Substituted bis-(2-carboxy-chromonyl-oxy) derivatives and preparation and pharmaceutical compositions thereof

摘要

1,144,905. Chromone derivatives. FISONS PHARMACEUTICALS Ltd. 3 March, 1966 [25 March, 1965; 9 Dec., 1965; 17 Dec., 1965], Nos. 12626/65, 52414/65 and 53744/65. Heading C2C. [Also in Division A5] The invention comprises bis-chromonyl compounds of the formula and functional derivatives of carboxylic acid groups present in which R1, R2, R3, R4, R5 and R6 are the same or are different and each is a hydrogen or halogen atom or a hydroxy, alkyl, alkoxy, or substituted alkyl or alkoxy group and X is a saturated or unsaturated, substituted or unsubstituted, straight or branched hydrocarbon chain which may be interrupted by a carbocyclic or heterocyclic ring or one or more oxygen atoms or carbonyl groups, which are prepared by reacting in one or more stages a compound and a compound A-X1-B, in which Z is a hydroxy group and Y a hydrogen atom, a group -COCH 3 , or -COOR1 (in which R1 is an alkyl group), or Y and Z together form a chain (W is a carboxylic group or derivative or a group convertible thereto); Y1 and Z1 have the same meaning as Y and Z and may be the same as or different from Y and Z; A and B are the same or are different and each is a group capable of reacting with a hydroxyl group to form an ether linkage, or one of A and B is a group capable of being converted to such a reactive group; and X1 is such that the group (in which A1 and B1 are the residues of A and B after the formation of ether linkages has the same meaning as X and thereafter converting Z and Y and Z1 and Y1 to chains or functional derivatives thereof to form the bis-(chromone-2-carboxylic acid). A preferred compound is 1,3-bis-(2-carboxychromon-5-yloxy)-2-hydroxypropane and many other compounds are claimed. Salts of the compounds with suitable cations, such as alkali and alkaline earth metals and organic bases are also described. Several embodiments of the preparation are described, for example the reaction of o-hydroxy-acetophenone with an oxalic acid derivative of formula in which R9 is a halogen atom or a group -OR1 (R1 is alkyl) R10 and R11 are both halogens and R12 is a group OR1 or R10 and R11 together represent a carbonyl oxygen atom and R12 is a halogen or -OR1. The compounds are used in pharmaceutical compositions in the treatment of asthma (see Division A5).