Derivatives of penicillanic acid
AssigneeLeo Pharmaceutical Products Ltd. A/S
InventorErnst T. Binderup
Life of this patent
Estimating the term…
Abstract
The present invention relates to new substituted 6.beta.-amidinopenicillanic acids; pharmaceuticallyacceptable salts, easily hydrolyzable esters thereof and salts of such esters; to methods of producing the compounds; to intermediates in their preparation, to pharmaceutical compositions containing the compounds; to dosage units thereof; and to their use.
Claims55
An antibiotic compound of the general formulae I, II, and III ##STR27## in which -A- stands for a straight or branched, saturated or unsaturated aliphatic hydrocarbon radical, having from 1 to 6 carbon atoms, which radical optionally can be substituted with an amino radical;
- R.sub.1 stands for hydrogen, or a lower alkyl radical having from 1 to 4 carbon atoms;
- R.sub.2 stands for hydrogen, a lower alkyl radical having from 1 to 4 carbon atoms, or a monacyl radical derived from a mono- or dibasic carboxylic acid, sulphuric acid, a sulphonic acid, a sulphinic acid, phosphoric acid, or a phosphonic acid, and R.sub.2 can represent an unsubstituted or a lower alkyl or phenyl substituted radical selected from the group consisting of carbamoyl, guanyl and guanylcarbamoyl radicals;
- R.sub.1 and R.sub.2 together with the nitrogen atom can form a monocyclic, saturated ring having from 4 to 8 carbon atoms;
- furthermore R.sub.1 and R.sub.2 together can represent a radical of the formula ##STR28## in which R.sub.3 and R.sub.4 each stands for hydrogen, lower alkyl, phenyl or phenyl-lower alkyl, or in which R.sub.3 and R.sub.4 together with the nitrogen atom form a monocyclic, saturated ring having from 4 to 7 carbon atoms;
- the groupings:
- ##STR29## represent saturated, monocyclic, bicyclic or spirocyclic ring systems, respectively, having from 4 to 11 carbon atoms in total;
- P stands for the penicillanic acid radical of the formula IV:
- ##STR30## and salts of the compounds of the formulae I, II, and III with pharmaceutically acceptable, non-toxic organic and inorganic acids or bases, and easily hydrolyzable pharmaceutically acceptable, non-toxic esters of the penicillanic acid derivatives of formulae I, II, and III.
An antibiotic compound of the general formula I ##STR31## in which -A- stands for a straight or branched, saturated or unsaturated aliphatic hydrocarbon radical, having from 1 to 6 carbon atoms, which radical optionally can be substituted with an amino radical;
- R.sub.1 stands for hydrogen, or a lower alkyl radical having from 1 to 4 carbon atoms;
- R.sub.2 stands for hydrogen, a lower alkyl radical having from 1 to 4 carbon atoms, or a monoacyl radical derived from a mono- or dibasic carboxylic acid, sulphuric acid, a sulphonic acid, a sulphinic acid, phosphoric acid, or a phosphonic acid, and R.sub.2 can represent an unsubstituted or a lower alkyl or phenyl substituted radical selected from the group consisting of carbamoyl, guanyl and guanylcarbamoyl radicals;
- R.sub.1 and R.sub.2 together with the nitrogen atom can form a monocyclic, saturated ring having from 4 to 8 carbon atoms;
- furthermore R.sub.1 and R.sub.2 together can represent a radical of the formula ##STR32## in which R.sub.3 and R.sub.4 each stands for hydrogen, lower alkyl, phenyl or phenyl-lower alkyl, or in which R.sub.3 and R.sub.4 together with the nitrogen ato form a monocyclic, saturated ring having from 4 to 7 carbon atoms;
- the grouping:
- ##STR33## represents a saturated monocyclic ring system having from 4 to 11 carbon atoms;
- P stands for the penicillanic acid radical of the formula IV:
- ##STR34## and salts of the compounds of the formula I with pharmaceutically acceptable, non-toxic organic and inorganic acids or bases, and easily hydrolyzable pharmaceutically acceptable, non-toxic esters of the penicillanic acid derivatives of formula I.
An antibiotic compound of the general formula II ##STR35## in which -A- stands for a straight or branched, saturated or unsaturated aliphatic hydrocarbon radical having from 1 to 6 carbon atoms, which radical optionally can be substituted with an amino radical;
- R.sub.1 stands for hydrogen, or a lower alkyl radical having from 1 to 4 carbon atoms;
- R.sub.2 stands for hydrogen, a lower alkyl radical having from 1 to 4 carbon atoms, or a monoacyl radical derived from a mono- or dibasic carboxylic acid, sulphuric acid, a sulphonic acid, a sulphinic acid, phosphoric acid, or a phosphonic acid, and R.sub.2 can represent an unsubstituted or a lower alkyl or phenyl substituted radical selected from the group consisting of carbamoyl, guanyl and guanylcarbamoyl radicals;
- R.sub.1 and R.sub.2 together with the nitrogen atom can form a monocyclic, saturated ring having from 4 to 8 carbon atoms;
- furthermore R.sub.1 and R.sub.2 together can represent a radical of the formula ##STR36## in which R.sub.3 and R.sub.4 each stands for hydrogen, lower alkyl, phenyl or phenyl-lower alkyl, or in which R.sub.3 and R.sub.4 together with the nitrogen atom form a monocyclic, saturated ring having from 4 to 7 carbon atoms;
- the grouping:
- ##STR37## represents a saturated, bicyclic ring system, having from 4 to 11 carbon atoms in total;
- P stands for the penicillanic acid radical of the formula ##STR38## and salts of the compounds of the formula II with pharmaceutically acceptable, non-toxic organic and inorganic acids or bases, and easily hydrolyzable pharmaceutically acceptable, non-toxic esters of the penicillanic acid derivatives of formula II.
An antibiotic compound of the general formula III ##STR39## in which -A- stands for a straight or branched, saturated or unsaturated aliphatic hydrocarbon radical, having from 1 to 6 carbon atoms, which radical optionally can be substituted from an amino radical;
- R.sub.1 stands for hydrogen, or a lower alkyl radical having from 1 to 4 carbon atoms;
- R.sub.2 stands for hydrogen, a lower alkyl radical having from 1 to 4 carbon atoms, or a monoacyl radical derived from a mono- or dibasic carboxylic acid, sulphuric acid, a sulphonic acid, a sulphinic acid, phosphoric acid, or a phosphonic acid, and R.sub.2 can represent an unsubstituted or a lower alkyl or phenyl substituted radical selected from the group consisting of carbamoyl, guanyl and guanylcarbamoyl radicals;
- R.sub.1 and R.sub.2 together with the nitrogen atom can form a monocyclic, saturated ring having 4 to 8 carbon atoms;
- furthermore R.sub.1 and R.sub.2 together can represent a radical of the formula ##STR40## in which R.sub.3 and R.sub.4 each stands for hydrogen, lower alkyl, phenyl or phenyl-lower alkyl, or in which R.sub.3 and R.sub.4 together with the nitrogen atom form a monocyclic, saturated ring having from 4 to 7 carbon atoms;
- the grouping:
- ##STR41## represents a saturated spirocyclic ring system having from 4 to 11 carbon atoms in total;
- P stands for the penicillanic acid radical of the formula ##STR42## and salts of the compounds of the formula III with pharmaceutically acceptable, non-toxic organic and inorganic acids or bases, and easily hydrolyzable pharmaceutically acceptable, non-toxic esters of the penicillanic acid derivatives of formula III.
6-[4'-aminomethyl-1'-piperidyl-methyleneamino]-penicillanic acid, and pharmaceutically acceptable, non-toxic salts and easily hydrolyzable esters thereof, and their salts.
6-[4'-(3"-aminopropyl)-1'-piperidyl-methyleneamino]-penicillanic acid, and pharmaceutically acceptable, non-toxic salts and easily hydrolyzable esters thereof, and their salts.
6-[4'-(2"-aminoethyl)-hexahydr o-1'H-azepin-1'-yl)-methyleneamino]-penicillanic acid, and pharmaceutically acceptable, non-toxic salts and easily hydrolyzable esters thereof, and their salts.
6-[4'-(3"-acetamidopropyl)-1'-piperidyl-methyleneamino]-penicillanic acid, and pharmaceutically acceptable, non-toxic salts and easily hydrolyzable esters thereof, and their salts.
6-[4'-(3"-(N,N-dimethylamino-methyleneamin o)-propyl)-1'-piperidyl-methyleneamino]-penicillanic acid, and pharmaceutically acceptable, non-toxic salts and easily hydrolyzable esters thereof, and their salts.
Bis-(6-[4'-(3"-aminopropyl)-1 '-piperidyl-methyleneamono]-penicillanoyloxy)-methane, and pharmaceutically acceptable, non-toxic salts thereof.
6-[(4'-(1",3"-diaminopropyl-2")-h exahydro-1'H-azepin-1'-yl)-methyleneamino]-penicillanic acid, and pharmaceutically acceptable, non-toxic salts and easily hydrolyzable esters thereof, and their salts.
6-[4'-(2"-aminoethyl)-1'-piperidyl-methyleneamino]-penicillanic acid, and pharmaceutically acceptable, non-toxic salts and easily hydrolyzable esters thereof, and their salts.
6-[4'-(3"-N,N-Dimethylaminopr opyl)-1'-piperidyl-methyleneamino]-penicillanic acid and pharmaceutically acceptable salts and easily hydrolyzable pharmaceutically acceptable esters thereof and their salts.
6-[4'-(2"-Aminobutyl)-1'-piperidyl-methyleneamino]-penicillanic acid and pharmaceutically acceptable salts and easily hydrolyzable pharmaceutically acceptable esters thereof and their salts.
An antibacterial composition in dosage unit form as claimed in claim 48 for oral treatment of patients containing from 0.05 g to 1.5 g of the active ingredient, calculated as the free acid.
Dependencies are inferred from the claim text.