ANALOGHI DI 2 3 4 TRINOR 1 5 INTERM FENILENE PROSTACICLINA I2 PROCEDIMENTO PER LA LORO PREPARAZIONE E COMPOSIZIONI FARMACEUTICHE CHE LICONTENGONO

Inter-m-phenylene PFI2 derivs. of formula (I) and their pharmaceutically acceptable cationic salts are new, (A is carboxy, cyano, tetrazolyl, COOR3 or CONR1R2; B is oxygen or methylene; Y is opt. bromo substd. vinylene or -C(triple bond)C-. R4 is H or tetrahydropyran-2-yl. R5 is 5-9C alkyl opt. substd. by 1 or more oxygen, or CH=CH or -C(triple bond)C- and/or opt. substd. by halo; or it is phenoxymethyl (opt. substd. by halo or trifluoromethyl) or 3-5C alkenoyloxymethyl. R6 is H or 1-4C alkyl. R7 is H, halo, cyano, or 1-4C alkyl or alkoxy. R8 is H, halo, cyano, nitro, hydroxy or 2-5C alkanoylamino. R3 is 1-4C alkyl or the equiv. of a pharmacologically acceptable cation. R1 and R2 are each H, phenyl, 1-5C alkyl (opt. substd. by carboxy, hydroxy, phenyl or 2-5C alkoxycarbonyl) or 1-4C alkylsulphonyl, or together they represent a 3-6C, alpha-omega alkylene. If R5 is unsubstd. or uninterrupted 5-9C alkyl, CH=CH, -C(triple bond)C- or opt. substd.phenoxymethyl, then either R7 or R8 is other than H and A is other than carboxy or COOR3). They are made e.g. when B is oxygen, by reacting the appropriate lactol with a triphenylphosphorane; cyclising the PGF2 alpha deriv. formed with an electrophile, then elimination to form the exocyclic double bond. Compared with known PGI derivs. (I) have longer lasting and stronger cytoprotective and platelet aggregation inhibiting effects and better stability (sufficient for formulation of saline solns.). Particular uses are as antithrombotics (in vivo and in vitro); treatment of peripheral vascular disorders; inhibitors of gastric acid secretion and ulcer formation (including counteracting the effects of antiinflammatories which inhibit prostaglandin synthetase); bronchodilators, bronchospasmolytics, and inhibiting the effect of mediators such as slow reacting substance of anaphylaxis. They have only a low hypotensive effect.