GB867208A - 18-nor-steroids and d-homo-steroids - Google Patents

Abstract

The invention comprises compounds of the general formula: <FORM:0867208/IV (b)/1> in which n is 2 or 3, R1 is a free or functionally converted hydroxyl or oxo group, e.g. an esterified or etherified hydroxyl group or a ketalised oxo group, and R2 is a free or functionally converted carboxyl group, e.g. an esterified carboxyl group, a nitrile or amide group, or an acetyl or hydroxyacetyl group with a free or substituted especially esterified hydroxyl group, also the corresponding compounds having one double bond involving the 5-carbon atom, or having two double bonds, one involving the 5-carbon atom and the other in the 13:17-position. The compounds are prepared by cyclisation of compounds of the general formula: <FORM:0867208/IV (b)/2> preferably in the presence of a condensing agent, e.g. alkali metal hydroxides, alcoholates, amides or hydrides, or a dehydrating agent, e.g. piperidine acetate or benzoate or triethylamine benzoate in an inert solvent, followed if necessary by reduction of the 13-17-double bond, e.g. by catalytic hydrogenation. Subsequent modification of the radical R2 may be carried out, e.g. conversion of a free or functionally converted carboxyl group into the acetyl or hydroxyacetyl group, or esterification of a hydroxyl group. Examples detail the preparation of 18-norprogesterone, its 3-ketal, the 3-ketals of 13: 17-dehydro-18-norprogesterone, D 4, 13(17)-18-noretiadienic acid nitrile and of D 4. 13(17a)-20-oxo-18-nor-D-homopregnadiene. The starting materials of Formula II above can be prepared from the corresponding 2-methylene hydrophenanthrenes by oxidative splitting of the methylene double bond. Specification 845,283 is referred to.ALSO:Pharmaceutical preparations comprise compounds of the general formula <FORM:0867208/VI/1> in which n is 2 or 3, R1 is a free or functionally converted hydroxyl or oxo group, and R2 is a free or functionally converted carboxyl group and the corresponding compounds unsaturated at position 4 : 5, 5 : 6 and/or 13 : 17 or 17a (which compounds exhibit a progestative effect) together with a non-toxic solid or liquid carrier suitable for enteral, parenteral or local application. The compositions may be in the form of tablets, dragees, salves, creams, solutions, suspensions or emulsions and may contain auxiliaries such as preservatives, stabilizing, wetting or emulsifying agents, osmotic agents or buffers, together with other therapeutic compounds.