Synthesis and pharmacological evaluation of 4-halo progesterone derivatives as antiandrogen.
The pharmacological activity of eight pregnane derivatives 17-alpha acetoxyprogesterone 9, 17-alpha acetoxy-4, 5-epoxypregnan-3, 20-dione 10, 17-alpha acetoxy-4-chloro-4-pregnene-3, 20-dione 11, 17-alpha acetoxy-4-bromo-4-pregnene-3, 20-dione 12, 17-alpha hydroxy-4-bromo-4-pregnene-3, 20-dione 13, 4-chloro-17-alpha hydroxy-4-pregnene-3, 20-dione 14, 17-alpha benzoyloxy-4-bromo-4-pregnene-3, 20-dione 15 and 17-alpha benzoyloxy-4-chloro-4-pregnene-3, 20-dione 16 was determined. These compounds were evaluated as antiandrogens on gonadectomized hamster seminal vesicles. The pharmacological data in this study indicate that compounds 15 and 16 having a C-17 benzoyloxy moiety showed the highest antiandrogenic activity as measured by the reduction of the weight of the seminal vesicles, followed by the steroids 11 and 12 (17-alpha acetoxy group). The free alcohols 13 and 14 exhibited a lower antiandrogenic activity. Apparently, the ester moiety at C-17 is a necessary requirement for the presence of high antiandrogenic activity. Shows the inhibitory effect on the conversion of testosterone (T) to DHT, of the above described steroids as measured by the amount of produced DHT 2 expressed as pmoles of DHT/g of protein/h. Steroids 11, 12 and 16 showed a much higher inhibitory activity on the conversion of testosterone (T) to dihydrotestosterone (DHT) than presently used finasteride 3.
Cabeza
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Department of Biological Systems, Metropolitan University of Mexico, Mexico, D.F. Mexico.
Quiroz
A
A
Bratoeff
E
E
Murillo
M E
ME
Ramírez
E
E
Flores
G
G
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000378:metabolism; D000726:Androgen Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002855:Chromatography, Thin Layer; D006224:Cricetinae; D013196:Dihydrotestosterone / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008647:Mesocricetus; D009919:Orchiectomy; D009929:Organ Size / Q000187:drug effects; D011278:Pregnanes / Q000138:chemical synthesis* / Q000494:pharmacology; D014176:Protein Biosynthesis; D051381:Rats; D012669:Seminal Vesicles / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D013739:Testosterone / Q000378:metabolism
D000726:Androgen Antagonists; D011278:Pregnanes; D013196:Dihydrotestosterone; D013739:Testosterone; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase