(1H-tetrazol-5-yl)-2(1H)-quinolinones and-naphthyridones and antiallergic use thereof

#The present invention is directed to a group of 2(1H)-quinolinones having a tetrazole substituent at the 3- or 4-position. More particularly, it relates to compounds having the following general formula: ##STR1## wherein A is --CH.dbd.or --N.dbd.; R is H or alkyl of 1-4C; n is 0, 1 or 2; X is H, alkyl of 1-4C, alkoxy of 1-4C, halogen, methylmercapto, methylsulfonyl, or two X's can be combined as methylenedioxy; with the proviso that, when X is methylmercapto or methylsulfonyl, then n must be 1; and the pharmaceutically acceptable salts thereof.

#The substituent with the free valence entering the ring between the positions marked as 3 and 4 can only be attached to either of those two positions. The X substituent can only be attached at available 6-, 7 -and/or 8-positions in the left hand ring in the structure shown above. Halogen is fluorine, chlorine or bromine. Examples of the alkyl groups are methyl, ethyl, propyl or isopropyl; examples of the alkoxy groups are methoxy, ethoxy, propoxy, isopropoxy or butoxy.

#Preferred compounds are those in which the tetrazole substituent is attached at the 3-position of the quinolinone.

#To a mixture of 11880 ml of phosphoryl chloride and 2500 g of acetanilide was added, with cooling and stirring in an ice bath, 3380 g of dimethylformamide at such a rate that the temperature did not exceed 60.degree. C. The addition took about 45 minutes, at which time the cooling bath was removed and the mixture was heated to 75.degree. C. for 22 hours. The mixture was then cooled and the excess phosphoryl chloride was removed by rotary evaporation. The residual dark brown oil was then poured into about 32 liters of water with stirring. Ice was added to the aqueous mixture to keep the temperature below 50.degree. C. The dark yellow solid which formed was separated by filtration and dried in a forced-air oven at 70.degree. C. to give 2-chloro-3-quinolinecarboxaldehyde melting at about 145.degree.-147.degree. C.

#To the mixture obtained by the addition of 210 g of 4-(methylthio)acetanilide to 1246 g of phosphoryl chloride there was added 254 g of dimethylformamide over a period of 30 minutes with stirring. The reaction was exothermic and the rate of addition was controlled so that the temperature did not exceed 75.degree. C. After the addition was complete, the reaction was heated at 75.degree. C. for 2.5 hours. The mixture was then quenched in water and the yellow precipitate which formed was separated by filtration and dried to give 2-chloro-6-methylthio-3-quinolinecarboxaldehyde.

#When the above procedure was repeated using the appropriate substituted acetanilide, the following products were obtained: