Chemistry:17α-Alkylated anabolic steroid

Short description: Class of chemical compounds

A 17α-alkylated anabolic steroid is a synthetic anabolic–androgenic steroid (AAS) that features an alkyl group, specifically a methyl or ethyl group, at the C17α position. Unlike many other AAS, 17α-alkylated AAS are orally active and do not require intramuscular injection. However, they uniquely possess a high potential for hepatotoxicity, which simultaneously limits their use. In addition, some have a high risk of gynecomastia due to uniquely high estrogenic activity, although this does not apply to 17α-alkylated AAS that are also 4,5α-reduced or 19-demethylated (i.e., that are also dihydrotestosterone (DHT) or nandrolone derivatives, respectively). The prototypical example of a 17α-alkylated AAS is methyltestosterone (17α-methyltestosterone).

Structure-activity relationships

Extension of the C17α alkyl chain longer than an ethyl group abolishes androgenic activity and converts the drug into an antiandrogen, as in topterone (17α-propyltestosterone) and allylestrenol (17α-allyl-3-deketo-19-nortestosterone) (an extended-chain variant of ethylestrenol). Conversely, replacement of the C17α alkyl group with an ethynyl group greatly reduces but does not abolish androgenic activity, as in ethisterone (17α-ethynyltestosterone) and norethisterone (17α-ethynyl-19-nortestosterone). Similarly to extension of the C17α alkyl chain, extension of the C17α ethynyl chain abolishes androgenic activity, as with dimethisterone (6α,21-dimethylethisterone). Dienogest, which is antiandrogenic, features extension of the C17α chain in the form of a cyanomethyl group at the C17α position.

List of 17α-alkylated AAS

Testosterone derivatives

• Marketed
  • Bolasterone
  • Calusterone
  • Chlorodehydromethyltestosterone (CDMT)
  • Fluoxymesterone
  • Formebolone
  • Metandienone (methandrostenolone)
  • Methandriol (methylandrostenediol)
  • Methyltestosterone
  • Oxymesterone
  • Penmesterol (penmestrol)
  • Tiomesterone
• Never marketed
  • Chlorodehydromethylandrostenediol (CDMA)
  • Chloromethylandrostenediol (CMA)
  • Enestebol
  • Ethyltestosterone
  • Hydroxystenozole
  • Methylclostebol (chloromethyltestosterone)

Dihydrotestosterone derivatives

• Marketed
  • Androisoxazole
  • Furazabol
  • Mebolazine (dimethazine, dymethazine)
  • Mestanolone (methylandrostanolone)
  • Oxandrolone
  • Oxymetholone
  • Stanozolol
• Never marketed
  • Desoxymethyltestosterone (DMT)
  • Methasterone (methyldrostanolone)
  • Methyl-1-testosterone (methyl-δ¹-DHT)
  • Methylepitiostanol
  • Methylstenbolone

Nandrolone (19-nortestosterone) derivatives

• Marketed
  • Ethylestrenol (ethylnandrol)
  • Mibolerone
  • Norethandrolone (ethylnandrolone, ethylestrenolone)
  • Normethandrone (methylestrenolone, normethisterone)
  • Propetandrol (propethandrol)
• Never marketed
  • Bolenol (ethylnorandrostenol)
  • Dimethyltrienolone
  • Ethyldienolone
  • Methyldienolone
  • Methylhydroxynandrolone
  • Metribolone (methyltrienolone)
  • Norboletone (norbolethone)
  • Tetrahydrogestrinone (THG)

See also

• List of androgens/anabolic steroids

References

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| name = Androgens and antiandrogens
| title = Androgens and antiandrogens
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| group1 = Androgens
(incl. AAS)

| list1 =

AR agonists

Testosterone derivatives: Androstenediol dipropionate Boldenone undecylenate Clostebol Clostebol acetate Clostebol caproate Clostebol propionate Cloxotestosterone acetate Prasterone (dehydroepiandrosterone, DHEA) Prasterone enanthate (DHEA enanthate) Prasterone sulfate (DHEA sulfate) Quinbolone Testosterone# Testosterone esters (e.g., testosterone cypionate, testosterone enanthate]], testosterone propionate]], testosterone undecanoate]], testosterone ester mixture]]s (Deposterona, Omnadren, Sustanon, Testoviron Depot)) Dihydrotestosterone derivatives: Androstanolone (stanolone, dihydrotestosterone, DHT) Androstanolone esters Bolazine capronate Drostanolone propionate (dromostanolone propionate) Epitiostanol Mepitiostane Mesterolone Metenolone acetate (methenolone acetate) Metenolone enanthate (methenolone enanthate) Stenbolone acetate 19-Nortestosterone derivatives: Bolandiol dipropionate Nandrolone esters (e.g., nandrolone decanoate, nandrolone phenylpropionate) Norclostebol Norclostebol acetate Oxabolone cipionate (oxabolone cypionate) Trenbolone acetate Trenbolone hexahydrobenzylcarbonate (trenbolone cyclohexylmethylcarbonate) 17α-Alkylated testosterone derivatives: Bolasterone Calusterone Chlorodehydromethyltestosterone (CDMT) Fluoxymesterone Formebolone Metandienone (methandienone, methandrostenolone) Methandriol (methylandrostenediol) Methandriol bisenanthoyl acetate Methandriol dipropionate Methandriol propionate Methyltestosterone Methyltestosterone 3-hexyl ether Oxymesterone Penmesterol Tiomesterone (thiomesterone) 17α-Alkylated dihydrotestosterone derivatives: Androisoxazole Furazabol Mebolazine (dimethazine) Mestanolone Oxandrolone Oxymetholone Stanozolol 17α-Alkylated 19-nortestosterone derivatives: Ethylestrenol Mibolerone Norethandrolone Normethandrone (methylestrenolone, normethisterone) Propetandrol (propethandrol) 17α-Vinyltestosterone derivatives: Norvinisterone (vinylnortestosterone) 17α-Ethynyltestosterone derivatives: Danazol Gestrinone Progestins (e.g., ethisterone (ethynyltestosterone), levonorgestrel, norgestrel, norethisterone (norethindrone), [[Chemistry:Lynestrlynestrenol, Norgestrienone|norgestrienone]]) Tibolone Progesterone derivatives: Medroxyprogesterone acetate

Progonadotropins

Antiestrogens (e.g., tamoxifen, Chemistry:Clomifene

| group2 = Antiandrogens
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  | group1 = AR antagonists
  | list1 =

• Steroidal: Abiraterone acetate
• Canrenone
• Chlormadinone acetate
• Cyproterone acetate
• Delmadinone acetate
• Dienogest
• Drospirenone
• Medrogestone
• Megestrol acetate
• Nomegestrol acetate
• Osaterone acetate
• Oxendolone
• Potassium canrenoate
• Spironolactone

• Nonsteroidal: Apalutamide
• Bicalutamide
• Cimetidine
• Darolutamide
• Enzalutamide
• Flutamide
• Ketoconazole
• Nilutamide
• Seviteronel^†
• Topilutamide (fluridil)

  | group2 = Steroidogenesis
inhibitors

| list2 =

5α-Reductase	Alfatradiol Dutasteride Epristeride Finasteride Saw palmetto extract
Others	Abiraterone acetate Aminoglutethimide Bifluranol Cyproterone acetate Flutamide Ketoconazole Nilutamide Seviteronel† Spironolactone

  | group3 = Antigonadotropins
  | list3 =

• D₂ receptor antagonists (prolactin releasers) (e.g., domperidone, metoclopramide, risperidone, haloperidol, chlorpromazine, sulpiride)
• Estrogens (e.g., bifluranol, [[diethylstilbestrol, estradiol, estradiol esters, ethinylestradiol, ethinylestradiol sulfonate, paroxypropione)
• GnRH agonists (e.g., leuprorelin)
• GnRH antagonists (e.g., cetrorelix)
• Progestogens (incl., chlormadinone acetate, [[cyproterone acetate, hydroxyprogesterone caproate, gestonorone caproate, [[Chemistry:Medroxyprogesterone medroxyprogesterone acetate, Chemistry:Megestrol acetate|megestrol acetate]])

  | group4 = Others
  | list4 =

• Androstenedione immunogens: Androvax (androstenedione albumin)
• Ovandrotone albumin (Fecundin)

}}

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| list3 =

• ^#WHO-EM
• ^‡Withdrawn from market
• Clinical trials:
  • ^†Phase III
  • ^§Never to phase III

See also

Androgen receptor modulators

Estrogens and antiestrogens

Progestogens and antiprogestogens

List of androgens/anabolic steroids

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