Patent GB-1497829-A (GB)
Title: 11-deoxyprostaglandins
IPC: A61K31/23
Filed: 1975-04-21
Abstract: 1497829 11-Deoxyprostaglandins MAY & BAKER Ltd 20 April 1976 [21 April 1975] 16429/75 Heading C2C [Also in Division C3] The invention comprises 11-deoxyprostaglandins of the formula wherein R<SP>1</SP> is H or C 1-15  alkyl; A is C 1-12  alkylene; Y is carbonyl or hydroxymethylene, n is 4, 5 or 6 and either (i) Z is a direct bond and R<SP>7</SP> is H or alkyl or an aryl or heteroaryl which may be substituted by one or more substituents selected from halogen atoms, alkyl, haloalkyl, alkenyl, alkoxy, alkenyloxy, alkoxycarbonyl, hydroxy, cyano, nitro, sulphamoyl, mono- or di-alkyl sulphamoyl, carbamoyl, mono- or dialkylcarbamoyl and dialkylamino, or else (ii) Z is O or S, and R<SP>2</SP> is alkyl or an aryl or heteroaryl group which may be substituted by one or more substitutents selected from halogen atom, alkyl, haloalkyl, alkenyl, alkoxy, alkenyloxy, alkoxycarbonyl, hydroxy, cyano, nitro, sulphamoyl, mono- or di-alkyl sulphomoyl, carbamoyl, mono- or di-alkylcarbamoyl, alkanoylamino and dialkylamino, and the vinylene groups in the side-chains are both in transconfiguration and cyclodextrin clathrates thereof and when R<SP>1</SP> is H, non-toxic salts thereof, and their preparation. The compounds of the above Formula I in which Y is hydroxymethylene are prepared by reducing the corresponding compounds in which Y is carbonyl, which are obtained by hydrolysing compounds of the Formula V wherein the symbols R<SP>4</SP> are identical alkyl groups or together form an ethylene linkage optionally substituted by one identical alkyl group on each carbon atom. The free acids may be obtained by the hydrolysis of the corresponding C 1-15  alkyl esters and the esters prepared by esterification of the appropriate acids. The following intermediates are also prepared: 6 - (7 - hydroxyheptyl) - 7 - (3 - oxooct - trans- 1 - enyl) - 1,4 - dioxaspiro[4,4]nonane; 6 - (7- hydroxyheplyl) - 7 - [3 - oxo - 4 - phenoxy (or p - chlorophenoxy) - but - trans - 1 - enyl] - 1,4- dioxaspiro[4,4]nonane; 6 - (6 - formylhexyl) - 7 - (3 - oxooct - trans - 1 - enyl) - 1,4 - dioxaspiro- [4,4]nonane; 6 - (6 - formylhexyl) - 7 - [3 - oxo- 4 - phenoxy (or p - chlorophenoxy) - but - trans - 1 - enyl] - 1,4 - dioxaspiro[4,4] - nonane; 6 - (8 - ethoxycarbonyl - oct - trans - 7 - enyl)- 7 - (3 - oxooct - trans - 1 - enyl) - 1,4 - dioxaspiro[4,4]nonane; 6 - (8 - ethoxycarbonylocttrans - 1 - enyl) - 7 - [3 - oxo - 4 - phenoxy (or p - chlorophenoxy) - but - trans - 1 - enyl] - 1,4- dioxaspiro[4,4]nonane; compounds of Formula V above; and 1-chloro-3-(p-chlorophenoxy)- acetone. 3 - (p - Chlorophenoxy) - 2 - oxopropylidene triphenylphosphorane is prepared by adding aqueous sodium bicarbonate solution to 2-oxo- (p - chlorophenoxy)propyltriphenylphosphonium chloride, obtained by reacting 1-chloro-3-(pchlorophenoxy) acetone with triphenylphosphine Pharmaceutical compositions, suitable for oral, rectal, vaginal or perenteral administration, contain the above 11-deoxyprostaglandins or non-toxic salts thereof or cyclodestrin clathrates thereof together with pharmaceutical carriers or coatings. The compounds possess similar pharmacological properties to the naturally occurring prostaglandins.