female and male rat fetuses.[6]
Compound | PR | AR | ER | GR | MR | SHBG | CBG | |
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Allylestrenol | 0 | 0 | 0 | 0 | ? | 1 | ? | |
17α-Allyl-19-NT | 186 | 5 | 0 | 10 | ? | 3 | ? | |
Values are percentages (%). Reference ligands (100%) were P4 for the PR , T for the AR , E2 for the ER , DEXA for the GR , aldosterone for the MR , T for SHBG , and cortisol for CBG . |
See also
[edit]References
[edit]- ^ a b Colton FB, Nysted LN, Riegel B, Raymond AL (1957). "17-Alkyl-19-nortestosterones". Journal of the American Chemical Society. 79 (5): 1123–1127. doi:10.1021/ja01562a028. ISSN 0002-7863.
- ^ a b Miyake T, Pincus G (December 1958). "Progestational activity of certain 19-norsteroids and progesterone derivatives". Endocrinology. 63 (6): 816–824. doi:10.1210/endo-63-6-816. PMID 13609555.
- ^ a b Miyake T (3 February 2016). "Progestational Substances". In Dorfman RI (ed.). Methods in Hormone Research. Vol. 2 Bioassay. Elsevier. pp. 134–. ISBN 978-1-4832-7276-4.
- ^ a b McRobb L, Handelsman DJ, Kazlauskas R, Wilkinson S, McLeod MD, Heather AK (May 2008). "Structure-activity relationships of synthetic progestins in a yeast-based in vitro androgen bioassay". The Journal of Steroid Biochemistry and Molecular Biology. 110 (1–2): 39–47. doi:10.1016/j.jsbmb.2007.10.008. PMID 18395441. S2CID 5612000.
- ^ Zeelen FJ (1990). Medicinal chemistry of steroids. Elsevier Science Limited. pp. 108–109. ISBN 978-0-444-88727-6.
Other examples are allylestrenol (42), a pro-drug converted to the 3-keto analogue (43), which is used in the treatment of threatened abortion [78,79] and altrenogest (44), used in sows and mares to suppress ovulation and estrus behaviour [80]. [...] Progestins with a 17a-allyl side chain: (42) allylestrenol, (43), (44) altrenogest.
- ^ a b c d Bergink EW, Loonen PB, Kloosterboer HJ (August 1985). "Receptor binding of allylestrenol, a progestagen of the 19-nortestosterone series without androgenic properties". Journal of Steroid Biochemistry. 23 (2): 165–168. doi:10.1016/0022-4731(85)90232-8. PMID 3928974.
- ^ Madjerek Z, De Visser J, Van Der Vies J, Overbeek GA (September 1960). "Allylestrenol, a pregnancy maintaining oral gestagen". Acta Endocrinologica. 35 (I): 8–19. doi:10.1530/acta.0.XXXV0008. PMID 13765069.