Patent GB-831885-A (GB)
Title: Substituted nitro-quinolones
Inventor: HEPWORTH WALTER
IPC: C07D215/38
Filed: 1957-03-22
Abstract: The invention comprises compounds, and their acid addition salts, of the general formula <FORM:0831885/IV (b)/1> wherein R represents an alkyl radical, R1 a hydrogen atom or an alkyl radical, and R2 an amino or a substituted amino group (including alkyl-, dialkyl- and acyl-amino, arylsulphonyl-amino optionally substituted by amino or acyl-amino radicals, and guanidino radicals, optionally substituted by acyl radicals), and the preparation thereof (wherein R2 represents an amino group) by hydrolysis of the corresponding quinoline wherein R2 represents an acyl-amino group; (where R2 represents a substituted amino group which is not substantially harmed by nitrating conditions) by nitrating a quinoline unsubstituted in the 6-position, and (where R2 represents an alkoxycarbonyl amino group) by thermal decomposition in the presence of an alcohol of the corresponding 3-azidocarbonylquinolone.  Those of the quinolones of the invention, wherein R2 represents an amino group may also be prepared by subjecting the corresponding quinolones wherein the 3-position is substituted by a suitable derivative of the carboxy group to either the Hofmann or Curtius reactions; and those wherein R2 represents a substituted amino may be prepared from the corresponding quinolone derivatives of the invention wherein R2 represents an amino group by known standard procedures, e.g. alkylation, acylation and condensation.  The compounds of the invention may further be prepared by alkylation of 4-hydroxyquinoline derivatives of the formula <FORM:0831885/IV (b)/2> The Provisional Specification relates to compounds of the general formula <FORM:0831885/IV (b)/3> wherein the ring A may bear one or more substituents, R represents an alkyl or alkenyl radical, optionally substituted, R1 a hydrogen atom or a hydrocarbon radical, optionally substituted, and R2 an amino or substituted amino group or a precursor thereof.  3 - (N - Methylacetamido) - 1 - methyl - 4 - quinolone is prepared by treating 3-amino-1-methyl-4-quinolone with p-toluene sulphonyl chloride to give 1-methyl-3-(p-toluenesulphonamido)-4-quinoline, methylating this to give 1 - methyl) - 3 - (N - methyl - p - toluenesulphonamido)-4-quinolone, followed by hydrolysis to 1-methyl-3-methylamino-4-quinolone and acetylation; 3 - dimethylamino - 1 - methyl - 4 - quinolone by methylation of 3-amino-1-methylquinolone with hydrogen and formaldehyde; and 3 - acetamido - 1 - ethyl - 4 - quinolone from 1-ethyl-3-nitro-4-quinolone by reduction to 1-ethyl-3-amino-4-quinolone and acetylation.ALSO:Pharmaceutical compositions comprise compounds of the general formula <FORM:0831885/VI/1> and acid addition salts thereof, wherein R stands for an alkyl radical, R1 for a hydrogen atom or an alkyl radical, and R2 for an amino or substituted amino group (including alkyl-, di-alkyl- and acyl-amino radicals, arylsulphonylamino radicals optionally substituted by amino or acylamino radicals, and guanidino radicals optionally substituted by acyl radicals) together with a diluent or a carrier therefor, the said compositions optionally containing other known therapeutic agents. The compositions iclnude aqueous and non-aqueous solutions and suspensions, dispersible powders and granules, cream and ointments, tablets, pills, pessaries and bougies.