1,4-dihydro-4-oxo-3-quinoline derivatives as selectively toxic mammalian antibacterial agents

DETAILED DESCRIPTION OF THE INVENTION Compounds of the formula I may be prepared as illustrated in the following reaction scheme.
##STR6## Referring to the above reaction scheme, compounds of the formula I, wherein Q is hydrogen and R and Y are as defined above, may be prepared by reacting a compound of the formula II, wherein R and Y are as defined above and Hal is chloro, bromo, fluoro or iodo, with a compound of the formula III.
The reaction may be performed in the absence of a solvent or in the presence of a polar, reaction inert solvent such as acetonitrile, tetrahydrofuran, ethanol, chloroform, dimethylformamide, pyridine, or water, or mixtures thereof.
The reaction is preferably carried out in the presence of a base such as an alkali metal or alkaline earth metal carbonate or bicarbonate, or a secondary or tertiary amine such as triethylamine, pyridine or picoline.
The preferred reaction temperature is from about 60.
degree.
to about 100.
degree.
C.
, but temperatures from about 10.
degree.
to about 150.
degree.
C.
are generally suitable.
The starting materials of formula II are known in the art, e.
g.
as disclosed in European Patent Application 0230295A2.
Compounds of the formula III, wherein Q is hydrogen, may be made as described in U.
S.
Pat.
No.
3,947,445 and in J.
Org.
Chem.
, 31, 1059 (1966).
Compounds of the formula I wherein Q is methyl may be prepared from the corresponding compounds of the formula I wherein Q is hydrogen by conventional methylation procedurs.
For example, one standard methylation procedure known in the art involves the use of formic acid and paraformaldehyde.
According to this procedure, a mixture of an alkali or alkaline earth metal formate (preferably sodium formate), formic acid (preferably 87% formic acid), formalin (preferably 37% formalin), and a compound of the formula I wherein Q is hydrogen are reacted to yield a compound of the formula I wherein Q is methyl.
The reaction is typically carried out by stirring the reactants for approximately 0.
5 to 24 hours, preferably about 2 hours, at a temperature of from about 80