Patent GB-1447480-A (GB)
Title: Chromone and thiachromone carboxamide tetrazoles
IPC: C07D409/12
Filed: 1973-08-17
Abstract: 1447480 (Thio)chromone-carboxamido-tetrazoles FISONS Ltd 29 Nov 1973 [15 Dec 1972 17 Aug 1973 (4)] 56070/73 Divided out of 1447479 Heading C2C Novel compounds of Formula (I) in which R 5 , R 6 , R, and R 8 , which may be the same or different, each represent hydrogen, alkyl, halogen, hydroxy, alkenyl, phenyl, alkoxy, alkenyloxy, phenoxyalkoxy, or phenphenylalkoxy, these groups, where possible, being optionally substituted by hydroxy, alkoxy, halo or a heterocyclic ring containing carbon and oxygen, or an adjacent pair of R 5 , R 6 , R 7  and R 8 , together with the adjacent carbon atoms in the benzene ring, form a 5 or 6-membered carbocyclic ring, or one of R 5 , R 6 , R, and R 8  represents a group of the formula XXI in which R 1 , R 2  and R 3  have the same meanings as R 5  to R 7  above, save that they do not denote a Formula XXI and that an adjacent pair of R 1  to R 3  do not form a ring with adjacent ring carbons, 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, each pair of R 9  and R 10  may be the same or different and are H, C 1-6  alkyl, C 2-6  alkenyl, phenyl- C 1-6  alkyl, C 2-6  alkanoyl or C 2-6  alkoxycarbonyl, and W is -O- or -S-, provided that when R 9  and R 10  are both H, R 5 , R 6 , R 7  and R 8  do not represent XXI and W is -O-, then (i) 3 or 4 of R 5  to R 8  are other than H, or (ii) at least one of R 5  to R 8  is alkenyl, phenyl or alkenyloxy, or an alkyl, alkenyl, phenyl, alkoxy, alkenyloxy, phenoxyalkoxy or phenylalkoxy substituted by a halo group or by a heterocyclic ring containing carbon and oxygen; or an alkyl, alkenyl, phenoxyalkoxy, phenylalkoxy or phenyl group each of which is substituted by a hydroxy or alkoxy group, or a pharmaceutically acceptable salt thereof, may be obtained by (a) removing a group R 11  from a compund of Formula (II) in which R 11  denotes a group which may be replaced by H, and R<SP>a</SP> 5  to R<SP>a</SP> 8  have the same meanings as R 5  to R 8 , same that one of them may denote a group III (b) by (i) removing a group R 12  from a compound of Formula (IV) in which R 12  denotes a group which may be replaced by H, and R<SP>a</SP> 5  to R<SP>a</SP> 8  have the same meanings as R 5  to R 8 , save that one may be a group of Formula (V) (ii) cyclizing a compound of Formula (VI) in which R<SP>c</SP> 5  to R<SP>c</SP> 8  can have the same meanings as R 5  to R 8 , save that one of them may denote a group of Formula (VII) (c) by reacting a compound of Formula (VIII) in which R<SP>j</SP> 5  to R<SP>j</SP> 8  have the same meanings as R 5  to R 8 , save that one can denote a group of the Formula (XXIV) or an acid halide, an ester or a mixed anhydride thereof, with a compound of the Formula (IX) (d) by cyclizing a compound of Formula (X) or an alkali metal salt thereof, in which R<SP>d</SP> 5  to R<SP>d</SP> 8  have the same meanings as R 5  to R 8 , save that one of them may denote a group of Formula (XI) or (e) selectively dehydrogenating a compound of the Formula (XII) in which R<SP>e</SP> 5  to R<SP>e</SP> 8  have the same meanings as R 5  to P 8 , save that one of them can have the Formula XIII and where desired or necessary converting the compound of Formula I to a pharmaceutically acceptable salt thereof. The preparation of the following intermediates is also described: 4-oxo-4H-1-benzopyran-2- [N - (1 benzyl - 4 - methyl - 2 - tetrazolin - 5- ylidene)]carboxamide; 2 - (4 - chlorophenoxy)- ethyl methanesulphonate; 6 - [2 - (4 chlorophenoxy)ethoxy] - 2 - hydroxy - 3 - n - propylacetophenone; 5 - [2 - (4 - chlorophenoxy)- ethoxy] - 4 - oxo - 8 - n - propyl - 4H - 1 - benzopyran - 2 - carboxylic acid; 5,51 - [(2 - formyloxytrimethylene)-dioxy]bis[5 - (4 - oxo - 4H- 1 - benzopyran - 2 - carboxylic acid] and corresponding acid chloride; Pharmaceutical composition, useful in treatment of asthma, comprises a compound of Formula I: or salt thereof, in admixture with a solid or liquid diluent, in forms for administration, orally, topically rectally or by inhalation.