17a-Methyl-19-nortestosterone

Testosterone (5.45) is the prototypic androgen sex hormone. Testosterone is synthesized by the testes, and must be reduced to dihydrotestosterone (5.46, DHT) before it will bind to the receptor. Among highly active synthetic testosterone analogs, 7a-methyl-19-nortestosterone (5.47) and oxandrolone (5.48) have about 100 times greater activity than testosterone as androgens. 17a-Methyltestosterone (5.49) is orally active. 

Methyl 3a,6a-dihydroxycholanate, 240 1-Methylestrone 3-methyl ether, 10, 27 4b/3-Methyl-7-ethylenedioxy-1,2,3,4, 4a ,4b/3,5,6,7,8,10,1 Oaa-dodecahydro-phenanthrene-1 /3,4/3-diol, 236 14C-Methyl iodide, 211 ds-Methyl iodide, 210, 214 Methyl lithocholate tosylate, 329 1-Methyl-19-nortestosterone, 27 6a-Methylprednisolone, 410 6a-Methylprednisolone BMD, 410 16/3-Methylprednisone, 87 18-Methylpregn-4-ene-3/3,17a,20f-triol, 243 20-Methylpregn-5-en-3/3-ol, 415 17a-Methylpregnenolone acetate, 48 17a-Methyltestosterone, 438 16/3-Methyl- 11a,17a,21 -trihydroxy- 5 /3-pregnane-3,20-dione 21-acetate, 299, 300 20-Methyl-3/3-trityloxypregn-5-ene, 415 3/3-Methoxycholestane, 136 1-Methoxycyclohexene, 18 3-Methoxyestra-3,5(10)-diene, 18, 27... 

N-methylmorpholine oxide-hydrogen peroxide, 184, 221, 223 4-Methyl-19-nortestosterone, 89 16/3-Methyl-l 6a, 17a-oxidopregn-4-ene-... 

CAP in high doses (40-60 mg/day, p.o.) and 17a-methyl-B-nortestosterone applied topically significantly decreased sebum production.The paired costovertebral organs of the hamster is used in an assay to distinguish direct topical activity from activity due to systanic effect. In this assay topically applied CAP, 19-nor-CAP, and A -chlormadinone-16,17a-acetonide were completely inactive. Further, A -CAP and 46 showed activity but it is questionable whether it was a direct "end" organ effect. It appears that topical treatment of acne with steroidal anti-androgens is still far from realization. 

A once-a-month oral contraceptive may be well suited for underdeveloped countries where medical supervision is limited. Norgestrel (17a-ethynyl-18-methyl-19-nortestosterone), in combination with ethynyl estradiol showed good contraceptive efficacy given 21 days in a cycle. The lower dally doses of... 

Nortestosterone. The I lj8-hydroxy 17a-methyl (N-66) derivative compared to 17a-methylnortestosterone (N-4) and the 1 lj8-hydroxy 17a-ethyl (N-67) derivative compared to 17a-ethylnortestosterone (N-5) show increased androgenic and anabolic activities and, in the first case, a favorable anabolic-androgenic ratio. 

In the 19-nortestosterone series introduction of a hydroxyl group leads to a substantial increase in the androgenic and anabolic potencies in two cases. 17a-Methyl-l l/8,17j8-dihydroxy-19-norandrost-4-en-3-one (N-66) and 17a-methyl-4,17/8-dihydroxy-19-norandrost-4-en-3-one (N-74) both display favorable anabolic-androgenic ratios. The increased activity of the 4-hydroxy derivative N-74 is particularly interesting, since 4-hydroxy substitution usually decreases the androgenic activity (see N-77). 

Others. The 19-nortestosterone analogs, which instead of the d -3-ketone system contain the A -3-ketone system (unconjugated ketone) showed very similar androgenic and anabolic potencies compared to the A -3-ketone compounds [68]. It is most likely that the A -3-ketone compounds, 17a-ethynyl-17)3-hydroxy-19-norandrost-5-en-3-one (N-37), 17o -ethyl-17 -hydroxy-19-norandrost-5-en-3-one (N-38), and Ha-methyl-17/3-hydroxy-19-norandrost-5-en-3-one (N-39) under the influence of the acid pH of the stomach are rearranged to the A -3-ketones. 

In addition to the above-described compounds, there are a few other 19-nortestosterone derivatives which display a favorable anabolic-androgenic ratio by having lower androgenic activities and maintaining the anabolic activity of the standard compound 17a-methyl-l 7j8-hydroxy-19-norandrost-2-ene (N-29), 2-cyano-17/3-acetoxy-19-norandrost-2-ene acetoxy-19-norandrost-4-eno[2,3-c ]isoxazole (N-70), 17a-methyl-17/3-hydroxy-19-norandrost-4-eno[2,3-fii]isoxazole (N-76), and I7a-methyl-17/3-hydroxy-5a-estran-3-one (N-90). 

For drug therapy, native hormones have been replaced to a large extent by synthetic or semisynthetic derivatives that possess higher and more selective therapeutic potential. Some very important synthetic androgen analogs are the esters and the 17-methyl derivative of testosterone. Of the numerous related anabolic steroids, the esters of nandrolone (19-nortestosterone), methandienone (17a-methyl-17-hydroxy-l,4-androstadien-3-one), stanozolol (17a-methyl-2 H-5a-androst-2-eno[3,2-c]pyrazol-17-ol, and trenbolone acetate (17)S-hydroxy-4,9,ll-estratrien-3-one acetate) are most frequently used. 

---