DE19903398A1 - Use of thiadiazole derivatives for the prophylactic and therapeutic treatment of infections - Google Patents
Use of thiadiazole derivatives for the prophylactic and therapeutic treatment of infectionsInfo
- Publication number
- DE19903398A1 DE19903398A1 DE19903398A DE19903398A DE19903398A1 DE 19903398 A1 DE19903398 A1 DE 19903398A1 DE 19903398 A DE19903398 A DE 19903398A DE 19903398 A DE19903398 A DE 19903398A DE 19903398 A1 DE19903398 A1 DE 19903398A1
- Authority
- DE
- Germany
- Prior art keywords
- viruses
- genus
- bacteria
- virus
- family
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 208000015181 infectious disease Diseases 0.000 title claims abstract description 13
- 150000004867 thiadiazoles Chemical class 0.000 title claims abstract description 11
- 238000011282 treatment Methods 0.000 title claims description 13
- 230000001225 therapeutic effect Effects 0.000 title abstract description 3
- 230000000069 prophylactic effect Effects 0.000 title 1
- 241000894006 Bacteria Species 0.000 claims abstract description 61
- 241000700605 Viruses Species 0.000 claims abstract description 57
- 241001465754 Metazoa Species 0.000 claims abstract description 26
- 244000045947 parasite Species 0.000 claims abstract description 11
- 241000233866 Fungi Species 0.000 claims abstract description 8
- -1 alkyl radicals Chemical class 0.000 claims description 122
- 241000282412 Homo Species 0.000 claims description 19
- 239000004480 active ingredient Substances 0.000 claims description 17
- 230000008029 eradication Effects 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 150000002367 halogens Chemical class 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 9
- 238000002560 therapeutic procedure Methods 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 claims description 8
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 claims description 8
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 claims description 8
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 7
- SGKRLCUYIXIAHR-AKNGSSGZSA-N (4s,4ar,5s,5ar,6r,12ar)-4-(dimethylamino)-1,5,10,11,12a-pentahydroxy-6-methyl-3,12-dioxo-4a,5,5a,6-tetrahydro-4h-tetracene-2-carboxamide Chemical compound C1=CC=C2[C@H](C)[C@@H]([C@H](O)[C@@H]3[C@](C(O)=C(C(N)=O)C(=O)[C@H]3N(C)C)(O)C3=O)C3=C(O)C2=C1O SGKRLCUYIXIAHR-AKNGSSGZSA-N 0.000 claims description 6
- 239000004098 Tetracycline Substances 0.000 claims description 6
- AEUTYOVWOVBAKS-UWVGGRQHSA-N ethambutol Chemical compound CC[C@@H](CO)NCCN[C@@H](CC)CO AEUTYOVWOVBAKS-UWVGGRQHSA-N 0.000 claims description 6
- 208000006454 hepatitis Diseases 0.000 claims description 6
- 231100000283 hepatitis Toxicity 0.000 claims description 6
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- 229940124530 sulfonamide Drugs 0.000 claims description 6
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- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
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- XEEQGYMUWCZPDN-DOMZBBRYSA-N (-)-(11S,2'R)-erythro-mefloquine Chemical compound C([C@@H]1[C@@H](O)C=2C3=CC=CC(=C3N=C(C=2)C(F)(F)F)C(F)(F)F)CCCN1 XEEQGYMUWCZPDN-DOMZBBRYSA-N 0.000 claims description 4
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 claims description 4
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 235000001258 Cinchona calisaya Nutrition 0.000 claims description 4
- HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims description 4
- 241000193403 Clostridium Species 0.000 claims description 4
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- 241000709687 Coxsackievirus Species 0.000 claims description 4
- 241000709661 Enterovirus Species 0.000 claims description 4
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 claims description 4
- 241000589989 Helicobacter Species 0.000 claims description 4
- 241000700721 Hepatitis B virus Species 0.000 claims description 4
- 241000724675 Hepatitis E virus Species 0.000 claims description 4
- 208000007514 Herpes zoster Diseases 0.000 claims description 4
- 241000588653 Neisseria Species 0.000 claims description 4
- 241001631646 Papillomaviridae Species 0.000 claims description 4
- 235000010678 Paulownia tomentosa Nutrition 0.000 claims description 4
- PJSFRIWCGOHTNF-UHFFFAOYSA-N Sulphormetoxin Chemical compound COC1=NC=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1OC PJSFRIWCGOHTNF-UHFFFAOYSA-N 0.000 claims description 4
- DZBUGLKDJFMEHC-UHFFFAOYSA-N acridine Chemical compound C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 claims description 4
- 229960004191 artemisinin Drugs 0.000 claims description 4
- BLUAFEHZUWYNDE-NNWCWBAJSA-N artemisinin Chemical compound C([C@](OO1)(C)O2)C[C@H]3[C@H](C)CC[C@@H]4[C@@]31[C@@H]2OC(=O)[C@@H]4C BLUAFEHZUWYNDE-NNWCWBAJSA-N 0.000 claims description 4
- 229930101531 artemisinin Natural products 0.000 claims description 4
- JFIOVJDNOJYLKP-UHFFFAOYSA-N bithionol Chemical compound OC1=C(Cl)C=C(Cl)C=C1SC1=CC(Cl)=CC(Cl)=C1O JFIOVJDNOJYLKP-UHFFFAOYSA-N 0.000 claims description 4
- 229960002326 bithionol Drugs 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- WZOZEZRFJCJXNZ-ZBFHGGJFSA-N cefoxitin Chemical group N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)CC1=CC=CS1 WZOZEZRFJCJXNZ-ZBFHGGJFSA-N 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 229960003677 chloroquine Drugs 0.000 claims description 4
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 claims description 4
- 229960003405 ciprofloxacin Drugs 0.000 claims description 4
- 229960003324 clavulanic acid Drugs 0.000 claims description 4
- HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 claims description 4
- 229960002227 clindamycin Drugs 0.000 claims description 4
- KDLRVYVGXIQJDK-AWPVFWJPSA-N clindamycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@H](C)Cl)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 KDLRVYVGXIQJDK-AWPVFWJPSA-N 0.000 claims description 4
- 210000001035 gastrointestinal tract Anatomy 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 201000004792 malaria Diseases 0.000 claims description 4
- 229960001962 mefloquine Drugs 0.000 claims description 4
- 229960000282 metronidazole Drugs 0.000 claims description 4
- VAOCPAMSLUNLGC-UHFFFAOYSA-N metronidazole Chemical compound CC1=NC=C([N+]([O-])=O)N1CCO VAOCPAMSLUNLGC-UHFFFAOYSA-N 0.000 claims description 4
- RJMUSRYZPJIFPJ-UHFFFAOYSA-N niclosamide Chemical compound OC1=CC=C(Cl)C=C1C(=O)NC1=CC=C([N+]([O-])=O)C=C1Cl RJMUSRYZPJIFPJ-UHFFFAOYSA-N 0.000 claims description 4
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- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 claims description 4
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- 229940056360 penicillin g Drugs 0.000 claims description 4
- ZJAOAACCNHFJAH-UHFFFAOYSA-N phosphonoformic acid Chemical compound OC(=O)P(O)(O)=O ZJAOAACCNHFJAH-UHFFFAOYSA-N 0.000 claims description 4
- 229960002292 piperacillin Drugs 0.000 claims description 4
- 230000002265 prevention Effects 0.000 claims description 4
- 229960005385 proguanil Drugs 0.000 claims description 4
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- 229960005134 pyrantel Drugs 0.000 claims description 4
- YSAUAVHXTIETRK-AATRIKPKSA-N pyrantel Chemical compound CN1CCCN=C1\C=C\C1=CC=CS1 YSAUAVHXTIETRK-AATRIKPKSA-N 0.000 claims description 4
- 229960000611 pyrimethamine Drugs 0.000 claims description 4
- WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 claims description 4
- 229960000948 quinine Drugs 0.000 claims description 4
- 229960004673 sulfadoxine Drugs 0.000 claims description 4
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- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 claims description 4
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- SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 1
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- 231100000844 hepatocellular carcinoma Toxicity 0.000 description 1
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- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 239000012678 infectious agent Substances 0.000 description 1
- 201000006747 infectious mononucleosis Diseases 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000005929 isobutyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])OC(*)=O 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
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- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 206010023332 keratitis Diseases 0.000 description 1
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- 235000010355 mannitol Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000001525 mentha piperita l. herb oil Substances 0.000 description 1
- 208000010453 mesenteric lymphadenitis Diseases 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 229960001952 metrifonate Drugs 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
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- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- CQDGTJPVBWZJAZ-UHFFFAOYSA-N monoethyl carbonate Chemical compound CCOC(O)=O CQDGTJPVBWZJAZ-UHFFFAOYSA-N 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 208000027531 mycobacterial infectious disease Diseases 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000003605 opacifier Substances 0.000 description 1
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- 125000003431 oxalo group Chemical group 0.000 description 1
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- 238000007911 parenteral administration Methods 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 235000019477 peppermint oil Nutrition 0.000 description 1
- 208000008494 pericarditis Diseases 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 125000006678 phenoxycarbonyl group Chemical group 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 229960005141 piperazine Drugs 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- MISVBCMQSJUHMH-UHFFFAOYSA-N pyrimidine-4,6-diamine Chemical class NC1=CC(N)=NC=N1 MISVBCMQSJUHMH-UHFFFAOYSA-N 0.000 description 1
- 229960001404 quinidine Drugs 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 210000000697 sensory organ Anatomy 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 210000000952 spleen Anatomy 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 208000006379 syphilis Diseases 0.000 description 1
- 229960002722 terbinafine Drugs 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229940040944 tetracyclines Drugs 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- NLVFBUXFDBBNBW-PBSUHMDJSA-S tobramycin(5+) Chemical compound [NH3+][C@@H]1C[C@H](O)[C@@H](C[NH3+])O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H]([NH3+])[C@H](O)[C@@H](CO)O2)O)[C@H]([NH3+])C[C@@H]1[NH3+] NLVFBUXFDBBNBW-PBSUHMDJSA-S 0.000 description 1
- 229960004880 tolnaftate Drugs 0.000 description 1
- FUSNMLFNXJSCDI-UHFFFAOYSA-N tolnaftate Chemical compound C=1C=C2C=CC=CC2=CC=1OC(=S)N(C)C1=CC=CC(C)=C1 FUSNMLFNXJSCDI-UHFFFAOYSA-N 0.000 description 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- NFACJZMKEDPNKN-UHFFFAOYSA-N trichlorfon Chemical compound COP(=O)(OC)C(O)C(Cl)(Cl)Cl NFACJZMKEDPNKN-UHFFFAOYSA-N 0.000 description 1
- 241000712461 unidentified influenza virus Species 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-O vancomycin(1+) Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C([O-])=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)[NH2+]C)[C@H]1C[C@](C)([NH3+])[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-O 0.000 description 1
- 235000019871 vegetable fat Nutrition 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 208000012498 virus associated tumor Diseases 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 125000005023 xylyl group Chemical group 0.000 description 1
- 239000011787 zinc oxide Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/433—Thidiazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Epidemiology (AREA)
- Tropical Medicine & Parasitology (AREA)
- Virology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Die Erfindung betrifft die Verwendung von Thiadiazolderivaten zur therapeutischen und prophylaktischen Behandlung von Infek tionen bei Mensch und Tier, die durch Viren, Bakterien, Pilze und Parasiten hervorgerufen werden.The invention relates to the use of thiadiazole derivatives for the therapeutic and prophylactic treatment of infections in humans and animals caused by viruses, bacteria, fungi and parasites are caused.
Es besteht ein starker Bedarf, für die Bereicherung der Be handlung von Mensch und Tier sowie den Schutz von Pflanzen Mittel bereitzustellen, die eine starke Wirksamkeit gegen In fektionen besitzen.There is a strong need to enrich the Be action of humans and animals as well as the protection of plants To provide agents that are highly effective against In own fections.
Aufgabe der vorliegenden Erfindung ist es daher, eine Substanz bereitzustellen, die bei Infektionen durch Viren, Bakterien, Pilze und Parasiten bei Menschen und. Tieren einsetzbar ist.The object of the present invention is therefore a substance to provide, in the case of infections caused by viruses, bacteria, Fungi and parasites in humans and. Animals can be used.
Diese Aufgabe wird in völlig überraschender Weise durch die Verwendung der in Anspruch 1 definierte Stoffgruppe gelöst. Diese Stoffgruppe zeigt eine antiinfektiöse Wirkung gegen Vi ren, bestimmte Bakterien, Pilze, ein- und mehrzellige Parasi ten.This task is done in a completely surprising way by Use of the group of substances defined in claim 1 solved. This group of substances shows an anti-infectious effect against Vi certain bacteria, fungi, single and multicellular parasites ten.
Die erfindungsgemäß verwendeten Thiadiazolderivate entsprechen
der allgemeinen Formel (I):
The thiadiazole derivatives used according to the invention correspond to the general formula (I):
in der n eine ganze Zahl von 0 bis 4 ist,
und
in der R1, R2, R3, R4, R5 und R6 gleich oder verschieden sind und
aus der Gruppe ausgewählt sind, die aus Wasserstoff, substitu
ierten und unsubstituierten Alkylresten, substituierten und
unsubstituierten Alkoxyresten, substituierten und unsubstitu
ierten Acylresten, substituierten oder unsubstituierten Cy
cloalkyl-(C0-26)-alkylresten, substituierten und unsubstituier
ten Cycloalkyl-(C0-26)-alkoxyresten und Halogen besteht, wobei
jeder Alkylrest, jeder Alkoxyrest und jeder Acylrest verzweigt
oder unverzweigt und jeder Alkylrest, jeder Acylrest, jeder
Alkoxyrest und jede Cyclo-(C0-26)-alkylgruppe gesättigt oder mit
ein oder mehreren Doppel- oder Dreifachbindungen ungesättigt
sein kann und ein oder zwei Kohlenstoffatome der Cycloalkyl
gruppen durch Stickstoff-, Sauerstoff- oder Schwefelatome er
setzt sein können.in which n is an integer from 0 to 4,
and
in which R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are identical or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted alkoxy radicals, substituted and unsubstituted acyl radicals , substituted or unsubstituted cycloalkyl (C 0-26 ) alkyl radicals, substituted and unsubstituted cycloalkyl (C 0-26 ) alkoxy radicals and halogen, where each alkyl radical, each alkoxy radical and each acyl radical is branched or unbranched and each alkyl radical, each acyl radical, each alkoxy radical and each cyclo (C 0-26 ) alkyl group can be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl groups can be replaced by nitrogen, oxygen or sulfur atoms .
Bevorzugt steht R1 für COOC2H5.R 1 is preferably COOC 2 H 5 .
Bevorzugt sind ferner Verbindungen, in denen R2 bis R6 aus der Gruppe ausgewählt sind, die aus Wasserstoff und Halogen, ins besondere Chlor, besteht.Also preferred are compounds in which R 2 to R 6 are selected from the group consisting of hydrogen and halogen, especially chlorine.
Bevorzugt steht n außerdem für 1 oder 2. N is also preferably 1 or 2.
Besonderheiten der obigen Definitionen und geeignete Beispiele
dafür werden nachfolgend angegeben:
"Acyl"' ist ein Substituent, der von einer Säure stammt, wie
von einer organischen Carbonsäure, Kohlensäure, Carbaminsäure
oder der den einzelnen vorstehenden Säuren entsprechenden
Thiosäure oder Imidsäure, oder von einer organischen Sulfon
säure, wobei diese Säuren jeweils aliphatische, aromatische
und/oder heterocyclische Gruppen im Molekül umfassen sowie
Carbamoyl oder Carbamimidoyl.Special features of the above definitions and suitable examples are given below:
"Acyl"'is a substituent derived from an acid, such as from an organic carboxylic acid, carbonic acid, carbamic acid or the thioic acid or imidic acid corresponding to the individual above acids, or from an organic sulfonic acid, these acids each being aliphatic, aromatic and / or heterocyclic groups in the molecule as well as carbamoyl or carbamimidoyl.
Geeignete Beispiele für diese Acylgruppen werden nachfolgend angegeben.Suitable examples of these acyl groups are shown below specified.
Als aliphatische Acylgruppen werden von einer aliphatischen
Säure stammende Acylreste bezeichnet, zu denen die folgenden
gehören:
Alkanoyl (z. B. Formyl, Acetyl, Propionyl, Butyryl, Isobutyryl,
Valeryl, Isovaleryl, Pivaloyl etc.);
Alkenoyl (z. B. Acryloyl, Methacryloyl, Crotonoyl etc.);
Alkylthioalkanoyl (z. B. Methylthioacetyl, Ethylthioacetyl
etc.)
Alkansulfonyl (z. B. Mesyl, Ethansulfonyl, Propansulfonyl
etc.);
Alkoxycarbonyl (z. B. Methoxycarbonyl, Ethoxycarbonyl, Propoxy
carbonyl, Isopropoxycarbonyl, Butoxycarbonyl, Isobutoxycar
bonyl etc.);
Alkylcarbamoyl (z. B. Methylcarbamoyl etc.);
(N-Alkyl)-thiocarbamoyl (z. B. (N-Methyl)-thiocarbamoyl etc.);
Alkylcarbamimidoyl (z. B. Methylcarbamimidoyl etc.);
Oxalo;
Alkoxalyl (z. B. Methoxalyl, Ethoxalyl, Propoxalyl etc.).Aliphatic acyl groups are acyl radicals derived from an aliphatic acid, which include the following:
Alkanoyl (e.g. formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl etc.);
Alkenoyl (e.g. acryloyl, methacryloyl, crotonoyl etc.);
Alkylthioalkanoyl (e.g. methylthioacetyl, ethylthioacetyl etc.)
Alkanesulfonyl (e.g. mesyl, ethanesulfonyl, propanesulfonyl, etc.);
Alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxy carbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, etc.);
Alkyl carbamoyl (e.g. methyl carbamoyl etc.);
(N-alkyl) thiocarbamoyl (e.g. (N-methyl) thiocarbamoyl etc.);
Alkyl carbamimidoyl (e.g. methyl carbamimidoyl etc.);
Oxalo;
Alkoxalyl (e.g. methoxalyl, ethoxalyl, propoxalyl etc.).
Bei den obigen Beispielen für aliphatische Acylgruppen kann der aliphatische Kohlenwasserstoffteil, insbesondere die Al kylgruppe bzw. der Alkanrest, ggf. einen oder mehrere geeigne te Substituenten aufweisen, wie Amino, Halogen (z. B. Fluor, Chlor, Brom etc..), Hydroxy, Hydroxyimino, Carboxy, Alkoxy (z. B. Methoxy, Ethoxy, Propoxy etc.), Alkoxycarbonyl, Acylami no (z. B. Benzyloxycarbonylamino etc.), Acyloxy (z. B. Acetoxy, Benzoyloxy etc.) und dergleichen; als bevorzugte aliphatische Acylreste mit solchen Substituenten sind z. B. mit Amino, Car boxy, Amino und Carboxy, Halogen, Acylamino oder dergleichen substituierte Alkanoyle zu nennen.In the above examples of aliphatic acyl groups the aliphatic hydrocarbon part, especially the Al kylgruppe or the alkane radical, optionally one or more suitable have substituents such as amino, halogen (e.g. fluorine, Chlorine, bromine etc.), hydroxy, hydroxyimino, carboxy, alkoxy (e.g. methoxy, ethoxy, propoxy etc.), alkoxycarbonyl, acylami no (e.g. benzyloxycarbonylamino etc.), acyloxy (e.g. acetoxy, Benzoyloxy etc.) and the like; as the preferred aliphatic Acyl radicals with such substituents are e.g. B. with amino, car boxy, amino and carboxy, halogen, acylamino or the like to name substituted alkanoyle.
Als aromatische Acylreste werden solche Acylreste bezeichnet,
die von einer Säure mit substituierter oder nicht substituier
ter Arylgruppe stammen, wobei die Arylgruppe Phenyl, Toluyl,
Xylyl, Naphthyl und dergleichen umfassen kann; geeignete Bei
spiele werden nachfolgend angegeben:
Aroyl (z. B. Benzoyl, Toluoyl, Xyloyl, Naphthoyl, Phthaloyl
etc.);
Aralkanoyl (z. B. Phenylacetyl etc.);
Aralkenoyl (z. B. Cinnamoyl etc.);
Aryloxyalkanoyl (z. B. Phenoxyacetyl etc.);
Arylthioalkanoyl (z. B. Phenylthioacetyl etc.);
Arylaminoalkanoyl (z. B. N-Phenylglycyl, etc.);
Arensulfonyl (z. B. Benzolsulfonyl, Tosyl bzw. Toluolsulfonyl,
Naphthalinsulfonyl etc.);
Aryloxycarbonyl (z. B. Phenoxycarbonyl, Naphthyl-oxycarbonyl
etc.);
Aralkoxycarbonyl (z. B. Benzyloxycarbonyl etc.);
Arylcarbamoyl (z. B. Phenylcarbamoyl, Naphthylcarbamoyl etc.);
Arylglyoxyloyl (z. B. Phenylglyoxyloyl etc.).Aromatic acyl radicals are those acyl radicals which derive from an acid having a substituted or unsubstituted aryl group, where the aryl group can include phenyl, toluyl, xylyl, naphthyl and the like; Suitable examples are given below:
Aroyl (e.g. benzoyl, toluoyl, xyloyl, naphthoyl, phthaloyl etc.);
Aralkanoyl (e.g. phenylacetyl etc.);
Aralkenoyl (e.g. cinnamoyl etc.);
Aryloxyalkanoyl (e.g. phenoxyacetyl etc.);
Arylthioalkanoyl (e.g. phenylthioacetyl etc.);
Arylaminoalkanoyl (e.g. N-phenylglycyl, etc.);
Arenesulfonyl (e.g. benzenesulfonyl, tosyl or toluenesulfonyl, naphthalenesulfonyl, etc.);
Aryloxycarbonyl (e.g. phenoxycarbonyl, naphthyloxycarbonyl etc.);
Aralkoxycarbonyl (e.g. benzyloxycarbonyl etc.);
Arylcarbamoyl (e.g. phenylcarbamoyl, naphthylcarbamoyl etc.);
Arylglyoxyloyl (e.g. phenylglyoxyloyl etc.).
Bei den vorstehenden Beispielen für aromatische Acylreste kann
der aromatische Kohlenwasserstoffteil (insbesondere der Aryl
rest) und/oder der aliphatische Kohlenwasserstoffteil (insbe
sondere der Alkanrest) ggf. ein oder mehrere geeignete Substi
tuenten aufweisen, wie solche, die als geeignete Substituenten
für die Alkylgruppe bzw. den Alkanrest angegeben werden. Ins
besondere und als Beispiel für bevorzugte aromatische Acylre
ste mit besonderen Substituenten werden mit Halogen und Hy
droxy oder mit Halogen und Acyloxy substituiertes Arvyl und
mit Hydroxy, Hydroxyimino, Dihalogenalkanoyloxyimino substitu
iertes Aralkanoyl angegeben sowie
Arylthiocarbamoyl (z. B. Phenylthiocarbamoyl etc.);
Arylcarbamimidoyl (z. B. Phenylcarbamimidoyl etc.).In the above examples of aromatic acyl radicals, the aromatic hydrocarbon part (in particular the aryl radical) and / or the aliphatic hydrocarbon part (in particular the alkane radical) can optionally have one or more suitable substituents, such as those which are suitable substituents for the alkyl group or the alkane radical can be given. In particular, and as an example of preferred aromatic acyl radicals with special substituents, arvyl substituted with halogen and hydroxy or with halogen and acyloxy and aralkanoyl substituted with hydroxy, hydroxyimino, dihalogenalkanoyloxyimino are also indicated
Arylthiocarbamoyl (e.g. phenylthiocarbamoyl etc.);
Arylcarbamimidoyl (e.g. phenylcarbamimidoyl etc.).
Als heterocyclischer Acylrest wird ein Acylrest verstanden,
der von einer Säure mit heterocyclischer Gruppe stammt; dazu
gehören:
Heterocyclisches Carbonyl, bei dem der heterocyclische Rest
ein aromatischer oder aliphatischer 5- bis 6-gliedriger He
terocyclus mit zumindest einem Heteroatom aus der Gruppe
Stickstoff, Sauerstoff und Schwefel ist (z. B. Thiophenyl, Fu
royl, Pyrrolcarbonyl, Nicotinoyl etc.);
Heterocyclus-Alkanoyl, bei dem der heterocyclische Rest 5- bis
6-gliedrig ist und zumindest ein Heteroatom aus der Gruppe
Stickstoff, Sauerstoff und Schwefel aufweist (z. B. Thiophen
yl-acetyl, Furylacetyl, Imidazolylpropionyl, Tetrazolylacetyl,
2-(2-Amino-4-thiazolyl)-2-methoxyiminoacetyl etc.) und der
gleichen.A heterocyclic acyl radical is understood to mean an acyl radical which comes from an acid with a heterocyclic group; this includes:
Heterocyclic carbonyl, in which the heterocyclic radical is an aromatic or aliphatic 5- to 6-membered heterocycle with at least one heteroatom from the group consisting of nitrogen, oxygen and sulfur (e.g. thiophenyl, fuoyl, pyrrole carbonyl, nicotinoyl etc.);
Heterocycle alkanoyl, in which the heterocyclic radical is 5- to 6-membered and has at least one heteroatom from the group consisting of nitrogen, oxygen and sulfur (e.g. thiophene yl-acetyl, furylacetyl, imidazolylpropionyl, tetrazolylacetyl, 2- (2- Amino-4-thiazolyl) -2-methoxyiminoacetyl etc.) and the like.
Bei den obigen Beispielen für heterocyclische Acylreste kann der Heterocyclus und/oder der aliphatische Kohlenwasserstoff teil ggf. einen oder mehrere geeignete Substituenten aufwei sen, wie die gleichen, die als geeignet für Alkyl- und Alkan gruppen angegeben werden.In the above examples of heterocyclic acyl residues the heterocycle and / or the aliphatic hydrocarbon some may have one or more suitable substituents sen, like the same ones that are suitable for alkyl and alkane groups can be specified.
"Alkyl" ist, soweit nicht anders definiert, ein gerad- oder verzweigtkettiger Alkylrest mit bis zu 26 Kohlenstoffatomen, wie Methyl, Ethyl, Propyl, Isopropyl, Butyl, Isobutyl, tert.- Butyl, Pentyl, Hexyl und dergleichen. Er kann z. B. mit Hydro xy-, Amino-, Halogen- (z. B. Fluor, Brom, Chlor), Oxoresten und Alkoxyresten, wie Methoxy-, Ethoxyresten, substituiert sein.Unless otherwise defined, "alkyl" is a straight or branched chain alkyl radical with up to 26 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert.- Butyl, pentyl, hexyl and the like. He can e.g. B. with hydro xy, amino, halogen (e.g. fluorine, bromine, chlorine), oxo residues and Alkoxy radicals, such as methoxy, ethoxy radicals, may be substituted.
"Alkoxyrest" ist, soweit nicht anders definiert, ein gerad- oder verzweigtkettiger Alkoxyrest mit bis zu 26 Kohlenstoffa tomen, wie ein Methoxy, Ethoxyreste, etc.. Er kann z. B. mit Hydroxy-, Amino-, Halogen-, Oxogruppen und Alkoxyresten, wie Methoxy-, Ethoxyresten, substituiert sein.Unless otherwise defined, "alkoxy radical" is a straight or branched chain alkoxy with up to 26 carbon a toms, such as a methoxy, ethoxy radicals, etc. He can z. B. with Hydroxy, amino, halogen, oxo groups and alkoxy radicals, such as Methoxy, ethoxy, may be substituted.
"Cycloalkyl-(C0-26)-alkylreste" bzw. sind cyclische Verbindun gen mit 3 bis 8 Kohlenstoffatome, die direkt oder über einen Alkylenrest an das Grundgerüst gebunden sind. Der Alkylenrest kann verzweigt, unverzweigt und gesättigt oder mit Doppelbin dungen ungesättigt sein. Mögliche Substituenten des Cycloal kylrestes sind u. a. Alkoxyreste, Alkylreste, Hydroxyreste, Ha logenreste, Aminoreste, Oxoreste. Die Cycloalkylgruppen können mit der entsprechenden Anzahl an Doppelbindungen auch aroma tisch sein, d. h. Aryl-(C0-26)-alkylreste (z. B. Phenyl-, Pyridyl-, Naphthyl- etc.) sein. Insbesondere die aromatischen cy clischen Verbindungen können ferner Substituenten, wie Nitro gruppen und CF3 und Phenylreste, enthalten."Cycloalkyl- (C 0-26 ) alkyl radicals" or are cyclic compounds with 3 to 8 carbon atoms, which are bonded directly or via an alkylene radical to the backbone. The alkylene radical can be branched, unbranched and saturated or unsaturated with double bonds. Possible substituents of the cycloal kylrestes include alkoxy residues, alkyl residues, hydroxy residues, halogen residues, amino residues, oxo residues. The cycloalkyl groups can also be aromatic with the corresponding number of double bonds, ie aryl (C 0-26 ) alkyl radicals (for example phenyl, pyridyl, naphthyl, etc.). In particular, the aromatic cyclic compounds can also contain substituents, such as nitro groups and CF 3 and phenyl radicals.
"Cycloalkyl-(C0-26)-alkoxyreste" sind entsprechend den obigen "Cycloalkyl-(C0-26)-alkylresten" definiert. Bei den Cycloalkyl- (C0-26)-alkoxyresten ist die Cycloalkylgruppe über ein Sauer stoff oder eine Alkoxygruppe an das Grundgerüst gebunden."Cycloalkyl (C 0-26 ) alkoxy radicals" are defined in accordance with the above "cycloalkyl (C 0-26 ) alkyl radicals". In the cycloalkyl (C 0-26 ) alkoxy radicals, the cycloalkyl group is bonded to the basic structure via an oxygen or an alkoxy group.
Die erfindungsgemäß verwendeten Verbindungen der Formel (I) lassen beispielsweise für Doppelbindungen enthaltende oder chirale Gruppen R1 bis R6 das Auftreten räumlicher Isomerer zu. Die erfindungsgemäße Verwendung der Verbindungen umfaßt alle räumlichen Isomere sowohl als Reinstoffe als auch in Form ih rer Mischungen.The compounds of the formula (I) used according to the invention allow, for example for double-containing or chiral groups R 1 to R 6, the occurrence of spatial isomers. The use of the compounds according to the invention includes all spatial isomers both as pure substances and in the form of their mixtures.
Die Thiadiazolderivate sind insbesondere für die therapeuti sche und prophylaktischen Behandlung von Infektionen bei Mensch und Tier geeignet, die durch Viren, Bakterien, ein- und mehrzellige Parasiten und Pilze hervorgerufen werden.The thiadiazole derivatives are especially for the therapeuti and prophylactic treatment of infections Suitable for humans and animals, caused by viruses, bacteria, and multicellular parasites and fungi are caused.
Die beschriebenen Verbindungen, d. h. die Thiadiazolderivate nach der Formel (I) zeigen eine starke zytotoxische Wirksam keit gegenüber ein- und mehrzelligen Parasiten. Die Verbindun gen sind gegen einzellige Parasiten (d. h. Protozoen) wirksam, insbesondere gegen Erreger der Malaria und der Schlafkrankheit sowie der Chagas-Krankheit, der Toxoplasmose, der Amöbenruhr, der Leishmaniosen, der Trichomoniasis, der Pneumozystose, der Balantidiose, der Kryptosporidiose, der Sarkozystose, der Akanthamöbose, der Naeglerose, der Kokzidiose, der Giardiose und der Lambliose.The compounds described, i. H. the thiadiazole derivatives according to formula (I) show a strong cytotoxic effect against single and multicellular parasites. The connection genes are effective against unicellular parasites (i.e. protozoa), especially against pathogens of malaria and sleeping sickness as well as Chagas disease, toxoplasmosis, amoebic dysentery, leishmaniasis, trichomoniasis, pneumocystosis, the Balantidiosis, Cryptosporidiosis, Sarcocystosis, The Akanthamöbose, Naeglerose, Coccidiosis, Giardiosis and the lambliosis.
Sie sind daher insbesondere als Malariaprophylaxe und als Pro
phylaxe der Schlafkrankheit sowie der Chagas-Krankheit, der
Toxoplasmose, der Amöbenruhr, der Leishmaniosen, der Trichomo
niasis, der Pneumozystose, der Balantidiose, der Kryptospori
diose, der Sarkozystose, der Akanthamöbose, der Naeglerose,
der Kokzidiose, der Giardiose und der Lambliose geeignet.
Die erfindungsgemäßen Wirkstoffe sind insbesondere gegen die
folgenden Bakterien einsetzbar:
Bakterien der Familie Propionibacteriaceae, insbesondere der
Gattung Propionibacterium, insbesondere die Art Propionibacte
rium acnes,
Bakterien der Familie Actinomycetaceae, insbesondere der Gat
tung Actinomyces,
Bakterien der Gattung Corynebacterium, insbesondere die Arten
Corynebacterium diphteriae und Corynebacterium pseudotubercu
losis,
Bakterien der Familie Mycobacteriaceae, der Gattung Mycobacte
rium, insbesondere die Arten Mycobacterium leprae, Mycobacte
rium tuberculosis, Mycobacterium bovis und Mycobacterium avi
um,
Bakterien der Familie Chlamydiaceae, insbesondere die Spezies
Chlamydia trachomatis und Chlamydia psittaci,
Bakterien der Gattung Listeria, insbesondere die Art Listeria
monocytogenes,
Bakterien der Art Erysipelthrix rhusiopathiae,
Bakterien der Gattung Clostridium,
Bakterien der Gattung Yersinia, der Spezies Yersinia pestis,
Yersinia pseudotuberculosis, Yersinia enterocolitica und Yer
sinia ruckeri,
Bakterien der Familie Mycoplasmataceae, der Gattungen My
coplasma und Ureaplasma, insbesondere die Art Mycoplasma pneu
moniae,
Bakterien der Gattung Brucella,
Bakterien der Gattung Bordetella,
Bakterien der Familie Neisseriaceae, insbesondere der Gattun
gen Neisseria und Moraxella, insbesondere die Arten Neisseria
meningitides, Neisseria gonorrhoeae und Moraxella bovis,
Bakterien der Familie Vibrionaceae, insbesondere der Gattungen
Vibrio, Aeromonas, Plesiomonas und Photobacterium, insbesonde
re die Arten Vibrio cholerae, Vibrio anguillarum und Aeromonas
salmonicidas,
Bakterien der Gattung Campylobacter, insbesondere die Arten
Campylobacter jejuni, Campylobacter coli und Campylobacter fe
tus,
Bakterien der Gattung Helicobacter, insbesondere die Art Heli
cobacter pylori,
Bakterien der Familien Spirochaetaceae und der Leptospiraceae,
insbesondere der Gattungen Treponema, Borrelia und Leptospira,
insbesondere Borrelia burgdorferi,
Bakterien der Gattung Actinobacillus,
Bakterien der Familie Legionellaceae, der Gattung Legionella,
Bakterien der Familie Rickettsiaceae und Familie Bartonellä
ceae,
Bakterien der Gattungen Nocardia und Rhodococcus,
Bakterien der Gattung Dermatophilus,
Bakterien der Familie Pseudomonadaceae, insbesondere, der Gat
tungen Pseudomonas und Xanthomonas,
Bakterien der Familie Enterobacteriaceae, insbesondere der
Gattungen Escherichia, Klebstella, Proteus, Providencia, Sal
monella, Serratia und Shigella,
Bakterien der Familie Pasteurellaceae, insbesondere der Gat
tung Haemophilus,
Bakterien der Familie Micrococcaceae, insbesondere der Gattun
gen Micrococcus und Staphylococcus,
Bakterien der Familie Streptococcaceae, insbesondere der Gät
tungen Streptococcus und Enterococcus und
Bakterien der Familie Bacillaceae, insbesondere der Gattungen
Bacillus und Clostridium.They are therefore in particular as malaria prophylaxis and as prophylaxis of sleeping sickness and Chagas disease, toxoplasmosis, amoebic dysentery, leishmaniasis, trichomo niasis, pneumocystosis, balantidiosis, cryptospori diosis, sarcomocystosis, acanteglobe disease, coccidiosis, giardiosis and lambliosis. The active compounds according to the invention can be used in particular against the following bacteria:
Bacteria of the Propionibacteriaceae family, in particular of the Propionibacterium genus, in particular the Propionibacte rium acnes species,
Bacteria of the Actinomycetaceae family, in particular the Actinomyces gate,
Bacteria of the genus Corynebacterium, in particular the species Corynebacterium diphteriae and Corynebacterium pseudotubercu losis,
Bacteria of the family Mycobacteriaceae, of the genus Mycobacte rium, in particular the species Mycobacterium leprae, Mycobacte rium tuberculosis, Mycobacterium bovis and Mycobacterium avi um,
Bacteria of the family Chlamydiaceae, in particular the species Chlamydia trachomatis and Chlamydia psittaci,
Bacteria of the genus Listeria, in particular the species Listeria monocytogenes,
Bacteria of the species Erysipelthrix rhusiopathiae,
Bacteria of the genus Clostridium,
Bacteria of the genus Yersinia, of the species Yersinia pestis, Yersinia pseudotuberculosis, Yersinia enterocolitica and Yer sinia ruckeri,
Bacteria of the family Mycoplasmataceae, the genera My coplasma and Ureaplasma, especially the species Mycoplasma pneu moniae,
Bacteria of the genus Brucella,
Bacteria of the genus Bordetella,
Bacteria of the Neisseriaceae family, in particular of the Neisseria and Moraxella genus, in particular the Neisseria meningitides, Neisseria gonorrhoeae and Moraxella bovis species,
Bacteria of the Vibrionaceae family, in particular of the Vibrio, Aeromonas, Plesiomonas and Photobacterium genera, in particular the Vibrio cholerae, Vibrio anguillarum and Aeromonas salmonicidas species,
Bacteria of the genus Campylobacter, in particular the species Campylobacter jejuni, Campylobacter coli and Campylobacter fe tus,
Bacteria of the genus Helicobacter, in particular the species Heli cobacter pylori,
Bacteria of the Spirochaetaceae and Leptospiraceae families, in particular of the Treponema, Borrelia and Leptospira genera, in particular Borrelia burgdorferi,
Bacteria of the genus Actinobacillus,
Bacteria of the Legionellaceae family, the genus Legionella,
Bacteria of the Rickettsiaceae and Bartonellä ceae families,
Bacteria of the genera Nocardia and Rhodococcus,
Bacteria of the genus Dermatophilus,
Bacteria of the family Pseudomonadaceae, in particular of the genus Pseudomonas and Xanthomonas,
Bacteria of the Enterobacteriaceae family, in particular of the genera Escherichia, Klebstella, Proteus, Providencia, Sal monella, Serratia and Shigella,
Bacteria of the Pasteurellaceae family, especially the Gat tung Haemophilus,
Bacteria of the Micrococcaceae family, in particular of the genera Micrococcus and Staphylococcus,
Bacteria of the Streptococcaceae family, in particular the Streptococcus and Enterococcus and
Bacteria of the Bacillaceae family, especially the genera Bacillus and Clostridium.
Damit eignen sich Thiadiazolderivate zur Behandlung der Diph terie, der Acne vulgaris, der Listeriosen, des Rotlaufs bei Tieren, der Gasbrand beim Mensch und beim Tier, Pararauschbrand bei Mensch und Tier, Tuberkulose bei Mensch und Tier, Lepra, und weitere Mykobacteriosen bei Mensch und Tier, der Paratuberkulose der Tiere, Pest, mesenterialen Lym phadenitis und Pseudotuberkulose bei Mensch und Tier, Cholera, Legionärskrankheit, Borreliose bei Mensch und Tier, Leptospi rosen bei Mensch und Tier, Syphilis, Campylobacter-Enteritiden bei Mensch und Tier, Moraxella-Keratokonjung-tivitis und Sero sitis der Tiere, Brucellosen der Tiere und des Menschen, Milz brand bei Mensch und Tier, Aktinomykose bei Mensch und Tier, Streptotrichosen, Psittakose/Ornithose bei Tieren, Q-Fieber, Ehrlichiose.This makes thiadiazole derivatives suitable for the treatment of diph terie, Acne vulgaris, Listeriosen, Rotlauf Animals, the gas fire in humans and animals, Para-noise burn in humans and animals, tuberculosis in humans and animal, leprosy, and other mycobacteriosis in humans and Animal, paratuberculosis of animals, plague, mesenteric lym phadenitis and pseudotuberculosis in humans and animals, cholera, Legionnaires' disease, human and animal disease, Leptospi roses in humans and animals, syphilis, Campylobacter enteritis in humans and animals, Moraxella keratoconjungivitis and Sero sitis of animals, brucellosis of animals and humans, spleen fire in humans and animals, actinomycosis in humans and animals, Streptotrichoses, psittacosis / ornithosis in animals, Q fever, Ehrlichiosis.
Weiter ist der Einsatz nützlich bei der Helicobacter- Eradikationstherapie bei Ulcera des Magendarmtraktes.The use is also useful in the Helicobacter Eradication therapy for ulcers of the gastrointestinal tract.
Es können auch Kombinationen mit einem weiteren Antibiotikum zur Behandlung der obengenannten Erkrankungen eingesetzt wer den. Für Kombinationspräparate mit anderen Antiinfektiva eig nen sich insbesondere Isoniazid, Rifampicin, Ethambutol, Pyra zinamid, Streptomycin, Protionamid und Dapson zur Behandlung der Tuberkulose.Combinations with another antibiotic can also be used used to treat the above diseases the. For combination products with other anti-infectives especially isoniazid, rifampicin, ethambutol, pyra zinamid, streptomycin, protionamide and dapsone for treatment tuberculosis.
Die erfindungsgemäßen Wirkstoffe sind ferner insbesondere bei
Infektionen mit folgenden Viren einsetzbar:
Parvoviridae: Parvoviren, Dependoviren, Densoviren,
Adenoviridae: Adenoviren, Mastadenoviren, Aviadenoviren,
Papovaviridae: Papovaviren, insbesondere Papillomaviren (soge
nannte Warzenviren), Polyomaviren, insbesondere JC-Virus, BK-
Virus, und Miopapovaviren,
Herpesviridae: Alle Herpesviren, insbesondere Herpes-Simplex-
Viren, der Varizellen/Zoster-Viren, menschlicher Zytomegalie
virus, Epstein-Barr-Viren, alle humanen Herpesviren, humanes
Herpesvirus 6, Humanes Herpesvirus 7, humanes Herpesvirus 8,
Poxviridae: Pockenviren, Orthopox-, Parapox-, Molluscum-
Contagiosum-Virus, Aviviren, Capriviren, Leporipoxviren,
alle primär hepatotropen Viren, Hepatitisviren: Hepatitis-A-
Viren, Hepatitis-B-Viren, Hepatitis-C-Viren, Hepatitis-D-
Viren, Hepatitis-E-Viren, Hepatitis-F-Viren, Hepatits-G-Viren,
Hepadnaviren: sämtliche Hepatitisviren, Hepatitis-B-Virus, He
patitis-D-Viren,
Picornaviridae: Picornaviren, alle Enteroviren, alle Poliovi
ren, alle Coxsackieviren, alle Echoviren, alle Rhinoviren, He
patitis-A-Virus, Aphthoviren,
Calciviridae: Hepatitis-E-Viren,
Reoviridae: Reoviren, Orbiviren, Rotaviren,
Togaviridae: Togaviren, Alphaviren, Rubiviren, Pestiviren, Ru
bellavirus,
Flaviviridae: Flaviviren, FSME-Virus, Hepatitis-C-Virus,
Orthomyxoviridae: Alle Influenzaviren,
Paramyxoviridae: Paramyxoviren, Morbillivirus, Pneumovirus,
Masernvirus, Mumpsvirus,
Rhabdoviridae: Rhabdoviren, Rabiesvirus, Lyssavirus, viskulä
res Stomatitisvirus,
Coronaviridae: Coronaviren,
Bunyaviridae: Bunyaviren, Nairovirus, Phlebovirus, Uukuvirus,
Hantavirus, Hantaanvirus,
Arenaviridae: Arenaviren, lymphozytäres Choriomeningitis-
Virus,
Retroviridae: Retroviren, alle HTL-Viren, humanes T-cell Leu
kämievirus, Oncornaviren, Spumaviren, Lentiviren, alle HI-
Viren,
Filoviridae: Marburg- und Ebolavirus,
Slow-virus-Infektionen, Prionen,
Onkoviren und Leukämieviren.The active compounds according to the invention can also be used in particular for infections with the following viruses:
Parvoviridae: Parvoviruses, Dependoviruses, Densoviruses,
Adenoviridae: adenoviruses, mastadenoviruses, aviadenoviruses,
Papovaviridae: papovaviruses, in particular papillomaviruses (so-called wart viruses), polyomaviruses, in particular JC virus, BK virus, and miopapovaviruses,
Herpesviridae: all herpes viruses, in particular herpes simplex viruses, the varicella / zoster viruses, human cytomegalovirus, Epstein-Barr viruses, all human herpes viruses, human herpes virus 6, human herpes virus 7, human herpes virus 8,
Poxviridae: smallpox viruses, orthopox, parapox, molluscum contagiosum virus, aviviruses, capriviruses, leporipox viruses, all primarily hepatotropic viruses, hepatitis viruses: hepatitis A viruses, hepatitis B viruses, hepatitis C viruses - viruses, hepatitis E viruses, hepatitis F viruses, hepatits G viruses,
Hepadnaviruses: all hepatitis viruses, hepatitis B virus, He patitis D viruses,
Picornaviridae: Picornaviruses, all enteroviruses, all polioviruses, all Coxsackieviruses, all echoviruses, all rhinoviruses, He patitis A virus, aphthoviruses,
Calciviridae: hepatitis E viruses,
Reoviridae: reoviruses, orbiviruses, rotaviruses,
Togaviridae: Togaviruses, Alphaviruses, Rubiviruses, Pestiviruses, Ru bellavirus,
Flaviviridae: flaviviruses, TBE virus, hepatitis C virus,
Orthomyxoviridae: all influenza viruses,
Paramyxoviridae: paramyxoviruses, morbillivirus, pneumovirus, measles virus, mumps virus,
Rhabdoviridae: rhabdoviruses, rabies virus, lyssavirus, viscous stomatitis virus,
Coronaviridae: Coronaviruses,
Bunyaviridae: Bunyaviren, Nairovirus, Phlebovirus, Uukuvirus, Hantavirus, Hantaanvirus,
Arenaviridae: arenaviruses, lymphocytic choriomeningitis virus,
Retroviridae: retroviruses, all HTL viruses, human T-cell leukemia virus, oncornaviruses, spumaviruses, lentiviruses, all HI viruses,
Filoviridae: Marburg and Ebola viruses,
Slow virus infections, prions,
Oncoviruses and leukemia viruses.
Die erfindungsgemäßen Thiadiazolderivate sind somit zur Be
kämpfung folgender viraler Infekte geeignet:
Eradikation von Papillomaviren zur Vorbeugung von Tumoren,
insbesondere von Tumoren der Geschlechtsorgane verursacht
durch Papillomaviren beim Menschen, Eradikation von JC-Viren
und BK-Viren, Eradikation von Herpesviren, Eradikation humaner
Herpesviren 8 zur Behandlung der Kaposi-Sarkoma, Eradikation
von Zytomegalie-Viren vor Transplantationen, Eradikation von
Eppstein-Barr-Viren vor Transplantation und zur Vorbeugung von
Eppstein-Barr-Viren-assozierten Tumoren, Eradikation von Hepa
titisviren zur Behandlung von chronischen Leber-Erkrankungen
und zur Vorbeugung von Lebertumoren und Leberzirrhosen, Eradi
kation von Coxsackieviren bei Kardiomyopathien, Eradikation
von Coxsackieviren bei Diabetes-mellitus-Patienten, Eradikati
on von Immunschwäche-Viren in Mensch und Tier, Behandlung von
Begleitinfektionen in AIDS-Patienten, Behandlung von Entzün
dungen viraler Genese des Respirationstraktes (Larynxpapillo
me, Hyperplasien, Rhinitis, Pharyngitis, Bronchitis, Pneumoni
en), der Sinnesorgane (Keratokonjunktivitis), des Nervensy
stems (Poliomyelitis, Meningoenzephalitis, Enzephalitis, suba
kute sklerosierende Panenzephalitis, SSPE, progressive multi
fokale Leukoenzephalopathie, Lymphozytäre Choriomeningitis),
des Magen-Darm-Traktes (Stomatitis, Gingivostomatitis, Ösopha
gitis, Gastritis, Gastroenteritis, Durchfallerkrankungen), der
Leber und des Gallensystems (Hepatitis, Cholangitis, hepato
zelluläres Karzinom), des lymphatischen Gewebes (Mononukleose,
Lymphadenitis), des hämatopoetischen Systems, der Geschlechts
organe (Mumpsorchitis), der Haut (Warzen, Dermatitis, Herpes
labialis, Fieberbläschen, Herpes Zoster, Gürtelrose), der
Schleimhäute (Papillome, Konjunktivapapillome, Hyperplasien,
Dysplasien), des Herz-Blutgefäß-Systems (Arteriitis, Myokardi
tis, Endokarditis, Perikarditis), des Nieren-Harnweg-Systems,
der Geschlechtsorgane (Anogenitale Läsionen, Warzen, Genital
warzen, spitzen Kondylome, Dysplasien, Papillome, Zervix
dysplasien, Condylomata acuminata, Epidermodysplasia verruci
formis), der Bewegungsorgane (Myositis, Myalgien), Behandlung
der Maul- und Klauenseuche der Paarhufer, des Colorado-
Zeckenfiebers, des Dengue-Syndroms, des hämorrhagisches Fie
bers, der Frühsommermeningoenzephalitis (FSME) und des Gelb
fiebers.The thiadiazole derivatives according to the invention are therefore suitable for controlling the following viral infections:
Eradication of papillomaviruses for the prevention of tumors, in particular tumors of the genital organs caused by papillomaviruses in humans, eradication of JC viruses and BK viruses, eradication of herpes viruses, eradication of human herpes viruses 8 for the treatment of Kaposi's sarcoma, eradication of cytomegaloviruses Transplants, eradication of Eppstein-Barr viruses before transplantation and for the prevention of Eppstein-Barr virus-associated tumors, eradication of Hepa titis viruses for the treatment of chronic liver diseases and for the prevention of liver tumors and cirrhosis, eradication of Coxsackieviruses in cardiomyopathies, Eradication of Coxsackieviruses in diabetes mellitus patients, eradication of immunodeficiency viruses in humans and animals, treatment of concomitant infections in AIDS patients, treatment of inflammation of the viral genesis of the respiratory tract (laryngeal papillo me, hyperplasia, rhinitis, pharyngitis, bronchitis, pneumoni en), the sense organ e (keratoconjunctivitis), of the Nervensy stems (poliomyelitis, meningoencephalitis, encephalitis, suba kute sclerosing panencephalitis, SSPE, progressive multi-focal leukoencephalopathy, lymphocytic choriomeningitis), of the gastrointestinal tract (stomatitis, gingivostomatitis, Ösopha Gitis gastritis, gastroenteritis, diarrhea ), the liver and the biliary system (hepatitis, cholangitis, hepato cellular carcinoma), the lymphatic tissue (mononucleosis, lymphadenitis), the hematopoietic system, the genital organs (mumpsorchitis), the skin (warts, dermatitis, herpes labialis, cold sores, herpes Zoster, shingles), the mucous membranes (papillomas, conjunctival apillomas, hyperplasias, dysplasias), the cardiovascular system (arteritis, myocarditis, endocarditis, pericarditis), the kidney-urinary system, the genital organs (anogenital lesions, warts, genitalia warts, pointed condylomas, dysplasias, papillomas, cervical dysplasias, condylomata acuminata, Epidermodysplasia verruci formis), the locomotive organs (myositis, myalgia), treatment of foot and mouth disease of the cloven hoofed animals, Colorado tick fever, dengue syndrome, hemorrhagic fever, early summer meningoencephalitis (TBE) and yellow fever.
Die erfindungsgemäßen Thiadiazolderivaten, hierzu gehören auch Verbindungen, die bei Applikation die erfindungsgemäß verwen deten Verbindungen als Stoffwechselprodukte oder Abbauprodukte bereitstellen, auch "Prodrugs" genannt, können für die Verab reichung in irgendeiner geeigneten Weise analog zu bekannten antiinfektiös wirkenden Mitteln (gemischt mit einem nicht to xischen pharmazeutisch akzeptablen Träger) zubereitet werden.The thiadiazole derivatives according to the invention also include these Compounds that use the invention when applied compounds as metabolic products or degradation products provide, also called "prodrugs", can be used for the in any suitable manner analogous to known anti-infectious agents (mixed with a non-to xisch pharmaceutically acceptable carrier) are prepared.
Die Aktivität der Substanzen wird in einem Versuchssystem be stimmt. Dieses System beruht auf die Messung der Inhibition des Wachstums von Bakterien, Parasiten, Viren, Pilze oder Pflanzen in vitro. Hierzu werden zum Teil Versuchsverfahren verwendet, die dem Fachmann bekannt sind.The activity of the substances is in a test system Right. This system is based on the measurement of inhibition the growth of bacteria, parasites, viruses, fungi or Plants in vitro. To this end, test procedures are used in part used, which are known to the expert.
Zum Beispiel wird zur Bestimmung der Antimalaria Aktivität die Inhibition des Wachstums von Malaria Parasiten in Blutkulturen bestimmt.For example, to determine antimalaria activity Inhibition of the growth of malaria parasites in blood cultures certainly.
Die Bestimmung der antibakteriellen Aktivität beruht auf Mes sung der Hemmung von Bakterienwachstum auf Nährböden und in Flüssigkulturen.The determination of the antibacterial activity is based on Mes inhibition of bacterial growth on nutrient media and in Liquid cultures.
Die Bestimmung der antiviralen Aktivität beruht auf Inhibition der Bildung von viralen Elementen in Zellkulturen. The determination of the antiviral activity is based on inhibition the formation of viral elements in cell cultures.
Die Bestimmung der fungiziden Aktivität beruht auf Inhibition des Wachstums von Pilzen auf Nährböden und in Flüssigkulturen.The determination of the fungicidal activity is based on inhibition the growth of fungi on nutrient media and in liquid cultures.
Einige der Mikroorganismen, die untersucht werden sollen, kön nen nur in Tiermodellen untersucht werden. Hier werden die entsprechenden Modelle angewendet.Some of the microorganisms to be examined can can only be examined in animal models. Here are the corresponding models applied.
Substanzen, die eine Wirksamkeit in den in vitro Meßsystemen zeigen, werden in in vivo Modellen weiter untersucht. Die an tiparasitäre, antivirale, fungizide oder antibakterielle Akti vität wird in den entsprechenden Tiermodelle weiter evaluiert.Substances that are effective in in vitro measurement systems show are further investigated in in vivo models. The on tiparasitary, antiviral, fungicidal or antibacterial acti vity is further evaluated in the corresponding animal models.
Die pharmazeutisch wirksamen Mittel können in Form von pharma zeutischen Zubereitungen in Dosierungseinheiten zubereitet werden. Dies bedeutet, daß die Zubereitung in Form einzelner Teile, z. B. Tabletten, Dragees, Kapseln, Pillen, Suppositori en und Ampullen vorliegen, deren Wirkstoffgehalt einem Bruch teil oder einem Vielfachen einer Einzeldosis entsprechen. Die Dosierungseinheiten können z. B. 1, 2, 3 oder 4 Einzeldosen oder 1/2, 1/3 oder 1/4 einer Einzeldosis enthalten. Eine Ein zeldosis enthält vorzugsweise die Menge Wirkstoff, die bei ei ner Applikation verabreicht wird und die gewöhnlich einer gan zen, einer halben oder einem Drittel oder einem Viertel einer Tagesdosis entspricht.The pharmaceutically active agents can be prepared in the form of pharmaceutical preparations in dosage units. This means that the preparation in the form of individual parts, e.g. B. tablets, coated tablets, capsules, pills, suppositories and ampoules are present, the active ingredient content of which corresponds to a fraction or a multiple of a single dose. The dosage units can e.g. Example 1, 2, 3 or 4 individual doses or 1/2 1/3 or 1/4 of an individual dose. A single dose preferably contains the amount of active ingredient which is administered in one application and which usually corresponds to a whole, a half or a third or a quarter of a daily dose.
Unter nicht toxischen, inerten pharmazeutisch geeigneten Trä gerstoffen sind feste, halbfeste oder flüssige Verdünnungsmit tel, Füllstoffe und Formulierungshilfsmittel jeder Art zu ver stehen.Taking non-toxic, inert pharmaceutically acceptable drugs materials are solid, semi-solid or liquid diluents tel, fillers and formulation auxiliaries of all kinds stand.
Als bevorzugte pharmazeutische Zubereitungen seien Tabletten, Dragees, Kapseln, Pillen, Granulate, Suppositorien, Lösungen, Suspensionen und Emulsionen, Pasten, Salben, Gele, Cremes, Lo tions, Puder und Sprays genannt. Tabletten, Dragees, Kapseln, Pillen und Granulate können den oder die Wirkstoffe neben den üblichen Trägerstoffen enthalten, wie (a) Füll- und Streckmit tel, z. B. Stärken, Milchzucker, Rohrzucker, Glukose, Mannit und Kieselsäure, (b) Bindemittel, z. B. Carboxymethylcellulo se, Alginate, Gelatine, Polyvinylpyrrolidon, (c) Feuchthal temittel, z. B. Glycerin, (d) Sprengmittel, z. B. Agar-Agar, Calciumcarbonat und Natriumcarbonat, (e) Lösungsverzögerer, z. B. Paraffin und (f) Resorptionsbeschleuniger, z. B. quarternä re Ammoniumverbindungen, (g) Netzmittel, z. B. Cetylalkohol, Glycerinmonostearat, (h) Adsorptionsmittel, z. B. Kaolin und Bentonit und (1) Gleitmittel, z. B. Talkum, Calcium- und Ma gnesiumstearat und feste Polyethylenglykole oder Gemische der unter (a) bis (i) aufgeführten Stoffe.The preferred pharmaceutical preparations are tablets, Coated tablets, capsules, pills, granules, suppositories, solutions, Suspensions and emulsions, pastes, ointments, gels, creams, lo tion, powder and sprays called. Tablets, coated tablets, capsules, Pills and granules can be the active ingredient or ingredients in addition to the contain conventional carriers, such as (a) filling and stretching tel, e.g. B. starches, milk sugar, cane sugar, glucose, mannitol and silica, (b) binders, e.g. B. Carboxymethyl cellulo se, alginates, gelatin, polyvinylpyrrolidone, (c) damp means, e.g. B. glycerin, (d) disintegrant, e.g. B. agar, Calcium carbonate and sodium carbonate, (e) solution retarders, e.g. B. paraffin and (f) absorption accelerator, e.g. B. quaternary re ammonium compounds, (g) wetting agents, e.g. B. cetyl alcohol, Glycerol monostearate, (h) adsorbent, e.g. B. kaolin and Bentonite and (1) lubricants, e.g. B. talc, calcium and Ma magnesium stearate and solid polyethylene glycols or mixtures of substances listed under (a) to (i).
Die Tabletten, Dragees, Kapseln, Pillen und Granulate können mit den üblichen, gegebenenfalls Opakisierungsmittel enthal tenden Überzügen und Hüllen versehen sein und auch so zusam mengesetzt sein, daß sie den oder die Wirkstoffe nur oder be vorzugt in einem bestimmten Teil des Intestinaltraktes gegebe nenfalls verzögert abgeben, wobei als Einbettungsmassen z. B. Polymersubstanzen und Wachse verwendet werden können.The tablets, dragees, capsules, pills and granules can with the usual, optionally containing opacifiers tendency coatings and covers and so together be set that they only or be the active ingredients preferably in a certain part of the intestinal tract If necessary, deliver with a delay, with z. B. Polymer substances and waxes can be used.
Der oder die Wirkstoffe können gegebenenfalls mit einem oder mehreren der oben angegebenen Trägerstoffe auch in mikrover kapselter Form vorliegen.The active ingredient (s) can optionally be combined with an or several of the above-mentioned carriers also in microver encapsulated form.
Suppositorien können neben dem oder den Wirkstoffen die übli chen wasserlöslichen oder wasserunlöslichen Trägerstoffe ent halten, z. B. Polyethylenglykole, Fette, z. B. Kakaofett und höhere Ester (z. B. C14-Alkohol mit C16-Fettsäure) oder Gemische dieser Stoffe.Suppositories in addition to the active ingredient (s) can contain the usual water-soluble or water-insoluble carriers, e.g. B. polyethylene glycols, fats, e.g. B. cocoa fat and higher esters (z. B. C 14 alcohol with C 16 fatty acid) or mixtures of these substances.
Salben, Pasten, Cremes und Gele können neben dem oder den Wirkstoffen die üblichen Trägerstoffe enthalten, z. B. tieri sche und pflanzliche Fette, Wachse, Paraffine, Stärke, Tra gant, Cellulosederivate, Polyethylenglykole, Silikone, Bento nite, Kieselsäure, Talkum und Zinkoxid oder Gemische dieser Stoffe.Ointments, pastes, creams and gels can next to the or Active substances contain the usual carriers, e.g. B. tieri vegetable and vegetable fats, waxes, paraffins, starch, tra gant, cellulose derivatives, polyethylene glycols, silicones, bento nite, silica, talc and zinc oxide or mixtures of these Fabrics.
Puder und Sprays können neben dem oder den Wirkstoffen die üb lichen Trägerstoffe enthalten, z. B. Milchzucker, Talkum, Kie selsäure, Aluminiumhydroxid, Calciumsilikat und Polyamidpulver oder Gemische dieser Stoffe. Sprays können zusätzlich die üb lichen Treibmittel, z. B. Chlorfluorkohlenwasserstoffe, ent halten.Powders and sprays can in addition to the active ingredient (s) Lichen carriers included, for. B. milk sugar, talc, Kie silica, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these substances. Sprays can also be used union blowing agents, e.g. B. chlorofluorocarbons, ent hold.
Lösungen und Emulsionen können neben dem oder den Wirkstoffen die üblichen Trägerstoffe wie Lösungsmittel, Lösungsvermittler und Emulgatoren, z. B. Wasser, Ethylalkohol, Isopropylalkohol, Ethylcarbonat, Ethylacetat, Benzylalkohol, Benzylbenzoat, Pro pylenglykol, 1,3-Butylenglykol, Dimethylformamid, Öle, insbe sondere Baumwollsaatöl, Erdnußöl, Maiskeimöl, Olivenöl, Ricinusöl und Sesamöl, Glycerin, Glycerinformal, Tetrahydrb furfurylalkohol, Polyethylenglykole und Fettsäureester des Sorbitans oder Gemische dieser Stoffe enthalten.Solutions and emulsions can be added to the active ingredient (s) the usual carriers such as solvents, solubilizers and emulsifiers, e.g. B. water, ethyl alcohol, isopropyl alcohol, Ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, Pro pylene glycol, 1,3-butylene glycol, dimethylformamide, oils, esp special cottonseed oil, peanut oil, corn oil, olive oil, Castor oil and sesame oil, glycerin, glycerin formal, tetrahydrb furfuryl alcohol, polyethylene glycols and fatty acid esters of Contain sorbitans or mixtures of these substances.
Zur parenteralen Applikation können die Lösungen und Emulsio nen auch in steriler und blutisotonischer Form vorliegen.The solutions and emulsions can be used for parenteral administration are also available in sterile and blood isotonic form.
Suspensionen können neben dem oder den Wirkstoffen die übli chen Trägerstoffe wie flüssige Verdünnungsmittel, z. B. Was ser, Ethylalkohol, Propylenglykol, Suspendiermittel, z. B. ethoxylierte Isostearylalkohole, Polyoxyethylensorbit- und Sorbitan-Ester, mikrokristalline Cellulose, Aluminiummetahy droxid, Bentonit, Agar-Agar und Tragant oder Gemische dieser Stoffe enthalten.Suspensions can besides the active ingredient (s) the usual Chen carriers such as liquid diluents, e.g. B. What water, ethyl alcohol, propylene glycol, suspending agents, e.g. B. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and Sorbitan esters, microcrystalline cellulose, aluminum metal hydroxide, bentonite, agar and tragacanth or mixtures of these Contain substances.
Die genannten Formulierungsformen können auch Färbemittel, Konservierungsstoffe sowie geruchs- und geschmacksverbessernde Zusätze, z. B. Pfefferminzöl und Eukalyptusöl und Süßmittel, z. B. Saccharin, enthalten. The formulation forms mentioned can also contain colorants, Preservatives as well as odor and taste improving Additives, e.g. B. peppermint oil and eucalyptus oil and sweeteners, e.g. B. saccharin.
Die Wirkstoffe der Formel (I) sollen in den oben aufgeführten pharmazeutischen Zubereitungen, vorzugsweise in einer Konzen tration von etwa 0,1 bis 99,5 Gew.-%, vorzugsweise von etwa 0,5 bis 95 Gew.-%, der Gesamtmischung vorhanden sein.The active compounds of the formula (I) are intended to be those listed above pharmaceutical preparations, preferably in a concentrate tration of about 0.1 to 99.5 wt .-%, preferably of about 0.5 to 95% by weight of the total mixture may be present.
Die pharmazeutischen Zubereitungen können außer den Verbindun gen der Formel (I) auch weitere pharmazeutische Wirkstoffe enthalten.In addition to the compounds, the pharmaceutical preparations can gene of formula (I) also other active pharmaceutical ingredients contain.
Die Verbindungen können mit bisher beschriebenen Substanzen mit antibakterieller, antiviraler, antimyktoischer und antipa rasitärer Eigenschaften verwendet werden. Hierzu gehören ins besondere Verbindungen, die bereits in der Therapie Anwendung gefunden haben oder noch angewendet werden. Hierzu sind insbe sondere geeignet Stoffe, die in der in der Roten Liste oder in Simon/Stille, Antibiotika-Therapie in Klinik und Praxis, 9. Auflage 1998 Schattauer Verlag, oder unter http:/www. cu stoms. treas. gov/imp-exp/rulings/harmoniz/hrm 129. html im In ternet mitaufgeführt. Insbesondere können die Derivate mit Pe nicilline, Benzylpenicillin (Penicillin G), Phenoxypenicilli ne, Isoxazolylpenicilline, Aminopenicilline, Ampicillin, Amoxixillin, Bacampicillin, Carboxypenicillin, Ticarcillin, Temocillin, Acyalaminopenicilline, Azlocillin, Mezlocillin, Piperacillin, Apalcillin, Mecillinam, Cephalosporine, Cefazo lin-Gruppe, Cefuroxim-Gruppe, Cefoxitin-Gruppe, Cefoxitin, Ce fotetan, Cefmetazol, Latamoxef, Flomoxef, Cefotaxim-Guppe, Ce fozidim, Ceftazidim-Gruppe, Ceftazidim, Cefpirom, Cefepim, üb rige Cephalosporine, Cefsulodin, Cefoperazon, Oralcephalospo rine der Cefalexin-Gruppe, Loracarbef, Cefprozil, neue Oralce phalosporine mit erweitertem Spektrum, Cefixim, Cefpodoxim- Proxetil, Cefuroxim-Axetil, Cefetamet, Cefotiam-Hexetil, Cef dinir, Ceftibuten, andere β-Lactam-Antibiotika, Carbapenem, Imipenem /Cilastatin, Meropenem, Biapenem, Aztreonam, β- Lactamase-Hemmer; Clavulansäure/Amoxicillin, Clavulansäu re/Ticarcillin, Sulbactam/Ampicillin, Tazobactam/Piperacillin, Tetracycline, Oxytetracyclin, Rolitetraxyxlin, Doxycyclin, Mi nocyclin, Chloramphenicol, Aminoglykoside, Gentamicin, Tobramycin, Netilmicin, Amikacin, Spectinomyxin, Makrolide, Erythromycin, Clarithromycin, Roxithromycin, Azithromycin, Di rithromycin, Spiramycin, Josamycin, Lincosamide, Clindamycin, Fusidinsäure, Glykopeptid-Antibiotika, Vancomycin, Tecoplanin, Pristinamycin-Derivate, Fosfomycin, Antimikrobielle Folsäure antagonisten, Sulfonamide, Co-Trimoxazol, Trimethoprim, andere Diaminopyrimidin-Sulfonamid-Kombinationen, Nitrofurane, Nitro furantoin, Nitrofurazon, Gyrase-Hemmer (Chinolone), Norflox acin, Ciprofloxacin, Ofloxacin, Sparfloxacin, Enoxacin, Fler oxacin, Pefloxacin, Lomefloxacin, Bay Y3118, Nitroimidazole, antimykobakterielle Mittel, Isoniazid, Rifampicin, Rifabutin, Ethambutol, Pyrazinamid, Streptomycin, Capreomycin, Prothiona mid, Terizidon, Dapson, Clofazimin, Lokalantibiotika, Ba citracin, Tyrothricin, Polymyxine, Neomycin, Kanamycin, Paro momycin, Mupirocin, antivirale Mittel, Acyclovir, Ganciclovir, Azidothymidin, Didanosin, Zalcitabin, Thiacytidin, Stavudin, Ribavirin, Idoxuridin, Trifluridin, Foscarnet, Amantadin, In terferone, Tibol-Derivate, Proteinase-Inhibitoren, Antimykoti ka, Polyene, Amphothericin B, Nystatin, Natamycin, Azole, Azo le zur septischen Therapie, Miconazol, Ketoconazol, Itracona zol, Fluconazol, UK-109.496, Azole für lokale Anwendung, Clo trimazol, Econazol, Isoconazol, Oxiconazol, Bifonazol, Flucytosin, Griseofulvin, Ciclopiroxolamin, Tolnaftat, Nafti fin, Terbinafin, Amorolfin, Antrachinone, Betulinic acid, Se mianthrachinone, Xanthone, Naphtoquinone, Aryaminoalkohole, Chinin, Quinidine, Mefloquin, Halofantrin, Chloroquin, Amo diaquin, Acridin, Benzonaphthyridin, Mepacrin, Pyronaridin, Dapson, Sulfonamide, Sulfadoxin, Sulfalene, Trimethoprim, Pro guanil, Chlorproguanil, Diaminopyrimidine, Pyrimethamin, Pri maquin, Aminoquinoline, WR 238,605, Tetracyclin, Doxycyclin, Clindamycin, Norfloxacin, Ciprofloxacin, Ofloxacin, Artemisi nin, Dihydroartemisinin, 10b artemether, Arteether, Atrtesu nat, Atovaquon, Suramin, Melarsoprol, Nifurtmox, Stibogluco nat-Natrium, Pentamidin, Amphotericin B, Metronidazol, clio quinol, Mebendazol, Niclosamid, Praziquantel, Pyrantel, Tia bendazol, Diethylcarbamazin, Ivermectin, Bithionol, Oxamni quin, Metrifonat, Piperazin, Embonat.The compounds can with substances described so far with antibacterial, antiviral, antimyctoic and antipa razor properties are used. This includes ins special compounds that are already used in therapy have found or are still being used. In particular, particularly suitable substances that are in the Red List or in Simon / Stille, antibiotic therapy in clinic and practice, 9th edition 1998 Schattauer Verlag, or at http: / www. cu stoms. treas. gov / imp-exp / rulings / harmoniz / hrm 129. html in In ternet included. In particular, the derivatives with Pe nicilline, benzylpenicillin (penicillin G), phenoxypenicilli ne, isoxazolylpenicillins, aminopenicillins, ampicillins, Amoxixillin, bacampicillin, carboxypenicillin, ticarcillin, Temocillin, Acyalaminopenicilline, Azlocillin, Mezlocillin, Piperacillin, Apalcillin, Mecillinam, Cephalosporine, Cefazo lin group, cefuroxime group, cefoxitin group, cefoxitin, Ce fotetan, cefmetazole, latamoxef, flomoxef, cefotaxim group, Ce fozidim, ceftazidim group, ceftazidim, cefpirom, cefepim, ex cephalosporins, cefsulodin, cefoperazone, oral cephalospo rine of the cefalexin group, loracarbef, cefprozil, new oral phalosporins with extended spectrum, cefixime, cefpodoxime Proxetil, Cefuroxime-Axetil, Cefetamet, Cefotiam-Hexetil, Cef dinir, ceftibutene, other β-lactam antibiotics, carbapenem, Imipenem / cilastatin, meropenem, biapenem, aztreonam, β- Lactamase inhibitors; Clavulanic acid / amoxicillin, clavulanic acid right / ticarcillin, sulbactam / ampicillin, tazobactam / piperacillin, Tetracyclines, oxytetracycline, rolitetraxyxlin, doxycycline, Mi nocycline, chloramphenicol, aminoglycosides, gentamicin, Tobramycin, Netilmicin, Amikacin, Spectinomyxin, Macrolide, Erythromycin, Clarithromycin, Roxithromycin, Azithromycin, Di rithromycin, spiramycin, josamycin, lincosamide, clindamycin, Fusidic acid, glycopeptide antibiotics, vancomycin, tecoplanin, Pristinamycin derivatives, fosfomycin, antimicrobial folic acid antagonists, sulfonamides, co-trimoxazole, trimethoprim, others Diaminopyrimidine-sulfonamide combinations, nitrofurans, nitro furantoin, nitrofurazone, gyrase inhibitors (quinolones), norflox acin, ciprofloxacin, ofloxacin, sparfloxacin, enoxacin, Fler oxacin, pefloxacin, lomefloxacin, Bay Y3118, nitroimidazole, antifungal agents, isoniazid, rifampicin, rifabutin, Ethambutol, pyrazinamide, streptomycin, capreomycin, prothiona mid, terizidone, dapsone, clofazimin, local antibiotics, ba citracin, tyrothricin, polymyxins, neomycin, kanamycin, paro momycin, mupirocin, antiviral, acyclovir, ganciclovir, Azidothymidine, didanosine, zalcitabine, thiacytidine, stavudine, Ribavirin, Idoxuridine, Trifluridine, Foscarnet, Amantadine, In terferons, tibol derivatives, proteinase inhibitors, antifungals not specified, polyenes, amphothericin B, nystatin, natamycin, azoles, azo oils for septic therapy, miconazole, ketoconazole, itracona zol, fluconazole, UK-109,496, azoles for local use, Clo trimazole, econazole, isoconazole, oxiconazole, bifonazole, Flucytosine, griseofulvin, ciclopiroxolamine, tolnaftate, nafti fin, terbinafine, amorolfine, antrachinones, betulinic acid, Se mianthraquinones, xanthones, naphtoquinones, aryamino alcohols, Quinine, Quinidine, Mefloquine, Halofantrine, Chloroquine, Amo diaquine, acridine, benzonaphthyridine, mepacrine, pyronaridine, Dapsone, sulfonamides, sulfadoxine, sulfalenes, trimethoprim, Pro guanil, chlorproguanil, diaminopyrimidines, pyrimethamine, Pri maquin, aminoquinoline, WR 238.605, tetracycline, doxycycline, Clindamycin, norfloxacin, ciprofloxacin, ofloxacin, artemisi nin, dihydroartemisinin, 10b artemether, Arteether, Atrtesu nat, Atovaquon, Suramin, Melarsoprol, Nifurtmox, Stibogluco nat sodium, pentamidine, amphotericin B, metronidazole, clio quinol, mebendazole, niclosamide, praziquantel, pyrantel, Tia bendazole, diethylcarbamazine, ivermectin, bithionol, oxamni quin, metrifonate, piperazine, embonate.
Ferner können die Thiadiazolderivaten in den pharmazeutischen Mitteln in Kombination mit Sulfonamid, Sulfadoxin, Artemisi nin, Atovaquon, Chinin, Chloroquin, Hydroxychloroquin, Meflo quin, Halofantrin, Pyrimethamin, Armesin, Tetracycline, Doxy cyclin, Proguanil, Metronidazol, Praziquantil, Niclosamid, Me bendazol, Pyrantel, Tiabendazol, Diethylcarbazin, Piperazin, Pyrivinum, Metrifonat, Oxamniquin, Bithionol oder Suramin oder mehreren dieser Substanzen vorliegen.Furthermore, the thiadiazole derivatives in the pharmaceutical Agents in combination with sulfonamide, sulfadoxine, Artemisi nin, atovaquone, quinine, chloroquine, hydroxychloroquine, meflo quin, halofantrine, pyrimethamine, armesin, tetracycline, doxy cyclin, proguanil, metronidazole, praziquantil, niclosamide, Me bendazole, pyrantel, tiabendazole, diethylcarbazine, piperazine, Pyrivinum, Metrifonat, Oxamniquin, Bithionol or Suramin or several of these substances are present.
Die Herstellung der oben aufgeführten pharmazeutischen Zube reitungen erfolgt in üblicher Weise nach bekannten Methoden, z. B. durch Mischen des oder der Wirkstoffe mit dem oder den Trägerstoffen.The manufacture of the pharmaceutical accessories listed above Horse riding is done in the usual way according to known methods, e.g. B. by mixing the active ingredient or ingredients with the or Carriers.
Die genannten Zubereitungen können bei Mensch und Tier entwe der oral, rektal, parenteral (intravenös, intramuskulär, sub kutan), intracisternal, intravaginal, intraperitoneal, lokal (Puder, Salbe, Tropfen) und zur Therapie von Infektionen in Hohlräumen, Körperhöhlen angewendet werden. Als geeignete Zu bereitungen kommen Injektionslösungen, Lösungen und Suspensio nen für die orale Therapie, Gele, Aufgußformulierungen, Emul sionen, Salben oder Tropfen in Frage. Zur lokalen Therapie können ophtalmologische und dermatologische Formulierungen, Silber- und andere Salze, Ohrentropfen, Augensalben, Puder oder Lösungen verwendet werden. Bei Tieren kann die Aufnahme auch über das Futter oder Trinkwasser in geeigneten Formulie rungen erfolgen. Ferner können Gele, Pulver, Puder, Tabletten, Retard-Tabletten, Premixe, Konzentrate, Granulate, Pellets, Tabletten, Boli, Kapseln, Aerosole, Sprays, Inhalate bei Mensch und Tier angewendet werden. Ferner können die erfin dungsgemäßen Verbindungen in andere Trägermaterialien wie zum Beispiel Kunststoffe, (Kunststoffketten zur lokalen Therapie), Kollagen oder Knochenzement eingearbeitet werden.The preparations mentioned can be used in humans and animals the oral, rectal, parenteral (intravenous, intramuscular, sub cutaneous), intracisternal, intravaginal, intraperitoneal, local (Powder, ointment, drops) and for the treatment of infections in Cavities, body cavities are applied. As a suitable addition Preparations come with injection solutions, solutions and suspensions NEN for oral therapy, gels, infusion formulations, emul ions, ointments or drops. For local therapy ophthalmic and dermatological formulations, Silver and other salts, ear drops, eye ointments, powder or solutions are used. In animals, the intake also in suitable form via the feed or drinking water take place. Gels, powders, powders, tablets, Prolonged-release tablets, premixes, concentrates, granules, pellets, Tablets, boluses, capsules, aerosols, sprays, inhalants Humans and animals can be used. Furthermore, the inventions compounds according to the invention in other carrier materials such as Example plastics, (plastic chains for local therapy), Collagen or bone cement can be incorporated.
Im allgemeinen hat es sich sowohl in der Human- als auch in der Veterinärmedizin als vorteilhaft erwiesen; den oder die Wirkstoffe der Formel (I) in Gesamtmengen von etwa 0,05 bis etwa 600, vorzugsweise 0,5 bis 200 mg/kg Körpergewicht je 24 Stunden, gegebenenfalls in Form mehrerer Einzelgaben, zur Er zielung der gewünschten Ergebnisse zu verabreichen. Eine Ein zelgabe enthält den oder die Wirkstoffe vorzugsweise in Mengen von etwa 1 bis etwa 200, insbesondere 1 bis 60 mg/kg Körperge wicht. Es kann jedoch erforderlich sein, von den genannten Do sierungen abzuweichen, und zwar in Abhängigkeit von der Art und dem Körpergewicht des zu behandelnden Patienten, der Art und der Schwere der Erkrankung, der Art der Zubereitung und der Applikation des Arzneimittels sowie dem Zeitraum bzw. In tervall, innerhalb welchem die Verabreichung erfolgt.In general, it has been in both human and proven beneficial to veterinary medicine; the or the Active substances of the formula (I) in total amounts from about 0.05 to about 600, preferably 0.5 to 200 mg / kg body weight per 24 Hours, possibly in the form of several individual gifts, for Er to deliver the desired results. An on zelgabe contains the active ingredient (s) preferably in quantities from about 1 to about 200, especially 1 to 60 mg / kg body weight important. However, it may be necessary to do so from the above deviations depending on the type and the body weight of the patient to be treated, Art and the severity of the disease, the type of preparation and the application of the drug and the period or in interval within which the administration takes place.
So kann es in einigen Fällen ausreichend sein, mit weniger als der obengenannten Menge Wirkstoff auszukommen, während in an deren Fällen die oben angeführte Wirkstoffmenge überschritten werden muß. Die Festlegung der jeweils erforderlichen optima len Dosierung und Applikationsart der Wirkstoffe kann durch den Fachmann aufgrund seines Fachwissens erfolgen.So in some cases it may be sufficient with less than the above amount of active ingredient to get by while in at whose cases exceeded the amount of active ingredient mentioned above must become. The determination of the optima required in each case len dosage and type of application of the active ingredients can by the specialist on the basis of his specialist knowledge.
Die erfindungsgemäßen Verbindungen können in den üblichen Kon zentrationen und Zubereitungen bei Tieren zusammen mit dem Futter bzw. mit Futterzubereitungen oder mit dem Trinkwasser gegeben werden.The compounds of the invention can in the usual Kon concentrations and preparations in animals together with the Feed or with feed preparations or with drinking water are given.
Claims (11)
in der n eine ganze Zahl von 0 bis 4 ist,
und
in der R1, R2, R3, R4, R5 und R6 gleich oder verschieden sind und aus der Gruppe ausgewählt sind, die aus Wasserstoff, substituierten und unsubstituierten Alkylresten, substitu ierten und unsubstituierten Alkoxyresten, substituierten oder unsubstituierten Cycloalkyl-(C0-26)-alkylresten, sub stituierten und unsubstituierten Cycloalkyl-(C0-26)- alkoxyresten und substituierten oder unsubstituierten Acyl resten und Halogen besteht, wobei jeder Alkylrest, jeder Alkoxyrest und jeder Acylrest verzweigt oder unverzweigt und jeder Alkylrest, jeder Acylrest, jeder Alkoxyrest und jede Cycloalkylgruppe gesättigt oder mit ein oder mehreren Doppel- oder Dreifachbindungen ungesättigt sein kann und ein oder zwei Kohlenstoffatome der Cycloalkylgruppen durch Stickstoff-, Sauerstoff- oder Schwefelatome ersetzt sein können,
zur Behandlung von infektiösen Prozessen bei Mensch und Tier, die durch Viren, Bakterien, Pilze oder Parasiten her vorgerufen werden.1. Use of thiadiazole derivatives of the general formula (I)
in which n is an integer from 0 to 4,
and
in which R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are identical or different and are selected from the group consisting of hydrogen, substituted and unsubstituted alkyl radicals, substituted and unsubstituted alkoxy radicals, substituted or unsubstituted cycloalkyl radicals (C 0-26 ) alkyl radicals, substituted and unsubstituted cycloalkyl (C 0-26 ) alkoxy radicals and substituted or unsubstituted acyl radicals and halogen, where each alkyl radical, each alkoxy radical and each acyl radical is branched or unbranched and each alkyl radical, each Acyl radical, any alkoxy radical and any cycloalkyl group may be saturated or unsaturated with one or more double or triple bonds and one or two carbon atoms of the cycloalkyl groups may be replaced by nitrogen, oxygen or sulfur atoms,
for the treatment of infectious processes in humans and animals caused by viruses, bacteria, fungi or parasites.
Priority Applications (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19903398A DE19903398A1 (en) | 1999-01-29 | 1999-01-29 | Use of thiadiazole derivatives for the prophylactic and therapeutic treatment of infections |
PCT/EP2000/000613 WO2000044359A2 (en) | 1999-01-29 | 2000-01-27 | Utilisation of thiadizole derivatives for the prophylactic and therapeutic treatment of infections |
AU27989/00A AU2798900A (en) | 1999-01-29 | 2000-01-27 | Utilisation of thiadizole derivatives for the prophylactic and therapeutic treatment of infections |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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DE19903398A DE19903398A1 (en) | 1999-01-29 | 1999-01-29 | Use of thiadiazole derivatives for the prophylactic and therapeutic treatment of infections |
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DE19903398A1 true DE19903398A1 (en) | 2000-08-10 |
Family
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DE19903398A Ceased DE19903398A1 (en) | 1999-01-29 | 1999-01-29 | Use of thiadiazole derivatives for the prophylactic and therapeutic treatment of infections |
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AU (1) | AU2798900A (en) |
DE (1) | DE19903398A1 (en) |
WO (1) | WO2000044359A2 (en) |
Cited By (5)
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WO2002100851A3 (en) * | 2001-06-11 | 2003-02-27 | Shire Biochem Inc | Thiophene derivatives as antiviral agents for flavivirus infection |
US7402608B2 (en) | 2002-12-10 | 2008-07-22 | Virochem Pharma Inc. | Compounds and methods for the treatment or prevention of Flavivirus infections |
US7569600B2 (en) | 2005-05-13 | 2009-08-04 | Virochem Pharma Inc. | Compounds and methods for the treatment of prevention of Flavivirus infections |
US8003685B2 (en) | 2006-11-15 | 2011-08-23 | Vertex Pharmaceuticals (Canada) Incorporated | Thiophene analogues for the treatment or prevention of flavivirus infections |
US8329924B2 (en) | 2001-06-11 | 2012-12-11 | Vertex Pharmaceuticals (Canada) Incorporated | Compounds and methods for the treatment or prevention of Flavivirus infections |
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Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH07233069A (en) * | 1994-02-18 | 1995-09-05 | Sagami Chem Res Center | 5-lipoxygenase inhibitor containing 1,2,3-thiadiazole derivative as active ingredient |
JPH07233157A (en) * | 1994-02-18 | 1995-09-05 | Sagami Chem Res Center | 1,2,3-thiadiazole derivative |
-
1999
- 1999-01-29 DE DE19903398A patent/DE19903398A1/en not_active Ceased
-
2000
- 2000-01-27 AU AU27989/00A patent/AU2798900A/en not_active Abandoned
- 2000-01-27 WO PCT/EP2000/000613 patent/WO2000044359A2/en active Application Filing
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EP2363396A1 (en) * | 2001-06-11 | 2011-09-07 | Virochem Pharma Inc. | Thiophene derivatives as antiviral agents for flavivirus infection |
US6881741B2 (en) | 2001-06-11 | 2005-04-19 | Virochem Pharma Inc. | Compounds and methods for the treatment or prevention of Flavivirus infections |
EA007484B1 (en) * | 2001-06-11 | 2006-10-27 | Вирокем Фарма Инк. | Compounds and methods for the treatment or prevention of flavivirus infections |
WO2002100851A3 (en) * | 2001-06-11 | 2003-02-27 | Shire Biochem Inc | Thiophene derivatives as antiviral agents for flavivirus infection |
US8329924B2 (en) | 2001-06-11 | 2012-12-11 | Vertex Pharmaceuticals (Canada) Incorporated | Compounds and methods for the treatment or prevention of Flavivirus infections |
EP2206709A3 (en) * | 2001-06-11 | 2011-06-29 | Virochem Pharma Inc. | Thiophene derivatives as antiviral agents for flavivirus infection |
US7985769B2 (en) | 2001-06-11 | 2011-07-26 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of Flavivirus infections |
US8357718B2 (en) | 2002-12-10 | 2013-01-22 | Vertex Pharmaceuticals (Canada) Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
US7402608B2 (en) | 2002-12-10 | 2008-07-22 | Virochem Pharma Inc. | Compounds and methods for the treatment or prevention of Flavivirus infections |
US8829030B2 (en) | 2002-12-10 | 2014-09-09 | Vertex Pharmaceuticals (Canada) Incorporated | Compounds and methods for the treatment or prevention of Flavivirus infections |
US8158675B2 (en) | 2005-05-13 | 2012-04-17 | Vertex Pharmaceuticals (Canada) Incorporated | Compounds and methods for the treatment or prevention of Flavivirus infections |
US7569600B2 (en) | 2005-05-13 | 2009-08-04 | Virochem Pharma Inc. | Compounds and methods for the treatment of prevention of Flavivirus infections |
US8674118B2 (en) | 2005-05-13 | 2014-03-18 | Vertex Pharmaceuticals Incorporated | Compounds and methods for the treatment or prevention of flavivirus infections |
US8003685B2 (en) | 2006-11-15 | 2011-08-23 | Vertex Pharmaceuticals (Canada) Incorporated | Thiophene analogues for the treatment or prevention of flavivirus infections |
US8269014B2 (en) | 2006-11-15 | 2012-09-18 | Vertex Pharmaceuticals (Canada) Incorporated | Thiophene analogues for the treatment or prevention of flavivirus infections |
US8658674B2 (en) | 2006-11-15 | 2014-02-25 | Vertex Pharmaceuticals Incorporated | Thiophene analogues for the treatment or prevention of flavivirus infections |
Also Published As
Publication number | Publication date |
---|---|
WO2000044359A3 (en) | 2000-09-28 |
WO2000044359A2 (en) | 2000-08-03 |
AU2798900A (en) | 2000-08-18 |
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