Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Heterocyclic carbon compounds containing a hetero ring...
Patent
1984-12-06
1987-09-15
Hollrah, Glennon H.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Heterocyclic carbon compounds containing a hetero ring...
514186, 514253, 514259, 514269, 514274, 514310, 544225, 544284, 544315, 544318, 544319, 544333, 544405, 546 2, 546143, A61K 3147, A61K 31505, C07D40104
Patent
active
046940006
DESCRIPTION:
BRIEF SUMMARY
The invention relates to novel therapeutically useful quinazoline and isoquinoline derivatives, to processes for the preparation of these derivatives and to pharmaceutical preparations which contain these derivatives as the active constituent.
The quinazoline and isoquinoline derivatives according to the present invention are characterized by the general formula I: ##STR2## and acid addition salts thereof, wherein X represents nitrogen or a CH-group, or trifluoromethyl, substituted by halogen, alkoxy(1-6C) or phenyl groups, a cyclic alkyl group or a substituted or unsubstituted aromatic group.
The compounds according to the general formula I have a biocidal action, in particular against Gram-positive bacteria, protozoa (such as Trichomonas pulmonalis and Trichomonas vaginalis) and above all pleuropneumonia-type microorganisms, such as mycoplasms, which inter alia can be responsible for the occurrence of pneumonia in cattle and poultry.
The biocidal activity of the compounds in question is moreover further intensified by the addition of copper in the form of a copper compound such as copper sulphate. The addition of an approximately equimolar quantity of copper is preferred, but smaller quantities of copper also already suffice to give a significant intensification of the activity.
The compounds according to formula I can form stabile complexes with copper. These copper complexes form part of the present invention too. These can be formed upon the addition of either Cu.sup.I salts or Cu.sup.II salts to the compounds.
The need for novel highly active biocidal compounds is great since in general the microorganisms to be combated, and the mycoplasms in particular, very rapidly develop a certain degree of resistance to the biocidal substances which have already been used for some time in infectious diseases caused by these microorganisms.
The compounds according to the invention can be prepared in the manner customary for such compounds.
The most generally usable method for the preparation of a compound I, wherein Y represents oxygen, consists in the reaction of a 4-amino-quinazoline or 4-amino-isoquinoline derivative of the formula II: ##STR3## or of a salt thereof, wherein R.sub.1, R.sub.2, R.sub.3 and X have the meaning given above, with a compound of the general formula III: ##STR4## or with an ester, acid halide or acid anhydride derived therefrom, wherein R.sub.4 has the meaning given above.
The starting compounds of the general formula II are in the majority of cases known. Where they are not previously known, they can be prepared in the manner known for similar compounds.
The most generally useful method for the preparation of compounds I, wherein Y represents the group NH, consists in the reaction of a 4-halo-quinazoline or isoquinoline compound of the formula IV: ##STR5## or of a salt thereof, wherein R.sub.1, R.sub.2, R.sub.3 and X have the meaning given above, Hal represents a halogen atom, with an amidine derivative according to the formula V: ##STR6##
This reaction is preferably carried out under basic reaction conditions.
Another method for the preparation of the compounds I, wherein Y represents an NH group, consists in the reaction of a compound of the general formula VI: ##STR7## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 have the meaning given above and Z represents a halogen, preferably chlorine, or an alkoxy(1-4C) group, with ammonia (NH.sub.3).
The last-mentioned method is particularly suitable for the synthesis of compounds I, wherein Y represents an NH group and R.sub.4 a substituted or unsubstituted phenyl group or hydrogen.
The starting compound according to the formula VI, wherein Z represents halogen, can inter alia be obtained by halogenating a corresponding compound of the general formula I, wherein Y represents oxygen. The compound VI where R.sub.4 is hydrogen and Z is OC.sub.2 H.sub.5 can be obtained by reacting a compound of the formula II with triethyl orthoformate.
Yet a further method for the preparation of compounds I, wherein Y represents an NH group, consists in the rea
REFERENCES:
patent: 3674791 (1972-07-01), Mathison
patent: 4125724 (1978-11-01), Howell
patent: 4282222 (1981-08-01), Bartmann et al.
Eur. J. Med. Chem. -Chim. Ther., 1984-19, No. 5, pp. 389-392, Synthesis and antimycoplasmal activity of 2,2'-bipyridyl analogues, Piet J. Pijper, Henk Van der Goot, Henk Timmerman and Wijbe Th. Nauta.
Linschoten, et al., "Chemical Abstracts.", vol. 101, 1985, Col. 101:110863v (abstract of Eur. J. Med. Chem, vol. 19, No. 2, 1984).
Timmerman Hendrik
van der Goot Henderikus
Akzo N.V.
Hollrah Glennon H.
Turnipseed James H.
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