GB1448980A - Unsymmetrically substituted bis-chromones - Google Patents

Abstract

1448980 Bis-chromone derivatives FISONS Ltd 18 Dec 1973 [19 Jan 1973 (2)] 2861/73 and 2862/73 Heading C2C The invention comprises novel compounds of the Formula I: in which R 1 to R 6 each are hydrogen, halogen, hydroxy, alkyl, alkoxy or alkenyl, the alkyl and alkoxy groups optionally being substituted by hydroxy, alkoxy, halogen or phenyl, X is a C 2-10 hydrocarbon optionally interrupted by an oxygen atom and/or substituted by an OH group, Ra and Rb are different and are COOH, CONHOH or wherein alkyl, alkoxy, and alkenyl, unless otherwise specified, have up to 6 carbon atoms therein, or a pharmaceutically acceptable salt thereof. The compounds I may be prepared by (1) reacting a compound VI: or an ester thereof with a compound VII: or an ester thereof, wherein Y is hydrogen or a reactive metal when Z is Xb and Z represents hydrogen or a reactive metal when Y is Xb and Xb is a C 2-19 hydrocarbon group optionally interrupted by an oxygen atom and carrying an epoxide or an anion forming group which on reaction with hydrogen or a reactive metal yields a group X; (2) for producing a compound of the Formula Ib: (a) reacting a compound VIII: with an azide; (b) removing a group R 11 from a compound III or IV: in which R 11 is a group replaceable by hydrogen; (3) for producing a compound Ia: by selectively hydrolysing a compound carrying a group hydrolysable to COOH at the 2-position; (4) for producing a compound Ic: by reacting a mono-ester, anhydride or acid halide of a compound carrying a 2-COOH group with hydroxylamine to form the 2-CONHOH group; or (5) salt formation. 5 - [3 - (2 - Cyano - 4 - oxo - 4H - 1 - benzopyran - 5 - yloxy) - 2 - hydroxypropoxy] - 4 - oxo- 4H - 1 - benzopyran - 2 - carboxylic acid is prepared by reacting sodium 5-[3-(2-methoxycarbonyl - 4 - oxo - 4H - 1 - benzopyran - 5 - yloxy) - 2 - hydroxypropoxy] - 4 - oxo - 4H - 1- benzopyran - 2 - carboxylate with ammonia to yield sodium 5 - [3 - (2 - carbamoyl - 4 - oxo - 4H- 1 - benzopyran - 5 - yloxy) - 2 - hydroxypropoxy]- 4 - oxo - 4H - 1 - benzopyran - 2 - carboxylate followed by simultaneous dehydration of the carbamoyl group and conversion of the sodium salt to the free acid. Sodium 5 - [3 - (2 - methoxycarbonyl - 4 - oxo- 4H - 1 - benzopyran - 5 - yloxy) - 2 - hydroxypropoxy] - 4 - oxo - 4H - 1 - benzopyran - 2 - carboxylate is prepared by reacting the diethyl ester with methanolic sodium hydroxide. Pharmaceutical compositions of the compounds I with the usual excipients inhibit the release and/or action of pharmacological mediators which result from the in vivo combination of certain types of antibody and specific antigen when administered orally or by inhalation.