Claims
- 1. A compound of the formula I:
- 2. The compound of claim 1 wherein
a) X is CN, OH, CH3, adenosyl or L-T; b) M is 5,6-dimethylbenzimidazole; c) K is C(OH)H; d) E is O; e) G1 is hydrogen, alkyl, acyl, silyl, mono-, di- or tri-phosphate or L-T f) Y1, Y2, Y3, Y4, Y5, Y6 and Y7 are O; g) V1, V2, V3, V4, V5, V6, V7 and V8 are independently NJ3; h) R1, R2, R4, R5, R8, R9, R11, R12 and R15 are independently methyl; i) R3, R6, R7, R10, R13 and R14 are independently hydrogen; and j) Z1, Z2, Z3, Z4, Z5, Z7 and Z8 are independently hydrogen or L-T.
- 3. The compound of claim 1 wherein, M is a purine or pyrimidine.
- 4. The compound of claim 1 wherein M is 5,6-dimethylbenzimidazole.
- 5. The compound of claims 1 wherein, X is not L-T.
- 6. The compound of claim 1 wherein at least one of Z1, Z2, Z4 or Z5 is independently L-T.
- 7. The compound of claim 1 wherein at least two of Z1, Z2, Z4 or Z5 are independently L-T.
- 8. The compound of claim 6 or 7 wherein L is a bond.
- 9. The compound of claim 6 or 7 wherein L is not a bond.
- 10. The compound of claim 9 wherein at least one L is of the formula W—A—Q wherein A is (C1-C24)alkyl, (C2-C24)alkenyl, (C2-C24)alkynyl, (C3-C8)cycloalkyl, or (C6-C10)aryl, wherein W and Q are each independently —N(R)C(═O)—, —C(═O)N(R)—, —OC(═O)—, —C(═O)O—, —O—, —S—, —S(O)—, —S(O)2—, —N(R)—, —C(═O)—, or a direct bond; wherein each R is independently H or (C1-C6)alkyl.
- 11. The compound of claim 10 wherein at least one of W and Q is independently —NR— or —COO—.
- 12. The compound of claim 10 wherein A is a (C1-C24)alkyl.
- 13. The compound of claim 9 wherein at least one L is about 5 angstroms to about 50 angstroms, in length, inclusive.
- 14. The compound of claim 9 wherein at least one L is a divalent radical formed from a peptide.
- 15. The compound of claim 9 wherein at least one L is a divalent radical formed from about 2-25 amino acids.
- 16. The compound of claim 14 or 15 wherein the divalent radical is a 1,ω-divalent radical.
- 17. The compound of claim 9 wherein at least one L is poly-L-glutamic acid, poly-L-aspartic acid, poly-L-histidine, poly-L-omithine, poly-L-serine, poly-L-threonine, poly-L-tyrosine, poly-L-leucine, poly-L-lysine-L-phenylalanine, poly-L-lysine or poly-L-lysine-L-tyrosine.
- 18. The compound of claim 17 wherein L is poly-L-lysine.
- 19. The compound of claim 18 wherein the poly-L-lysine contains about 8-11 residues.
- 20. The compound of claim 6 or 7 wherein Z1 is L-T.
- 21. The compound of claim 6 or 7 wherein Z2 is L-T.
- 22. The compound of claim 6 or 7 wherein Z4 is L-T.
- 23. The compound of claim 6 or 7 wherein Z5 is L-T.
- 24. The compound of claim 6 or 7 wherein Z2 and Z4 are independently L-T.
- 25. The compound of claim 1 wherein at least one T is independently an aminoglycoside, β-lactam antibiotic, cephalosporin, macrolide, miscellaneous antibiotic, penicillin, tetracycline, antifungal, antimalarial agent, antituberculosis agent, antiviral, leprostatic, miscellaneous anti-infectives, quinolines, sulfonamide, urinary anti-infective, nasal antibiotic, opthalmic antibiotic, opthalmic antiviral, opthalmic quinoline, opthalmic sulfonamide, skin and mucous membrane antibiotic, skin and mucous membrane antifungal, skin and mucous membrane antiviral, skin and mucous membrane miscellaneous anti-infective, skin and mucous membrane scabicide or pedulicide, skin and mucous membrane anti-neoplast, nitrofiaran, or oxazolidinone, or a pharmaceutically acceptable residue thereof.
- 26. The compound of claim 1 wherein at least one T is independently Amikacin, Garamycin, Nebcin, Netromycin, Streptomycin Sulfate, TOBI, Azactam, Cefotan, Lorabid, Mefoxin, Merrem, Primaxin, Ancef, Ceclor, Cedax, Cefizox, Cefobid, Ceftin, Cefzil, Ceptaz, Claforan, Duricef, Fortaz, Keflex, Keftab, Kefurox, Kefzol, Mandol, Maxipime, Monocid, Omnicef, Rocephin, Suprax, Tazicef, Tazidime, Vantin, Zinacef, Cefpodoxime Proxetil, Cefprozil, Cephalexin Monohydrate, Biaxin, Dynabac, E.E.S. 200, E.E.S. 400, Ery-Ped 200 and EryPed 400, Ery-Tab, Erythrocin Stearate, Erythromycin, Ilosone, PCE Dispertab, Pedizole, Tao, Azithromycin, Clarithromycin, and Erythromycin, Cleocin HCl, Cleocin Phosphate, Coly-Mycin M, Seromycin, Vancocin HCl, Amoxil, Augmentin, Bicillin C-R 900/300, Bicillin C-R, Bicillin L-A, Geocillin, Mezlin, Omnipen, Pen-Vee K, Pfizerpen, Pipracil, Spectrobid, Ticar, Timentin, Unasyn, Zosyn, Amoxicillin/Clavulanic Acid, Amoxicillin Trihydrate, Ampicillin, Dicloxacillin Sodium, Penicillin V Potassium, Acbromycin, Declomycin, Dynacin, Minocin, Monodox, Terramycin, Vectrin, Vibramycin Calcium, Vibramycin Hyclate, Vibramycin Monohydrate, Vibra-Tabs, Demeclocycline HCL, Doxycycline, Minocyline HCL, Oxytetracycline HCL, Tetracycline, Lincomycins, Clindamycin, Abelcet, AmBisome, Amphotec, Ancobon, Diflucan, Fulvicin P/G, Fulvicin P/G 165 and 330, Grifulvin V, Gris-PEG, Lamisil, Nizoral, Amphotericin B, Clotrimazole, Dapsone, Fluconazole, Flucytosine, Miconazole, Nystatin, Sporanox, Aralen hydrochloride, Aralen phosphate, Daraprim, Lariam, Plaquenil, Capastat sulfate, Myambutol, Mycobutin, Nydrazid, Paser, Priftin, Pyrazinamide, Rifadin, Rifadin IV, Rifamate, Rifater, Seromycin, Tice BCG, Aminosalicylate Sodium, Cycloserine, Isoniazid, Rifampin, Methenamine, Trecator-SC, Alferon N, Crixivan, Cytovene, Cytovene-IV, Epivir, Famvir, Flumadine, Foscavir, Hivid, Intron A, Invirase, Norvir, Rebetron, Rescriptor, Retrovir, Retrovir IV, Symmetrel, Synagis, Valtrex, Videx, Viracept, Viramune, Virazole, Vistide, Zerit, Amantadine HCl, Lamiduvine, Zovirax, Dapsone, Daraprim, Flagyl 375, Flagyl, Furoxone, Mepron, Neutrexin, Cipro, Floxin, Levaquin, Mazaquin, Noroxin, Penetrex, Raxar, Trovan, Zagam, Bactrim, Bactrim DS, Pediazole, Septra, Septra DS, Co-Trimoxazole, Erythromycin/Sulfioxazole, Sulfadiazine, Sulfamethoxazole, Sulfapyridine, Sulfisoxazole, Furadantin, Macrobid, Macrodantin, Monurol, NegGram, Septra, Septra DS, Urised, Urobiotic-250, Uroqid, Vira-A, Chibroxin, Chibroxan, Blephamide, A/T/S, Benzamycin, Betadine, Cleocin T, Clindets, Emgel, Erycette, Klaron, Mycostatin, Theramycin Z, T-Stat, Terramycin, Exelderm, Fungizone, Lamisil, Loprox, Lotrimin, Lotrisone, Mentax, Monistat-Derm, Mycelex, Mycostatin, Naftin, Nizoral, Nystop, Oxistat, Selsun Rx, Spectazole, Denavir, Zovirax, Benzashave, Betadine, Betasept, Cetaphil, Clorpactin, Dapsone, Desquam-E, Desquam-X, Hibiclens, Hibistat, Impregon, MetroCream, MetroGel, Noritate, pHisoHex, Sulfacet-R, Sulfamylon, Triaz, Vanoxide-HC, Acticin, Elimite, Eurax, Lindane, Efudex, Fluoroplex, Zyvox, or Nitrofurantoin, or a pharmaceutically acceptable residue thereof.
- 27. The compound of claim 1 wherein at least one T is independently Ciprofloxacin, Levofloxacin, Ofloxacin or Sparfloxacin, or a pharmaceutically acceptable residue thereof.
- 28. The compound of claim 1 wherein the Z1, Z2, Z3, Z4, Z5, Z7, Z8 or G1 moiety that is not L-T can further independently be L-T′ wherein T′ is an imaging agent, optionally bound through a chelating moiety.
- 29. The compound of claim 28 wherein the imaging agent is bound through a chelating moiety.
- 30. The compound of claim 29 wherein the chelating moiety is DPTA.
- 31. The compound of claim 29 wherein the imaging agent is a detectable radionuclide or a paramagnetic metal atom.
- 32. The compound of claim 31 wherein the detectable radionuclide or a paramagnetic metal atom is Technetium-99m, Indium-111 or Gadolinium-157.
- 33. The compound of claim 28, wherein the imaging agent is not bound through a chelating moiety.
- 34. The compound of claim 28 wherein the imaging agent is a non-metallic radionuclide.
- 35. The compound of claim 34 wherein the non-metallic radionuclide is carbon-11, fluorine-18, bromine-76, iodine-123 or iodine-124.
- 36. The compound of claim 28, wherein at least one of Z1, Z2, Z4 or Z5 is not L-T and is independently L-T′, wherein T′ is the imaging agent.
- 37. The compound of claim 37 wherein L is a bond.
- 38. The compound of claim 37 wherein L is not a bond.
- 39. A pharmaceutical composition for the treatment, prophylaxis or diagnosis of an infection in a host comprising the compound of any one of the preceding claims 1-38, or its pharmaceutically acceptable salt, together with a pharmaceutically acceptable carrier or diluent.
- 40. A pharmaceutical composition for the treatment, prophylaxis or diagnosis of an infection in a host comprising the compound of any one of the preceding claims 1-38, or its pharmaceutically acceptable salt, in combination with one or more antibiotic.
- 41. The composition of claim 40 wherein the antibiotic is an aminoglycoside, β-lactam antibiotic, cephalosporin, macrolide, miscellaneous antibiotic, penicillin, tetracycline, antifungal, antimalarial agent, antituberculosis agent, antiviral, leprostatic, miscellaneous anti-infectives, quinoline, sulfonamide, urinary anti-infective, nasal antibiotic, opthalmic antibiotic, opthalmic antiviral, opthalmic quinoline, opthaimic sulfonamide, skin and mucous membrane antibiotic, skin and mucous membrane antifungal, skin and mucous membrane antiviral, skin and mucous membrane miscellaneous anti-infective, skin and mucous membrane scabicide or pedulicide, skin and mucous membrane anti-neoplast, nitrofuran, or oxazolidinone, or a pharmaceutically acceptable residue thereof.
- 42. The composition of claim 40 wherein the antibiotic is Amikacin, Garamycin, Nebcin, Netromycin, Streptomycin Sulfate, TOBI, Azactam, Cefotan, Lorabid, Mefoxin, Merrem, Primaxin, Ancef, Ceclor, Cedax, Cefizox, Cefobid, Ceftin, Cefzil, Ceptaz, Claforan, Duricef, Fortaz, Keflex, Keftab, Kefurox, Kefzol, Mandol, Maxipime, Monocid, Onmicef, Rocephin, Suprax, Tazicef, Tazidime, Vantin, Zinacef, Cefpodoxime Proxetil, Cefprozil, Cephalexin Monohydrate, Biaxin, Dynabac, E.E.S. 200, E.E.S. 400, Ery-Ped 200 and EryPed 400, Ery-Tab, Erythrocin Stearate, Erythromycin, Ilosone, PCE Dispertab, Pedizole, Tao, Azithromycin, Clarithromycin, and Erythromycin, Cleocin HCl, Cleocin Phosphate, Coly-Mycin M, Seromycin, Vancocin HCl, Amoxil, Augmentin, Bicillin C-R 900/300, Bicillin C-R, Bicillin L-A, Geocillin, Mezlin, Omnipen, Pen-Vee K, Pfizerpen, Pipracil, Spectrobid, Ticar, Timentin, Unasyn, Zosyn, Amoxicillin/Clavulanic Acid, Amoxicillin Trihydrate, Ampicillin, Dicloxacillin Sodium, Penicillin V Potassium, Achromycin, Declomycin, Dynacin, Minocin, Monodox, Terramycin, Vectrin, Vibramycin Calcium, Vibramycin Hyclate, Vibramycin Monohydrate, Vibra-Tabs, Demeclocycline HCL, Doxycycline, Minocyline HCL, Oxytetracycline HCL, Tetracycline, Lincomycins, Clindamycin, Abelcet, AmBisome, Amphotec, Ancobon, Diflucan, Fulvicin P/G, Fulvicin P/G 165 and 330, Grifulvin V, Gris-PEG, Lamisil, Nizoral, Amphotericin B, Clotrimazole, Dapsone, Fluconazole, Flucytosine, Miconazole, Nystatin, Sporanox, Aralen hydrochloride, Aralen phosphate, Daraprim, Lariam, Plaquenil, Capastat sulfate, Myambutol, Mycobutin, Nydrazid, Paser, Priftin, Pyrazinamide, Rifadin, Rifadin IV, Rifamate, Rifater, Seromycin, Tice BCG, Aminosalicylate Sodium, Cycloserine, Isoniazid, Rifampin, Methenamine, Trecator-SC, Alferon N, Crixivan, Cytovene, Cytovene-IV, Epivir, Famvir, Flumadine, Foseavir, Hivid, Intron A, Invirase, Norvir, Rebetron, Rescriptor, Retrovir, Retrovir IV, Symmetrel, Synagis, Valtrex, Videx, Viracept, Viramune, Virazole, Vistide, Zerit, Amantadine HCl, Lamiduvine, Zovirax, Dapsone, Daraprim, Flagyl 375, Flagyl, Furoxone, Mepron, Neutrexin, Cipro, Floxin, Levaquin, Mazaquin, Noroxin, Penetrex, Raxar, Trovan, Zagam, Bactrim, Bactrim DS, Pediazole, Septra, Septra DS, Co-Trimoxazole, Erythromycin/Sulfioxazole, Sulfadiazine, Sulfamethoxazole, Sulfapyridine, Sulfisoxazole, Furadantin, Macrobid, Macrodantin, Monurol, NegGram, Septra, Septra DS, Urised, Urobiotic-250, Uroqid, Vira-A, Chibroxin, Chibroxan, Blephamide, A/T/S, Benzamycin, Betadine, Cleocin T, Clindets, Emgel, Erycette, Klaron, Mycostatin, Theramycin Z, T-Stat, Terramycin, Exelderm, Fungizone, Lamisil, Loprox, Lotrimin, Lotrisone, Mentax, Monistat-Derm, Mycelex, Mycostatin, Naftin, Nizoral, Nystop, Oxistat, Selsun Rx, Spectazole, Denavir, Zovirax, Benzashave, Betadine, Betasept, Cetaphil, Clorpactin, Dapsone, Desquam-E, Desquam-X, Hibiclens, Hibistat, Impregon, MetroCream, MetroGel, Noritate, pHisoHex, Sulfacet-R, Sulfamylon, Triaz, Vanoxide-HC, Acticin, Elimite, Eurax, Lindane, Efudex, Fluoroplex, Zyvox, or Nitrofurantoin, or a pharmaceutically acceptable residue thereof.
- 43. The composition of claim 40 wherein the antibiotic is Ciprofloxacin, Levofloxacin, Ofloxacin or Sparfloxacin, or a pharmaceutically acceptable residue thereof.
- 44. A method for the treatment or prophylaxis of an infection in a host, comprising administering a therapeutic amount of the compound of any one of the preceding claims 1-38, or its pharmaceutically acceptable salt therein, which comprises an antibiotic.
- 45. A method for the treatment, prophylaxis and/or diagnosis of an infection in a host, comprising administering an effective amount of the compound of any one of the preceding claims 1-38, or its pharmaceutically acceptable salt therein, which comprises an antibiotic and/or an imaging agent, and optionally detecting the presence of the compound.
- 46. A method for the diagnosis of an infection in a host, comprising administering to the animal a detectable amount of the compound of any one of the preceding claims 28-38, or its pharmaceutically acceptable salt therein, which comprises an imaging agent and detecting the presence of the compound.
- 47. A method for the treatment or prophylaxis of an infection in a host, comprising administering a therapeutic amount of a pharmaceutical composition comprising the compound of any one of the preceding claims 1-38, which is contains at least one antibiotic, or its pharmaceutically acceptable salt therein, and a pharmaceutically acceptable carrier.
- 48. A method for the treatment, prophylaxis and/or diagnosis of an infection in a host, comprising administering an effective amount of a pharmaceutical composition comprising the compound of any one of the preceding claims 1-38, linked to at least one antibiotic and/or imaging agent, or its pharmaceutically acceptable salt therein, and a pharmaceutically acceptable carrier, and optionally detecting the presence of the compound.
- 49. A method for the diagnosis of an infection in a host, comprising administering a detectable amount of a pharmaceutical composition comprising the compound of any one of the preceding claims 28-38, linked to at least one imaging agent, or its pharmaceutically acceptable salt therein, and a pharmaceutically acceptable carrier, and detecting the presence of the compound.
- 50. The method of any one of claims 44-49 wherein the infection is an acute lower respiratory infection, lower urinary tract infection, tuberculosis, Lyme's disease, malaria, meningitis, meningitis caused by Neisseria meningitis, hepatitis, measles, neonatal tetanus, diarrheal disease, whooping cough, intestinal worm disease, sexually transmitted diseases, or any combination thereof.
Parent Case Info
[0001] This application claims priority to U.S. provisional application No. 60/208,148, filed on May 31, 2000 and U.S. provisional application No. 60/267,543, filed on Feb. 9, 2001.
Provisional Applications (2)
|
Number |
Date |
Country |
|
60208148 |
May 2000 |
US |
|
60267543 |
Feb 2001 |
US |
Patent Application
20020042394
