Patent GB-1504709-A (GB)
Title: N-substituted quinolinone-2-carboxyl. acid der
IPC: C07D221/08
Filed: 1974-12-07
Abstract: 1504709 N-substituted quinolinone-2-carboxylic acid derivatives FISONS Ltd 21 Nov 1975 [7 Dec 1974 (3)] 53005/74 53010/74 and 53011/74 Heading C2C Novel compounds of the Formula I in which R 5 , R 6 , R 7  and R 8 , which may be the same or different, each represent hydrogen, alkyl, halogen, hydroxy, alkenyl, phenyl, alkoxy, alkenyloxy or phenylalkoxy; the alkyl, alkenyl, phenyl, alkoxy, alkenyloxy and phenylalkoxy groups optionally being substituted by a hydroxy, alkoxy, phenyl or halo group or by a 5- or 6-membered heterocyclic ring containing carbon and oxygen, or an adjacent pair of R 5 , R 6 , R 7  and R 8  form a chain  or, 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 7  and R 8  form a group of Formula II, in which Ra, Rb and Rc have the same significances as R 5 , R 6 , R 7  and R 8 , save that none of Ra, Rb, and Rc can form a group of Formula II, nor can an adjacent-pair of Ra, Rb and Rc form a chain -COCH=C(COOH)NRh-, nor can an adjacent pair of Ra, Rb, and Rc together with the adjacent carbon atoms in the benzene ring, form a 5- or 6-membered carbocyclic ring, X is a hydrocarbon chain which may be interrupted by one or more oxygen atoms or carbonyl groups, or which may be substituted by one or more hydroxy or alkoxy groups or by one or more halogen atoms, Rg and Rh, which may be the same or different are each alkyl, alkenyl, phenyl-alkyl, alkanoyl, benzoyl or phenylalkanoyl, or Rg and R 8  and/or Rh and Rc (Rc being in the 8-position) in Formula II, together form a chain -(CH 2 ) n -, and n is 2, 3 or 4, provided that-when Rg is methyl or ethyl not all of R 5 , R 6  R 7  and R 8  are hydrogen, and pharmaceutically acceptable salt, ester or amide thereof, may be prepared by (a) selectively hydrolysing or oxidizing a compound of Formula III in which Rg and the proviso are as defined above, R 5 a, R 6 a, R 7 a and R 8 a have the same significances as R 5 , R 6 , R 7  and R 8  above, save that an adjacent pair of R 5 a, R 6 a, R 7 a and R 8 a may represent a chain of formula in which Rh is as defined above, or one of R 5 a, R 6 a, R 7 a and R 8 a may represent a group of Formula IV in which X, Ra, Rb, Rc and Rh are as defined above, and D represents a group hydrolysable or oxidizable to a -COOH group, (b) producing a compound of Formula I in which ta least one of Rg and Rh is an alkyl or a phenyl-alkyl group, by selective reduction of a corresponding compound of Formula I, or an ester thereof, in which at least one of Rg and Rh is an alkenyl, alkanoyl or a phenyl-alkanoyl group, (c) (c) cyclizing a compound of Formula VIII or IX or an ester of either thereof, in which Rg and the proviso are as defined above, R 5 c, R 6 c, R 7 c and R 8 c have the same significances as R 5 , R 6 , R 7  and R 8  above, save that an adjacent pair of R 5 c, R 6 c, R 7 c and R 8 c may represent the pairs of groups -H and in which Rh is as defined above, or one of R 5 c, R 6 c, R 7 c and R 8 c may represent a group of Formula X or an ester thereof, in which X, Ra, Rb, Rc and Rh are as defined above, (d) producing a compound of Formula I in which X is a hydrocarbon chain optionally substituted by an -OH group, by reacting a compound of Formula XI or an ester thereof, in which Ra, Rb, Rc and Rh are as defined above, and Z is hydrogen or a metallic cation, or is a hydrocarbon chain carrying an anion forming group or an epoxide group, with a compound of Formula XII or an ester thereof, in which R 5 , R 6 , R 8  and R 8  are as defined above, and Y represents hydrogen or a metallic cation when Z represents a hydrocarbon chain carrying an anion forming group or an epoxide group, and, when Z represents hydrogen or a metallic cation, Y represents a hydrocarbon chain carrying an anion forming group or an epoxide group, or (e) cyclizing a compound of Formula XV in which Rg is as defined above, R<SP>11</SP> is an -OH group or a group hydrolysable thereto, R 5 d, R 6 d, R 7 d and R 8 d have the same significances as R 5 , R 6 , R 7  and R 8  above, save that an adjacent pair of R 5 d, R 6 d, R 7 d and R 8 d may represent the pair of groups -NHRh and -COCH 2 COCOR<SP>11</SP>, in which Rh and R<SP>11</SP> are as defined above, or one of R 5 d, R 6 d, R 7 d and R 8 d may represent a group of Formula XVI in which Ra, Rb, Rc, Rh and R<SP>11</SP> are as defined above, and where desired or necessary converting the compound of Formula I to pharmaceutically acceptable amide, ester or salt or vice-versa. Dimethyl 2 - [N - ethyl - N - (3 - hydroxy - 4- propyl - 5,6,7,8 - tetrahydro - 1 - naphthyl)amino] fumarate and the corresponding maleate are prepared as a mixture by reacting 1-ethylamino- 3 - hydroxy - 4 - propyl - 5,6,7,8 - tetrahydronaphthalene with dimethyl acetylene dicarboxylate in the presence of benzyl trimethyl ammonium hydroxide. Pharmaceutical compositions of the compounds I with the usual excipients show activity against diseases resulting from antibodyantigen reaction when administered orally, topically or by inhalation.