GB959378A — 21-substituted 17ª‡, 21-dioxy steroids and processes for their preparation

USPTO Abstract

The invention comprises 17a , 21-dihydroxysteroids having at the 17-position the general formula: <FORM:0959378/C2/1> wherein R1 represents hydrogen or an acyl group, and either B represents an alkyl or alkanoyl group containing up to 8 carbon atoms or an aralkyl group, or the hydrogen at the 21-position is absent and B then represents an alkylidene group containing up to 8 carbon atoms or an aralkylidene group, and the preparation thereof by acid hydrolysing the corresponding steroids having at the 17-position the general formula: <FORM:0959378/C2/2> wherein B has the above significance and R and R1 represent an aralkyl group or an alkyl group containing up to 8 carbon atoms or together represent a cycloaliphatic ring and when required, acylating the 21-hydroxy group. The steroids having at the 17-position the first formula above may contain oxo groups at the 3- and/or 11-positions, halogen at one or more of the 2-, 4-, 6-, 9-, 11- and 12-positions, alkyl groups at one or more of the 2-, 6- and 16-positions, hydroxy groups at one or more of the 1-, 2-, 3-, 11- and 12-positions, and unsaturation at one or more of the 1-, 4-, 5-, 6-, 7- and 9-positions. Typical compounds are of the general formula: <FORM:0959378/C2/3> and the corresponding 1, 2-dihydro compounds, wherein A represents hydrogen or a methyl group, Z represents halogen or hydrogen, or a methyl group, D represents an alkyl or alkylidene group containing up to 8 carbon atoms, Y represents O, (H,OH), (H,O-Acy) or (H, Halogen) except that when Y represents halogen X also represents halogen, R1 represents hydrogen or an acyl group, and B has the above significance. In the examples 21-methyl-prednisolone and 9a -fluoro-16a , 21-dimethyl-prednisolone and the corresponding 21-acetates are prepared by acid hydrolysing the corresponding 17a , 21-isopropylidenedioxy compounds and acetylating the products to form the 21-acetates; and 9a -chloro -21- methylene-1, 4-pregnadiene-11b , 17a , 21-triol-3, 20-dione 11b -formate and the corresponding 21-acetate are prepared by treating 17a , 21-isopropylidene-dioxy-1, 4, 9 (11)- pregnatriene-3, 20-dione with formaldehyde to form the corresponding 21-methylene compound, acid hydrolysing this compound to form 21-methylene -1, 4, 9 (11)-pregnatriene-17a , 21-diol-3, 20-dione, acetylating this compound to form the corresponding 21-acetate, treating the 21-acetate with N-chlorosuccinimide to form 9a -chloro-21-methylene-1, 4-pregnadiene-11b , 17a , 21-triol-3, 20-dione 11b -formate 21-acetate, and hydrolysing this compound with methanolic perchloric acid to form the corresponding 11b -formate-21-ol. Therapeutic compositions, which may be administered in forms such as creams, unguents, tablets and elixirs for the treatment of inflammatory diseases, contain steroid compounds having at the 17-position the first general formula above.