Patent GB-1346724-A (GB)
Title: 1,4-dihydro-4-oxo-3-quinolinecarboxylic acids and esters and their preparation
IPC: A61K31/44
Filed: 1972-05-05
Abstract: 1346724 Dihydroquinoline-3-carboxylic acid derivatives STERLING DRUG Inc 5 May 1972 [17 May 1971] 21013/72 Heading C2C Novel 1-R 1 -1,4-dihydro-3-(COOR)-4-oxo-5 (or 6)-R<SP>1</SP>-7-PY-quinolines in which R 1  is 1-6 C alkyl, 2-6 C hydroxyalkyl, or 2-6 C haloalkyl; R is H, 1-6 C alkyl or CH 2 OAc where Ac is benzoyl or 1-6 C alkanoyl; R<SP>1</SP> is H, halo, 1-6 C alkyl or 1-6 C alkoxy; and PY is Q-1-(O) n -4(3 or 2)-pyridyl, Q-1-Q<SP>1</SP>-4(3 or 2). piperidyl or 1-(1-6 C alkyl)-1-2-dihydro-2-oxo- 4-pyridyl; n is 0 or 1; Q is H or 1-4 substituents, on available C atoms other than vicinal to the 7-quinoline carbon atom, which are selected from 1-6 C alkyl or alkoxy, halo, OH, 1-6 C alkanoyloxy, HOCH 2 , NH 2 CH 2 , (1-6 C alkanoyl) NHCH 2 , NH 2 , CHO, CN, CONH 2 , COOH and 2-7 C alkoxycarbonyl; and Q<SP>1</SP> is H or 1-6 C alkyl are prepared by alkylation at the 1-position of the corresponding 1,4-dihydro-3- (COOR) - 4 - oxo - 5(or 6) - R<SP>1</SP> - 7 - PY - quinolines where R is H or alkyl, PY is Q-1-(O) n - 4(3 or 2)-pyridyl and Q is other than NH 2 CH 2  or NH 2 ; and where PY is Q-1-Q<SP>1</SP>-4(3 or 2)- piperidyl the resulting compound is reduced. Where it is desired to prepare the compound where PY is 1-alkyl-1,2-dihydro-2-oxo-4- pyridyl or Q-1-Q<SP>1</SP>-4(3 or 2)-piperidyl where Q<SP>1</SP> is alkyl a free base obtained where PY is Q-4(3 or 2)-pyridyl is quaternized and then either oxidized or reduced respectively. The N- oxides are prepared conventionally by oxidation. Other conversions, well known in the art, may be effected to give other of the novel compounds. Intermediates isolated are 4-(3-aminophenyl) pyridine; diethyl 3-(4,3 or 2-pyridyl)anilinomethylene malonate and similar compounds which are substituted in the pyridine nucleus; 2,6 - dimethyl - 4 - (3 - nitrophenyl) - pyridine- N - oxide; 6 - methyl - 4 - (3 - nitrophenyl)- pyridine - 2 - methanol; 6 - methyl - 4 - (3- nitrophenyl) - pyridine - 2 aldehyde; 2- methyl - 4 - (3 - nitrophenyl) - pyridine; 4 - (3- aminophenyl) - 2 - methylpyridine; 2 - hydroxy- 6 - methyl - 4 - (3 - nitrophenyl)pyridine; 4 - (3 - aminophenyl) - 2 - hydroxy - 6 - methylpyridine; diethyl 2,6-diethyl-1,4-dihydro-4-(3- nitrophenyl) - 3,5 - pyridine - dicarboxylate; diethyl 2,6 - diethyl - 4 - (3 - nitrophenyl) - 3,5- pyridinedicarboxylate, and the corresponding acid; 2,6-diethyl-4-(3-nitrophenyl)-pyri 2 ine; 4- (3-aminophenyl)-2,6-diethyl pyridine; 3,6-dimethyl - 4 - (3 - nitrophenyl) - 2(1H) - pyridine; 2 - chloro - 3,6 - dimethyl - 4 - (3 - nitrophenyl)- pyridine; 4-(3-aminophenyl)-2,5-dimethyl pyridine ; 6 - hydroxy - 2,3 - dimethyl - 4 - (3 - nitrophenyl) - pyridine; 6 - chloro - 2,3 - dimethyl- 4 - (3 - nitrophenyl) - pyridine; 4 - (3 - aminophenyl) - 2,3 - dimethylpyridine; 2 - (3 - nitrobenzoyl)butyronitrile; 3,5,6 - trimethyl - 4 - (3- nitrophenyl)-2(1H)-pyridine; 2-chloro-3,5,6-trimethyl-4-(3-nitrophenyl)-pyridine; 4-(3-aminophenyl) - 2,3,5 - trimethylpyridine; 2,6 - bis - (2- furyl)-3-methyl-4-(3-nitrophenyl)-pyridine; 3- methyl - 4 - (3 - nitrophenyl) - 2,6 - pyridinedicarboxylic acid; 3-methyl-4-(3-nitrophenyl) pyridine; 4-(3-aminophenyl)-3-methylpyridine; dimethyl 1,4-dihydro-4-(2-methoxy-5-nitro-phenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate; dimethyl 4-(2-methoxy-5-nitrophenyl)-2,6-dimethyl-3,5-pyridine dicarboxylate, and the free acid; 4-(2-methoxy-5-nitrophenyl)-2,6-dimethyl pyridine; 4 - (5 - amino - 2 - methoxyphenyl)- 2,6 - dimethyl - pyridine HCl; dimethyl 4- (2 - fluoro - 5 - nitrophenyl) - 1,4 - dihydro - 2,6- dimethyl - 3,5 - pyridinedicarboxylate; dimethyl 4 - (2 - fluoro - 5 - nitrophenyl) - 2,6- dimethyl - 3,5 - dicarboxylate; and dimethyl 4 - (2 - fluoro - 5 - amino) - 2,6 - dimethyl - 3,5- dicarboxylate. Pharmaceutical compositions comprise one of the novel compounds together with a diluent or carrier and are administered orally or parenterally as antibacterial agents.