Patent GB-780916-A (GB)
Title: Cyclopentanopolyhydrophenanthrene compounds and pharmaceutical compositions containing them
IPC: C07J75/00
Filed: 1955-12-06
Abstract: The invention comprises allopregnanes of the general formula <FORM:0780916/IV (a)/1> wherein R represents <FORM:0780916/IV (a)/2> represents hydrogen or a hydroxy group or an ester group derived therefrom, and X represents a halogen, and the preparation thereof by hydrogenating the corresponding D 5-pregnene in the presence of a hydrogenation catalyst such a Raney nickel or palladium supported on a charcoal 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 dialkylanilines, 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.  Organic solvents 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 - 17a ,21-diol-3,11,20-trione and the 21-acetate and -phosphate thereof, 9a - fluoro - allopregnane-11b ,17a ,21 - triol - 3,20 - dione and the 21-phosphate, -acetate, -propionate, -butyrate, -hemisuccinate, -t-butylacetate, -phenylacetate, and -benzoate thereof, 9a -chloro-allopregnane-11b ,17a ,21 - triol - 3,20 - dione and the 21-acetate thereof, 9a  - bromo - allopregnane-11b ,17a ,21 - triol - 3,20 - dione and the 21-acetate thereof, 9a -fluoro (chloro and bromo)-allopregnane - 11b ,17a  - diol - 3,20 - dione, 9a -fluoro - allopregnane - 17a  - ol - 3,11,20 - trione, 9a -chloro (and bromo and iodo)-17a ,21-diol-3,11,20 - trione, and 9a  - iodo - allopregnane - 11b ,17a ,21-triol-3,20-dione.  A number of detailed examples are given.ALSO:A pharmaceutical preparation contains as the active ingredient a cyclopentanopoly-hydrophenanthrene compound of the formula <FORM:0780916/VI/1> wherein R represents = O, or <FORM:0780916/VI/2> R1 represents hydrogen or a hydroxy group or an ester group derived therefrom, and X represents a halogen.  In an example a topical ointment is prepared containing 9a -fluoro-allopregnane-11b , 17a ,21-triol-3,20-dione 21-acetate, zinc stearate, 1,3-propylene glycol, a polyethylene glycol and p  water. The cyclopentanopolyhydrophenanthrene compound in this preparation may be replaced by the 21-acetate of 9a -chloro (or bromo) - allopregnane - 11b ,17a ,21 - triol - 3,20-dione, 9a  - fluoro - allopregnane - 17a ,21 - diol-3,11,20 - trione, or 9a  - fluoro - allopregnane-11b ,17a -diol-3,20-dione.