Patent GB-780915-A (GB)
Title: Cyclopentanopolyhydrophenanthrene compounds and pharmaceutical compositions containing them
IPC: C07J75/00
Filed: 1955-12-05
Abstract: The invention comprises allopregnanes of the general formula <FORM:0780915/IV (a)/1> wherein R represents =O, or <FORM:0780915/IV (a)/2> represents hydrogen or a hydroxy group or ester thereof, and X represents a halogen, and the preparation thereof by hydrogenating the corresponding D 4-pregnene in the presence of a hydrogenation catalyst such as Raney nickel or palladium supported on a carbon carrier.  The 21 - hydroxy - allopregnanes prepared by the above process may be acylated to form the corresponding 21-acyloxy-allopregnanes, e.g. in the presence of an organic base including pyridine and alkyl derivatives thereof and tertiary bases such as dialkyl-anilines, quinolines and trialkylamines, suitable acylating agents being aliphatic acid halides, anhydrides and esters and aliphatic ketenes.  The hydrogenation may be carried out at approximately atmospheric, sub-atmospheric or super-atmospheric pressure, preferably at a room temperature such as at approximately 25 DEG  to 30 DEG  C.  An organic solvent such as ethyl acetate, methanol, ethanol, isopropyl alcohol, benzene, acetone or ethyl ether may be used in the hydrogenation step.  A suitable quantity of hydrogenation catalyst is from about 5 to 150 per cent by weight based on the weight of D 4-pregnene reactant.  The group X may be fluorine, bromine, chlorine or iodine.  The 21-ester-allopregnanes preferably contain from 1 to 8 carbon atoms in the ester group, e.g. the allopregnane may be a 21-acetate, -propionate, -formate, -butyrate, -benzoate, - t - butylacetate, - hemi - succinate, or -phenylacetate.  The Specification refers specifically to the following compounds: 9a -fluoro-allopregnane - 11b ,21 - diol - 3,20 - dione and the 21-phosphate, -acetate, -propionate, -butyrate, -hemisuccinate, -t-butylacetate, -phenylacetate and -benzoate thereof, 9a -chloro-allopregnane - 11b ,21 - diol - 3,20 - dione and the 21-acetate and -benzoate thereof, 9a -bromo-allopregnane - 11b ,21 - diol - 3,20 - dione and the 21-acetate thereof, 9a -fluoro-allopregnane-21 - ol - 3,11,20 - trione and the 21 - phosphate and -acetate thereof, 9a -iodo-allopregnane-11b ,21-diol-3,20-dione, 9a -bromo (and chloro and iodo)-allopregnane-21-ol-3,11,20-trione, 9a -fluoro (and chloro and bromo)-allopregnane-11b  - ol - 3,20 - dione, and 9a  - fluoro - allopregnane-3,11,20-trione.  A number of detailed examples are given.ALSO:A pharmaceutical preparation contains as the active ingredient a cyclopentanopolyhydrophenanthrene compound of the general formula <FORM:0780915/VI/1> wherein R represents = O, or <FORM:0780915/VI/2> , X represents a halogen, and R1 represents hydrogen or a hydroxy group or an ester group derived therefrom.  In an example, a topical ointment is prepared containing 9 a -fluoro-allopregnane-11b , 21-diol-3,20-dione 21-acetate, zinc stearate, 1,3-propylene glycol, a polyethylene glycol and water. The cyclopentano-polyhydrophenanthrene compound in this preparation may be replaced by 9 a -fluoro-allopregnane-11b ,21-diol-3,20-dione or the 21-t-butylacetate thereof, 9a  - chloro - allopregnane - 11b , 21 - diol - 3, 20-dione or the 21-benzoate thereof, 9a -bromo-allopregnane - 11b , 21 - diol - 3,20 - dione or the 21-benzoate thereof, 9a -bromo-allopregnane-11b ,21 - diol - 3,20 - dione 21 - acetate or 9a -fluoro - allopregnane - 11b  - ol - 3,20 - dione.