| 摘要 |
1,156,130. B-Nor-steroids. SMITH KLINE & FRENCH LABORATORIES. 19 Sept., 1967 [21 Sept., 1966], No. 42706/67. Headings C2C and C2U. Novel compounds of formula or C(H)(α- or #-CH 3 ) and R<SP>1</SP> is hydrogen, methyl, or ethyl, and the 17-esters thereof, are prepared by adding a 1,2-methylene group (e.g. with dimethyl sulphoxonium methylide) across the 1,2-double bond of the corresponding B-nor-1,4-androstadien-3-one, which in turn is obtained by chemical or microbiological dehydrogenation of the corresponding B-norandrost-4-en-3-one, e.g. using Septomyxa affinis. The 17-esters of the invention are obtainable from the 17-ols by conventional acylation. 6,6 - Ethylene - 17# - hydroxy - 17α - methyl- # - nor - androst - 4 - en - 3 - one is prepared by the sequence: 17α - methylandrost - 5 - ene- 3#,17# - diol-#its 3,17-diacetate-#3#,17#- diacetoxy - 17α - methyl - 5,6 - seco - androstan- 5 - on - 6 - al-#the corresponding 6 - oic acid-#3#,17# - diacetoxy - 17α methyl - 5#- hydroxy - # - nor - androstan - 6 - carboxylic acid 5,6 - lactone-#6# - hydroxymethyl - 17α- methyl - B - nor - androstane, - 3#,5#,17# - trial -#5#,17# - dihydroxy - 6# - hydroxymethyl- 17α - methyl - B - nor - androstan - 3 - one-# 6 - methylene - 17# - hydroxy - 17α - methyl - B- nor - androst - 4 - en - 3 - one-#desired compound. The corresponding 17α-ethyl compound is prepared analogously. 6,6 - Ethylene - 17# - hydroxy - B - nor - androst - 4 - en - 3 - one is prepared by the sequence: 3# - acetoxy - 5# - hydroxy - 17 - oxo- B - nor - androstan - 6 - carboxylic acid 5,6- lactone-#6# - hydroxymethyl - B - nor - androstane - 3#,5#,17# - triol-#6# - hydroxymethyl- 5# - hydroxy B - nor - androstane - 3,17 - dione -#6 - methylene - B - nor - androst - 4 - ene- 3,17 - dione-#6,6 - ethylene - B - nor - androst- 4 - ene - 3,17 - dione-#6,6 - ethylene - B - norandrost - 4 - ene - 3#,17# - diol-#required compound. 17# - Hydroxy - 6,17α - dimethyl B - norandrost - 4 - en - 3 - one and 17# - hydroxy- 17α - ethyl - 6 - methyl - B - nor - androst - 4 - en- 3-one are prepared by hydrogenation of the corresponding 6-methylene compounds. Pharmaceutical compositions suitable for oral or topical administration in the treatment of conditions caused by hyperandrogenicity, such as acne and hirsutism, comprise a compound of Formula (I) or 17-ester thereof and a pharmaceutical carrier, and may be in the form of a sesame oil suspension for oral use or a cream for topical use. |
