OA11718A - Use of phosphonoformic acid derivatives for treating infections. - Google Patents

Claims (11)

1. -17-

   T*·» Patent Claims Use of a compound of the formula I O O

   Ru > p < Ri in which Rn is selected from the group which consists of C1-26 alkyl residues, C2-26alkenyl residues with 1 to 6 double bonds, C2-26 alkynyl residues with 1 to 6 triple bonds,Ci-26 acyl residues, Ar-Co-26-alkyl residues, C3-8-cycloalkyl-Co-26-alkyl residues, C3.8-heterocycloalkyl-Co-26-alkyl residues with one or two nitrogen, oxygen or sulfur atoms,halogen and OXn, wherein ail the above-stated residues may be substituted with C1.9alkyl, C1-9 alkoxy, hydroxy, amino, halogen or oxo groups, wherein Xn is selected from the group which consists of hydrogen, Cj.26 alkyl residues,C2-26 alkenyl residues with 1 to 6 double bonds, C2-26 alkynyl residues with 1 to 6 triplebonds, Ar-Co-26-alkyl residues, C3.8 cycloalkyl residues, C1.26 acyl residues, C3.8-heterocycloalkyl-Co-26-alkyl residues with one or two nitrogen, ôxygen or sulfur atoms,Ci-26 silyl residues, wherein ail the above-stated residues may be substituted with C1-9alkyl, C1-9 alkoxy, hydroxy, amino, halogen or oxo groups and consists of a cation of anorganic and inorganic base, in particular a métal of main groups I, Hor III of the periodicsystem, ammonium, substituted ammonium and ammonium compounds derived fromethylenediamine or amino acids, in which Ri and R2 are each independently selected from the group which consists of Ci.24 alkyl residues, C3.8 cycloalkyl residues, C3-8-cycloalkyl-Ci_24-alkyl residues, C1.24alkoxy residues, C1-24 alkylthio residues, Ci-24-alkoxy-Ci.24-alkyl residues and C1.24-alkylthio-Ci-24-alkyl residues, acyl residues, Ar-(Ci-24)-alkyl residues, C3.8-heterocycloalkyl-Co-24-alkyl residues, halogen and hydrogen, and each C1-24 alkyl residueand Ci-24 alkoxy residue may be branched or unbranched and be saturated or unsaturatedwith 2 to 6 double bonds and may optionally be substituted with hydroxy, amino,mercapto, halogen, oxo groups or Ci.24 alkoxy residues, C1-24 alkylcarbonyloxy residues,Ci-24 alkoxycarbonyloxy residues, C1.24 alkylthio residues, C1.24 alkylcarbonylthioresidues, C1.24 alkylamino residues, di-(Ci.24-alkyl)amino residues, C1.24 -18- alkylcarbonylamino residues, Ci.24-alkyl(Ci-24-alkylcarbonyl)amino residues, C1-24-alkoxycarbonylamino residues or Ci.24-alkyl-(Ci-24-alkoxycarbonyl)amino residues,wherein each aralkyl residue, heterocyclic residue, C1-24 alkyl residue and Ci-24 alkoxyresidue may be branched or unbranched and be saturated or unsaturated with 2 to 6double bonds or triple bonds, or in which R1-CH-CH-R2 fonns part of a C4.8 carbon ring, which may optionally besubstituted with hydroxy, mercapto, amino, halogen, oxo groups or with C1.24 alkylresidues, C1-24 alkoxy residues, C1.24 alkylthio residues, C1.24 alkylamino residues, di-(Ci-24-alkyl)aniino residues, C1-24 alkylcarbonyl residues, C1-24 alkylcarbonyloxy residues, Ci.24 alkoxycarbonyl residues, Ci-24 alkylcarbonylthio residues or C1.24 alkylcarbonylaminoresidues, Ci.24-alkyl-(Ci-24-alkylcarbonyl)amino residues, wherein each C1.24 alkylresidue may be branched or unbranched and be saturated or unsaturated with 1 to 6double bonds, or wherein Rio is a branched or unbranched Cm alkyl residue, and wherein R1-CH-CH-R2 forms part of the foranose or pyranose ring of a sugar, forexample D-ribose, D-arabinose, D-xylose, D-lyxose, D-glucose, D-galactose, D-mannose, D-talose, D-allose, D-altrose, D-gulose, D-idose or the corresponding Lisomers, wherein the hydroxy groups may each optionally be substituted by hydrogen,amino, azido, oxo, mercapto residues or C1.24 alkoxy residues, C1.24 alkylthio residues,Cj.24 alkylamino residues, di-(Ci-24-alkyl)amino residues, C1.24 alkylcarbonyloxyresidues, C1.24 alkylcarbonylthio residues, C1-24 alkylcarbonylamino residues, Ci-24-alkyl-(Ci-24-alkylcarbonyl)amino residues, wherein each C1-24 alkyl residue may be branched orunbranched and be saturated or unsaturated with 1 to 6 double bonds,and the pharmaceutically acceptable salts, esters and amides thereof and salts of the estersand the optical isomers thereof, for the prophylactic and therapeutic treatment of infectious processes in humans andanimais which are caused by bacteria, fungi or parasites and as a fongicide, bactéricide orherbicide in plants.
2. 2. Use according to claim 1, characterised in that Ri and R2 are each independently selectedfrom the group which consists of carboxyl residues, carboxamido residues, aryl residues,aryloxycarbonyl residues, aryl-Ci.24-alkyl residues, C1-24 alkoxycarbonyloxy residues, Ci.24 alkylaminocarbonyl residues, di-(Ci.24-alkyl)aminocarbonyl residues, aryl-Ci.24-alkoxycarbonyl residues, aryl-Ci-24-alkylaminocarbonyl residues, C1-24- alkylcarbonyloxy-(Ci.24)alkylmethoxycarbonyl residues, C1.24alkoxycarbonyloxymethoxycarbonyl residues, Ci-24-alkoxycarbonyloxy-(CM- 5 alkyl)methoxycarbonyl, wherein each Ci.24 alkyl residue may be branched or unbranchedand be saturated or unsaturated with 2 to 6 double bonds, and each Cm alkyl residue and

   -19- Ci-24 alkoxy residue may be branched or unbranched and be saturated or unsaturated, andeach aryl residue is of the formula II

   (II) wherein R3 and R4 are identical or different and are each selected from the group whichconsists of hydrogen, halogen, Cm alkyl residues, Cm alkoxy residues, formyl, acetyl,propionyl, butyryl residues, formyloxy, acetyloxy, propionyloxy, butyryloxy residues,Cm alkoxycarbonyl residues, ail of which may be branched or unbranched, or R3 and R4together form an unbranched saturated alkylene chain with 3 to 4 carbon atoms, which isattached to adjacent positions on the phenyl ring, or R3 and R4 together form amethylenedioxy residue, a 1,1-ethylidenedioxy residue, 1,1-ethenylenedioxy residue, a1,1-ethylenedioxy residue or a 1,2-ethylenedioxy residue, which are attached to adjacentpositions of the phenyl ring, or
3. 3. Use according to claim 1, wherein Ri and R2 are each independently selected from thegroup which consists of hydrogen groups, acetyl groups, formyl groups, hydroxy groupsand methyl groups, wherein the methyl group may optionally be substituted with ahydroxy group or mercapto group or with C1-24 alkoxy residues, C1.24 alkylcarbonyloxyresidues, C1.24 alkylthio residues or C1.24 alkylcarbonylthio residues, wherein the C1.24alkyl groups and C1.24 alkoxy groups may be branched or unbranched and be saturated orunsaturated with 1 to 6 double bonds.
4. 4. Use according to claim 3, wherein Ri is a methyl residue, which may optionally besubstituted with a hydroxy group or mercapto group or with C1.24 alkoxy residues, Ci-24alkylcarbonyloxy residues, C1.24 alkylthio residues or C1-24 alkylcarbonylthio residues,wherein the C1.24 alkyl groups and the C1.24 alkoxy groups may be branched orunbranched and be saturated or unsaturated with 1 to 6 double bonds, and R2 is ahydrogen residue.
5. .5. Use according to claim 1, wherein Ri and R2 are each independently selected from thegroup which consists of hydrogen and an n-octadecylmethyl residue. 117 18 10 15 20 25 30 -20-
6. 6. Use according to claim 5, wherein Ri is an n-octadecylmethyl residue and R2 a hydrogenresidue.
7. 7. Use according to claim 6, wherein the compound is in (R) configuration.
8. 8. Use according to one of the preceding daims for the treatment of infections caused bybacteria, fungi or uni- or multicellular parasites.
9. 9. Use according to claim 8 for the treatment of infections which are caused by bacteriawhich are selected from the group which consists of bacteria of the familyPropionibacteriaceae, in particular of the genus Propionibacterium, in particular thespecies Propionibacterium acnés, bacteria of the family Actinomycetaceae, in particularof the genus Actinomyces, bacteria of the genus Comynebacterium, in particular thespecies Corynebacterium diphtheriae and Corynebacterium pseudotuberculosis, bacteriaof the family Mycobacteriaceae, of the genus Mycobacterium, in particular the speciesMycobacterium leprae, Mycobacterium tuberculosis, Mycobacterium bovis andMycobacterium avium, bacteria of the family Chlamydiaceae, in particular the speciesChlamydia trachomatis and Chlamydia psittaci, bacteria of the genus Listeria, in .particular the species Listeria monocytogenes, bacteria of the species Erysipelthrixrhusiopathiae, bacteria of the genus Clostridium, bacteria of the genus Yersinia, thespecies Yersinia pestis, Yersinia pseudotuberculosis, Yersinia enterocolitica and Yersiniaruckeri, bacteria of the family Mycoplasmataceae, of the généra Mycoplasma andUreaplasma, in particular the species Mycoplasma pneumoniae, bacteria of the genusBrucella, bacteria of the genus Bordetella, bacteria of the family Neisseriaceae, inparticular of the généra Neisseria and Moraxella, in particular the species Neisseriameningitides, Neisseria gonorrhoeae and Moraxella bovis, bacteria of the familyVibrionaceae, in particular of the généra Vibrio, Aeromonas, Plesiomonas andPhotobacterium, in particular the species Vibrio cholerae, Vibrio anguillarum andAeromonas salmonicidas, bacteria of the genus Campylobacter, in particular the speciesCampylobacter jejuni, Campylobacter coli and Campylobacter fétus, bacteria of thegenus Hélicobacter, in particular the species Hélicobacter pylori, bacteria of the familiesSpirochaetaceae and Leptospiraceae, in particular of the généra Treponema, Borrelia andLeptospira, in particular Borrelia burgdorferi, bacteria of the genus Actinobacillus,bacteria of the family Legionellaceae, of the genus Légionella, bacteria of the familyRickettsiaceae and family Bartonellaceae, bacteria of the généra Nocardia andRhodococcus, bacteria of the genus Dermatophilus, bacteria of the familyPseudomonadaceae, in particular of the généra Pseudomonas and Xanthomonas, bacteriaof the family Enterobacteriaceae, in particular of the généra Escherichia, Klebsiella,Proteus, Providencia, Salmonella, Serratia and Shigella, bacteria of the family 35 -21 - 117 18 Pasteurellaceae, in particular of the genus Haemophilus, bacteria of the familyMicrococcaceae, in particular of the généra Micrococcus and Staphylococcus, bacteria ofthe family Streptococcaceae, in particular of the généra Streptococcus and Enterococcusand bacteria of the family Bacillaceae, in particular of the généra Bacillus andClostridium, and in the éradication of Hélicobacter in ulcers of the gastrointestinal tract.
10. 10. Use according to claim 8 for the prévention and treatment of infections caused byunicellular parasites which are selected from the group which consists of the causativeorganisme of malaria, sleeping sickness, Chagas’ disease, toxoplasmosis, amoebicdysentery, leishmaniases, trichomoniasis, pneumocystosis, balantidiasis, cryptosporidiosis, sarcocytosis, acanthamoebosis, naeglerosis, coccidiosis, giardiasis andlambliasis.
11. 11. Process for the treatment of infectious diseases caused by bacteria, fungi or parasites inwhich a therapeutically effective quantity of a compound according to one of daims 1 to7 is administered to a patient suffering from an infection caused by bacteria, fungi orparasites. 15