ES2213775T3 - Metodos de lucha contra las enfermedades infecciosas utilizando bis-benzimidazol dicationicos. - Google Patents

Metodos de lucha contra las enfermedades infecciosas utilizando bis-benzimidazol dicationicos.

Info

Publication number: ES2213775T3
Authority: ES; Spain
Prior art keywords: bis; compound; alkyl; pyridine; compounds
Prior art date: 1995-06-07
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.): Expired - Lifetime

Application number

ES96916817T

Other languages

English (en)

Spanish (es)

Inventor

Christine C. Dykstra

John R. Perfect

David W. Boykin

W. David Wilson

Richard R. Tidwell

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

University of North Carolina at Chapel Hill

Georgia State University Research Foundation Inc

Duke University

Original Assignee

University of North Carolina at Chapel Hill

Georgia State University Research Foundation Inc

Duke University

Priority date (The priority date 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 date listed.)

1995-06-07

Filing date

1996-06-03

Publication date

2004-09-01

1996-06-03 Application filed by University of North Carolina at Chapel Hill, Georgia State University Research Foundation Inc, Duke University filed Critical University of North Carolina at Chapel Hill

2004-09-01 Application granted granted Critical

2004-09-01 Publication of ES2213775T3 publication Critical patent/ES2213775T3/es

2016-06-03 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

238000000034 method Methods 0.000 title abstract description 26
208000035473 Communicable disease Diseases 0.000 title description 3
INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 title description 2
201000007336 Cryptococcosis Diseases 0.000 claims abstract description 20
238000011282 treatment Methods 0.000 claims abstract description 10
150000001875 compounds Chemical class 0.000 claims description 70
150000003839 salts Chemical class 0.000 claims description 44
-1 alkoxycycloalkoxy Chemical group 0.000 claims description 11
125000000217 alkyl group Chemical group 0.000 claims description 11
229910052739 hydrogen Inorganic materials 0.000 claims description 9
125000003118 aryl group Chemical group 0.000 claims description 8
125000004103 aminoalkyl group Chemical group 0.000 claims description 7
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 7
XEHGMWQTKPXNEZ-UHFFFAOYSA-N 2-[6-(6-carbamimidoyl-1h-benzimidazole-2-carbonyl)pyridine-2-carbonyl]-3h-benzimidazole-5-carboximidamide Chemical compound C1=C(C(N)=N)C=C2NC(C(=O)C=3C=CC=C(N=3)C(=O)C3=NC4=CC=C(C=C4N3)C(=N)N)=NC2=C1 XEHGMWQTKPXNEZ-UHFFFAOYSA-N 0.000 claims description 6
ADBIDLGZBNZQMZ-UHFFFAOYSA-N 6-(1,4,5,6-tetrahydropyrimidin-2-yl)-2-[6-[6-(1,4,5,6-tetrahydropyrimidin-2-yl)-1h-benzimidazol-2-yl]pyridin-2-yl]-1h-benzimidazole Chemical compound C1CCNC(C=2C=C3NC(=NC3=CC=2)C=2N=C(C=CC=2)C=2NC3=CC(=CC=C3N=2)C=2NCCCN=2)=N1 ADBIDLGZBNZQMZ-UHFFFAOYSA-N 0.000 claims description 6
LDEOFHIKUXEBEZ-UHFFFAOYSA-N 6-(4,5-dihydroimidazol-1-yl)-2-[6-[6-(4,5-dihydroimidazol-1-yl)-1h-benzimidazol-2-yl]pyridin-2-yl]-1h-benzimidazole Chemical compound C1=NCCN1C1=CC=C(N=C(N2)C=3N=C(C=CC=3)C=3NC4=CC(=CC=C4N=3)N3C=NCC3)C2=C1 LDEOFHIKUXEBEZ-UHFFFAOYSA-N 0.000 claims description 5
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
125000000753 cycloalkyl group Chemical group 0.000 claims description 5
239000003814 drug Substances 0.000 claims description 5
238000002360 preparation method Methods 0.000 claims description 5
238000011321 prophylaxis Methods 0.000 claims description 5
125000002877 alkyl aryl group Chemical group 0.000 claims description 4
125000002947 alkylene group Chemical group 0.000 claims description 4
125000005001 aminoaryl group Chemical group 0.000 claims description 2
125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 2
125000003710 aryl alkyl group Chemical group 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
125000005350 hydroxycycloalkyl group Chemical group 0.000 claims description 2
125000005429 oxyalkyl group Chemical group 0.000 claims description 2
125000000278 alkyl amino alkyl group Chemical group 0.000 claims 2
241000221204 Cryptococcus neoformans Species 0.000 abstract description 13
241000222122 Candida albicans Species 0.000 abstract description 7
229940095731 candida albicans Drugs 0.000 abstract description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
239000000203 mixture Substances 0.000 description 18
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
239000007787 solid Substances 0.000 description 10
238000009472 formulation Methods 0.000 description 9
201000010099 disease Diseases 0.000 description 8
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
239000002245 particle Substances 0.000 description 8
239000003981 vehicle Substances 0.000 description 8
208000030507 AIDS Diseases 0.000 description 7
208000031888 Mycoses Diseases 0.000 description 7
239000002502 liposome Substances 0.000 description 7
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
239000000243 solution Substances 0.000 description 7
206010061598 Immunodeficiency Diseases 0.000 description 6
206010017533 Fungal infection Diseases 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
238000002844 melting Methods 0.000 description 5
230000008018 melting Effects 0.000 description 5
239000008194 pharmaceutical composition Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
239000000443 aerosol Substances 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 4
239000003995 emulsifying agent Substances 0.000 description 4
208000015181 infectious disease Diseases 0.000 description 4
239000007788 liquid Substances 0.000 description 4
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 3
230000004568 DNA-binding Effects 0.000 description 3
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
238000002835 absorbance Methods 0.000 description 3
239000002253 acid Substances 0.000 description 3
229940121375 antifungal agent Drugs 0.000 description 3
150000003851 azoles Chemical class 0.000 description 3
230000027455 binding Effects 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
238000006243 chemical reaction Methods 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
230000000694 effects Effects 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
LELOWRISYMNNSU-UHFFFAOYSA-N hydrogen cyanide Chemical compound N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 3
230000000813 microbial effect Effects 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
MKVBQBLIGAFRIY-UHFFFAOYSA-N 1h-pyrrole-2,5-dicarbaldehyde Chemical compound O=CC1=CC=C(C=O)N1 MKVBQBLIGAFRIY-UHFFFAOYSA-N 0.000 description 2
XNXZZFQZGVFMAN-UHFFFAOYSA-N 4-bromo-1,2-dinitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(Br)C=C1[N+]([O-])=O XNXZZFQZGVFMAN-UHFFFAOYSA-N 0.000 description 2
WIHHVKUARKTSBU-UHFFFAOYSA-N 4-bromobenzene-1,2-diamine Chemical compound NC1=CC=C(Br)C=C1N WIHHVKUARKTSBU-UHFFFAOYSA-N 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
239000000654 additive Substances 0.000 description 2
239000003429 antifungal agent Substances 0.000 description 2
238000002815 broth microdilution Methods 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 2
230000008859 change Effects 0.000 description 2
238000004666 chemical force microscopy Methods 0.000 description 2
238000002512 chemotherapy Methods 0.000 description 2
235000012000 cholesterol Nutrition 0.000 description 2
239000000839 emulsion Substances 0.000 description 2
230000000855 fungicidal effect Effects 0.000 description 2
239000000417 fungicide Substances 0.000 description 2
230000012010 growth Effects 0.000 description 2
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 2
238000000338 in vitro Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
239000002054 inoculum Substances 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
150000002632 lipids Chemical class 0.000 description 2
238000005259 measurement Methods 0.000 description 2
LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
150000002825 nitriles Chemical class 0.000 description 2
WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 2
150000004291 polyenes Chemical class 0.000 description 2
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
239000002904 solvent Substances 0.000 description 2
239000000126 substance Substances 0.000 description 2
230000001988 toxicity Effects 0.000 description 2
231100000419 toxicity Toxicity 0.000 description 2
125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
AEQDJSLRWYMAQI-UHFFFAOYSA-N 2,3,9,10-tetramethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline Chemical compound C1CN2CC(C(=C(OC)C=C3)OC)=C3CC2C2=C1C=C(OC)C(OC)=C2 AEQDJSLRWYMAQI-UHFFFAOYSA-N 0.000 description 1
BSJFQLTXMSGMPX-UHFFFAOYSA-N 2,3-diaminobenzenecarboximidamide Chemical compound NC(=N)C1=CC=CC(N)=C1N BSJFQLTXMSGMPX-UHFFFAOYSA-N 0.000 description 1
YQQCEOMFCLGSTF-UHFFFAOYSA-N 3,4-diaminobenzenecarboximidamide Chemical compound NC(=N)C1=CC=C(N)C(N)=C1 YQQCEOMFCLGSTF-UHFFFAOYSA-N 0.000 description 1
BVMJUFXKJJPTRF-UHFFFAOYSA-N 4-(1,2,3,4-tetrahydropyrimidin-2-yl)benzene-1,2-diamine Chemical compound C1=C(N)C(N)=CC=C1C1NC=CCN1 BVMJUFXKJJPTRF-UHFFFAOYSA-N 0.000 description 1
QVZGXYWTAPUJRR-UHFFFAOYSA-N 4-(4,5-dihydro-1h-imidazol-2-yl)benzene-1,2-diamine Chemical compound C1=C(N)C(N)=CC=C1C1=NCCN1 QVZGXYWTAPUJRR-UHFFFAOYSA-N 0.000 description 1
CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
VSNQPTQMESPKQH-UHFFFAOYSA-N 6-bromo-2-[5-(6-bromo-1h-benzimidazol-2-yl)-1h-pyrrol-2-yl]-1h-benzimidazole Chemical compound C1=C(Br)C=C2NC(C3=CC=C(N3)C3=NC4=CC=C(C=C4N3)Br)=NC2=C1 VSNQPTQMESPKQH-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=C[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-KKGHZKTASA-N 0.000 description 1
BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
241000222120 Candida <Saccharomycetales> Species 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
241001337994 Cryptococcus <scale insect> Species 0.000 description 1
RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
102000004190 Enzymes Human genes 0.000 description 1
108090000790 Enzymes Proteins 0.000 description 1
PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
239000000232 Lipid Bilayer Substances 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
208000001388 Opportunistic Infections Diseases 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
239000002202 Polyethylene glycol Substances 0.000 description 1
239000012979 RPMI medium Substances 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
101710183280 Topoisomerase Proteins 0.000 description 1
102000007537 Type II DNA Topoisomerases Human genes 0.000 description 1
108010046308 Type II DNA Topoisomerases Proteins 0.000 description 1
229940022663 acetate Drugs 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
125000003277 amino group Chemical group 0.000 description 1
BIVUUOPIAYRCAP-UHFFFAOYSA-N aminoazanium;chloride Chemical class Cl.NN BIVUUOPIAYRCAP-UHFFFAOYSA-N 0.000 description 1
APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
229960003942 amphotericin b Drugs 0.000 description 1
239000003242 anti bacterial agent Substances 0.000 description 1
230000000843 anti-fungal effect Effects 0.000 description 1
230000000845 anti-microbial effect Effects 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
239000008135 aqueous vehicle Substances 0.000 description 1
235000019445 benzyl alcohol Nutrition 0.000 description 1
229960004217 benzyl alcohol Drugs 0.000 description 1
229910021538 borax Inorganic materials 0.000 description 1
244000309466 calf Species 0.000 description 1
238000000006 cell growth inhibition assay Methods 0.000 description 1
229940126214 compound 3 Drugs 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 1
125000004122 cyclic group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000004925 denaturation Methods 0.000 description 1
230000036425 denaturation Effects 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000005429 filling process Methods 0.000 description 1
238000001914 filtration Methods 0.000 description 1
XRECTZIEBJDKEO-UHFFFAOYSA-N flucytosine Chemical compound NC1=NC(=O)NC=C1F XRECTZIEBJDKEO-UHFFFAOYSA-N 0.000 description 1
229960004413 flucytosine Drugs 0.000 description 1
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
230000002538 fungal effect Effects 0.000 description 1
244000053095 fungal pathogen Species 0.000 description 1
230000004927 fusion Effects 0.000 description 1
239000011521 glass Substances 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
230000036541 health Effects 0.000 description 1
150000002391 heterocyclic compounds Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
238000000265 homogenisation Methods 0.000 description 1
230000002209 hydrophobic effect Effects 0.000 description 1
125000002636 imidazolinyl group Chemical group 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
230000002458 infectious effect Effects 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
238000007918 intramuscular administration Methods 0.000 description 1
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
229940001447 lactate Drugs 0.000 description 1
239000000787 lecithin Substances 0.000 description 1
229940067606 lecithin Drugs 0.000 description 1
235000010445 lecithin Nutrition 0.000 description 1
230000000670 limiting effect Effects 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
239000002609 medium Substances 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
229960002216 methylparaben Drugs 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
108020004707 nucleic acids Proteins 0.000 description 1
102000039446 nucleic acids Human genes 0.000 description 1
150000007523 nucleic acids Chemical class 0.000 description 1
210000000056 organ Anatomy 0.000 description 1
239000003002 pH adjusting agent Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229920001223 polyethylene glycol Polymers 0.000 description 1
108091033319 polynucleotide Proteins 0.000 description 1
102000040430 polynucleotide Human genes 0.000 description 1
239000002157 polynucleotide Substances 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
238000012545 processing Methods 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
AOHJOMMDDJHIJH-UHFFFAOYSA-N propylenediamine Chemical compound CC(N)CN AOHJOMMDDJHIJH-UHFFFAOYSA-N 0.000 description 1
229960003415 propylparaben Drugs 0.000 description 1
PMWXGSWIOOVHEQ-UHFFFAOYSA-N pyridine-2,6-dicarbaldehyde Chemical compound O=CC1=CC=CC(C=O)=N1 PMWXGSWIOOVHEQ-UHFFFAOYSA-N 0.000 description 1
230000009467 reduction Effects 0.000 description 1
230000002829 reductive effect Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
230000035945 sensitivity Effects 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
235000011083 sodium citrates Nutrition 0.000 description 1
239000000176 sodium gluconate Substances 0.000 description 1
235000012207 sodium gluconate Nutrition 0.000 description 1
229940005574 sodium gluconate Drugs 0.000 description 1
239000001540 sodium lactate Substances 0.000 description 1
229940005581 sodium lactate Drugs 0.000 description 1
235000011088 sodium lactate Nutrition 0.000 description 1
239000001488 sodium phosphate Substances 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
235000011008 sodium phosphates Nutrition 0.000 description 1
235000010339 sodium tetraborate Nutrition 0.000 description 1
238000000527 sonication Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
125000003107 substituted aryl group Chemical group 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
230000004083 survival effect Effects 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
238000012360 testing method Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000001149 thermolysis Methods 0.000 description 1
210000001541 thymus gland Anatomy 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
238000002054 transplantation Methods 0.000 description 1
BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
230000036642 wellbeing Effects 0.000 description 1

Classifications

- 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
- A61K31/425—Thiazoles
- A61K31/427—Thiazoles not condensed and containing further heterocyclic rings
- 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
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
- 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
- A61K31/42—Oxazoles
- A61K31/422—Oxazoles not condensed and containing further heterocyclic rings
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
- 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
- A61P31/10—Antimycotics

Landscapes

Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Epidemiology (AREA)
Communicable Diseases (AREA)
Oncology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)

ES96916817T 1995-06-07 1996-06-03 Metodos de lucha contra las enfermedades infecciosas utilizando bis-benzimidazol dicationicos. Expired - Lifetime ES2213775T3 (es)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US472996		1995-06-07
US08/472,996 US5643935A (en)	1995-06-07	1995-06-07	Method of combatting infectious diseases using dicationic bis-benzimidazoles

Publications (1)

Publication Number	Publication Date
ES2213775T3 true ES2213775T3 (es)	2004-09-01

Family

ID=23877744

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
ES96916817T Expired - Lifetime ES2213775T3 (es)	1995-06-07	1996-06-03	Metodos de lucha contra las enfermedades infecciosas utilizando bis-benzimidazol dicationicos.

Country Status (9)

Country	Link
US (11)	US5643935A (2)
EP (1)	EP0831832B1 (2)
JP (1)	JPH11507036A (2)
AT (1)	ATE256464T1 (2)
AU (1)	AU705261B2 (2)
CA (1)	CA2223912A1 (2)
DE (1)	DE69631134T2 (2)
ES (1)	ES2213775T3 (2)
WO (1)	WO1996040145A1 (2)

Families Citing this family (47)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5770617A (en) *	1996-03-20	1998-06-23	Rutgers, The State University Of New Jersey	Terbenzimidazoles useful as antifungal agents
US5935982A (en) *	1997-02-28	1999-08-10	The University Of North Carolina At Chapel Hill	Methods of treating retroviral infection and compounds useful therefor
US6635668B1 (en) *	1998-07-22	2003-10-21	The University Of North Carolina At Chapel Hill	Imidazoline receptor binding compounds
CA2344445A1 (en) *	1998-09-17	2000-03-23	The University Of North Carolina At Chapel Hill	Antifungal activity of dicationic molecules
EP1685836A3 (en) *	1998-09-17	2007-05-09	University Of North Carolina At Chapel Hill	Antifungal activity of dicationic molecules
EP1165096B1 (en) *	1999-03-29	2009-09-09	Shire Canada Inc.	Use of cytidine derivatives for the treatment of leukaemia
DK1231910T3 (da) *	1999-11-16	2009-08-31	Oncozyme Pharma Inc	Pentamidin til behandling af cancer
US7115665B1 (en)	2000-11-16	2006-10-03	Onocozyme Pharma, Inc.	Inhibitors of endo-exonuclease activity for treating cancer
US7156809B2 (en)	1999-12-17	2007-01-02	Q-Tec Systems Llc	Method and apparatus for health and disease management combining patient data monitoring with wireless internet connectivity
US6677377B2 (en) *	2000-06-21	2004-01-13	Georgetown University School Of Medicine	Structure based discovery of inhibitors of matriptase for the treatment of cancer and other conditions
US6569853B1 (en) *	2000-11-06	2003-05-27	Combinatorx, Incorporated	Combinations of chlorpromazine and pentamidine for the treatment of neoplastic disorders
US6706754B2 (en) *	2000-11-06	2004-03-16	The United States Of America As Represented By The Secretary Of The Army	Reversed amidines and methods of using for treating, preventing, or inhibiting leishmaniasis
MXPA04001153A (es) *	2001-08-31	2005-02-17	Neurochem Int Ltd	Derivados de amidina para tratar la amiloidosis.
AU2003302218A1 (en)	2002-05-16	2004-06-18	Genelabs Technologies, Inc	Aryl and heteroaryl compounds as antibacterial and antifungal agents
MXPA04012628A (es) *	2002-06-13	2005-03-23	Patricia Olivershaffer	DERIVADOS Y COMPUESTOS RELACIONADOS DEL áCIDO 2-UREIDO-6-HETEROARIL-3H-BENZOIMIDAZOL-4-CARBOXILICO COMO INHIBIDORES DE GIRASA Y/O TOPOISOMERASA IV PARA EL TRATAMIENTO DE INFECCIONES BACTERIALES.
US7582641B2 (en) *	2003-01-31	2009-09-01	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
AR042956A1 (es) *	2003-01-31	2005-07-13	Vertex Pharma	Inhibidores de girasa y usos de los mismos
US7618974B2 (en) *	2003-01-31	2009-11-17	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US8404852B2 (en)	2003-01-31	2013-03-26	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US7569591B2 (en) *	2003-01-31	2009-08-04	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US8193352B2 (en) *	2003-01-31	2012-06-05	Vertex Pharmaceuticals Incorporated	Gyrase inhibitors and uses thereof
US20050054708A1 (en) *	2003-07-28	2005-03-10	Nichols Matthew James	Combinations of drugs for the treatment of neoplasms
US20050080075A1 (en) *	2003-08-25	2005-04-14	Nichols M. James	Formulations, conjugates, and combinations of drugs for the treatment of neoplasms
US20050100508A1 (en) *	2003-11-12	2005-05-12	Nichols M. J.	Methods for identifying drug combinations for the treatment of proliferative diseases
US20050158320A1 (en) *	2003-11-12	2005-07-21	Nichols M. J.	Combinations for the treatment of proliferative diseases
US7262223B2 (en) *	2004-01-23	2007-08-28	Neurochem (International) Limited	Amidine derivatives for treating amyloidosis
WO2005089370A2 (en)	2004-03-16	2005-09-29	Goodis Charles J	Endodontic files and obturator devices and methods of manufacturing same
US7459457B2 (en)	2004-04-13	2008-12-02	Icagen, Inc.	Polycyclic pyridines as potassium ion channel modulators
DE102004031656A1 (de) *	2004-06-30	2006-01-19	Merck Patent Gmbh	Tetrahydrochinoline
US7817792B2 (en) *	2006-05-04	2010-10-19	Microsoft Corporation	Hyperlink-based softphone call and management
DE102007013856A1 (de)	2007-03-20	2008-09-25	Merck Patent Gmbh	Substituierte Tetrahydropyrrolochinoline
DE102007013854A1 (de)	2007-03-20	2008-09-25	Merck Patent Gmbh	Tetrahydrochinoline
DE102007013855A1 (de)	2007-03-20	2008-09-25	Merck Patent Gmbh	Substituierte Tetrahydrochinoline
EP2194981B1 (en) *	2007-10-05	2011-11-23	Université de Mons-Hainaut	Bisbenzimidazoles as antimalarial agents
US8748618B2 (en)	2009-05-13	2014-06-10	University Of Virginia Patent Foundation	Inhibitors of inv(16) leukemia
RU2625305C2 (ru)	2011-01-14	2017-07-13	Сперо Тринем, Инк.	Твердые формы ингибитора гиразы (r)-1-этил-3-[6-фтор-5[2-(1-гидрокси-1-метил-этил) пиримидин-5-ил]-7-(тетрагидрофуран-2-ил)-1н-бензимидазол-2-ил] мочевины
JP6085829B2 (ja)	2011-01-14	2017-03-01	スペロトリネム，インコーポレイテッド	ピリミジンジャイレースおよびトポイソメラーゼｉｖ阻害剤
PT2663556E (pt)	2011-01-14	2014-11-27	Vertex Pharma	Processo de fabrico de inibidores de girase e topoisomerase iv
EP2663558A1 (en)	2011-01-14	2013-11-20	Vertex Pharmaceuticals Incorporated	Solid forms of gyrase inhibitor (r)-1-ethyl-3-[5-[2-{1-hydroxy-1-methyl-ethyl}pyrimidin-5-yl]-7-(tetrahydrofuran-2-yl}-1h-benzimidazol-2-yl]urea
WO2012177707A1 (en)	2011-06-20	2012-12-27	Vertex Pharmaceuticals Incorporated	Phosphate esters of gyrase and topoisomerase inhibitors
US9018216B2 (en)	2012-07-18	2015-04-28	Vertex Pharmaceuticals Incorporated	Solid forms of (R)-2-(5-(2-(3-ethylureido)-6-fluoro-7-(tetrahydrofuran-2-yl)-1H-benzo[d]imidazol-5-yl)pyrimidin-2-yl)propan-2-yl dihydrogen phosphate and salts thereof
WO2014014845A1 (en)	2012-07-18	2014-01-23	Vertex Pharmaceuticals Incorporated	Combination therapy comprising\|1 -ethyl-3-[5-[2-{1 -hydroxy-1 -methyl-ethyl}pyrimidin-5-yl]-7-(tetra hydrofuran-2-\|yl}-1 h-benzimidazol-2-yl]urea and derivatives thereof to treat mycobacterium\|diseases
GB201506658D0 (en)	2015-04-20	2015-06-03	Cellcentric Ltd	Pharmaceutical compounds
GB201506660D0 (en)	2015-04-20	2015-06-03	Cellcentric Ltd	Pharmaceutical compounds
HK1248235A1 (zh) *	2015-05-15	2018-10-12	吉利德科学公司	具有作为吲哚胺2，3-二加氧酶抑制剂活性的苯并咪唑和咪唑并吡啶亚氨代甲酰胺化合物
EA201990395A1 (ru)	2016-07-27	2019-07-31	Юниверсити Оф Вирджиния Пэйтент Фаундейшн	Варианты комбинированной терапии для лечения рака
US20200030295A1 (en) *	2016-08-02	2020-01-30	Friedrich-Alexander-Universität Erlangen-Nürnberg	Heterocyclic diamidines

Family Cites Families (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB1542284A (en) *	1976-01-09	1979-03-14	Barcrest Ltd	Recording electrical information
ES467739A1 (es) *	1977-03-16	1979-07-01	Hoechst Ag	Procedimiento para la preparacion de compuestos de bisbenci-midazolil sustituidos
DE2839989A1 (de) *	1978-09-14	1980-04-03	Hoechst Ag	Substituierte bisbenzimidazolylverbindungen, ihre herstellung und ihre verwendung
US4963589A (en) *	1988-10-25	1990-10-16	The University Of North Carolina At Chapel Hill	Methods for treating Giardia lamblia
US4933347A (en) *	1988-10-25	1990-06-12	University Of North Carolina At Chapel Hill	Diamidines and bis(imidazolines) for the treatment of and prophylaxis against pneumocystis carinii pneumonia
US5134152A (en) *	1989-12-07	1992-07-28	Sankyo Company, Limited	Oxetane derivatives and their use as anti-fungal or fungicidal agents
FR2674246B1 (fr) *	1991-03-21	1993-07-09	Roussel Uclaf	Nouveaux derives de l'acide alpha-methylene 5-thiazolacetique, leur procede de preparation et les intermediaires de ce procede, leur application a titre de fongicides et les compositions les renfermant.
EP0508527A1 (en) *	1991-04-11	1992-10-14	UNIROYAL CHEMICAL COMPANY, Inc.	New fungicidally active pyrazole compounds
US5362910A (en) *	1991-10-08	1994-11-08	Nicca Chemical Co., Ltd.	Germicidal and fungicidal agent and a germicidal and fungicidal method
JPH05140114A (ja) *	1991-11-22	1993-06-08	Otsuka Chem Co Ltd	アゾール−１−カルボン酸エステル誘導体及び殺菌剤
US5428051A (en) *	1992-10-13	1995-06-27	University Of North Carolina	Methods of combating pneumocystis carinii pneumonia and compounds useful therefor
US5667975A (en) *	1994-05-06	1997-09-16	The University Of North Carolina	Method of fluorescent detection of nucleic acids and cytoskeleton elements using bis-dicationic aryl furans

1995
- 1995-06-07 US US08/472,996 patent/US5643935A/en not_active Expired - Fee Related
1996
- 1996-05-01 US US08/641,510 patent/US5639755A/en not_active Expired - Fee Related
- 1996-06-03 WO PCT/US1996/008084 patent/WO1996040145A1/en not_active Ceased
- 1996-06-03 ES ES96916817T patent/ES2213775T3/es not_active Expired - Lifetime
- 1996-06-03 CA CA002223912A patent/CA2223912A1/en not_active Abandoned
- 1996-06-03 JP JP9500868A patent/JPH11507036A/ja not_active Ceased
- 1996-06-03 AU AU59566/96A patent/AU705261B2/en not_active Ceased
- 1996-06-03 EP EP96916817A patent/EP0831832B1/en not_active Expired - Lifetime
- 1996-06-03 AT AT96916817T patent/ATE256464T1/de not_active IP Right Cessation
- 1996-06-03 DE DE69631134T patent/DE69631134T2/de not_active Expired - Fee Related
1997
- 1997-05-29 US US08/865,425 patent/US5817687A/en not_active Expired - Fee Related
- 1997-05-29 US US08/865,427 patent/US5817686A/en not_active Expired - Fee Related
- 1997-05-29 US US08/865,424 patent/US5792782A/en not_active Expired - Lifetime
1998
- 1998-08-07 US US09/130,496 patent/US5939440A/en not_active Expired - Fee Related
- 1998-09-01 US US09/145,367 patent/US5972969A/en not_active Expired - Lifetime
- 1998-09-01 US US09/145,368 patent/US6017941A/en not_active Expired - Lifetime
1999
- 1999-07-13 US US09/352,391 patent/US6046226A/en not_active Expired - Lifetime
2000
- 2000-01-04 US US09/477,386 patent/US6156779A/en not_active Expired - Lifetime
- 2000-04-06 US US09/544,643 patent/US6294565B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
DE69631134D1 (de)	2004-01-29
US6294565B1 (en)	2001-09-25
US5792782A (en)	1998-08-11
US5972969A (en)	1999-10-26
US6017941A (en)	2000-01-25
AU5956696A (en)	1996-12-30
EP0831832B1 (en)	2003-12-17
WO1996040145A1 (en)	1996-12-19
JPH11507036A (ja)	1999-06-22
US5639755A (en)	1997-06-17
US6046226A (en)	2000-04-04
US6156779A (en)	2000-12-05
US5817686A (en)	1998-10-06
AU705261B2 (en)	1999-05-20
ATE256464T1 (de)	2004-01-15
DE69631134T2 (de)	2004-09-02
US5643935A (en)	1997-07-01
CA2223912A1 (en)	1996-12-19
US5817687A (en)	1998-10-06
US5939440A (en)	1999-08-17
EP0831832A4 (en)	1999-07-07
EP0831832A1 (en)	1998-04-01

Publication	Publication Date	Title
EP0831832B1 (en)	2003-12-17	Methods of combatting infectious diseases using dicationic bis-benzimidazoles
US5627184A (en)	1997-05-06	Methods of treating Giardia lamblia
EP1143959B1 (en)	2006-11-02	Antifungal activity of dicationic molecules
KR102232625B1 (ko)	2021-03-25	폐 병태의 치료를 위한 고침투 전구약물 조성물 및 그의 약제학적 조성물
AU2021201251B2 (en)	2022-07-21	Antimicrobial compounds, compositions, and uses thereof
JP2011500577A (ja)	2011-01-06	バルサルタンの医薬製剤
ES2236734T3 (es)	2005-07-16	Metodos para combatir la neumonia pneumocystis carinii y compuestos utiles para ello.
JP3306830B2 (ja)	2002-07-24	レトロウイルスインテグラーゼの阻害剤
HUP0203121A2 (hu)	2003-01-28	Szubsztituált benzimidazolokat tartalmazó gyógyszerkészítmény és alkalmazása
JP4823894B2 (ja)	2011-11-24	新規水溶性プロドラッグ
US20240002332A1 (en)	2024-01-04	Small Molecule Inhibitors of SARS-CoV-2 Infections
ES3031785T3 (en)	2025-07-11	Triamterene or nolatrexed for use in the treatment of phenylketonuria
KR20060004959A (ko)	2006-01-16	신장 기능 저하를 갖는 개별 대상자의 이뇨 작용 개선 방법
EP0792271B1 (en)	2002-02-27	Furan derivatives for inhibiting pneumocystis carinii pneumonia, giardia lamblia and cryptosporidium parvum
ES2211958T3 (es)	2004-07-16	Carbazoles para tratar infecciones microbianas.
US12280038B2 (en)	2025-04-22	L-pag derivatives for treatment of sleep disordered breathing (SDB)
KR20000035861A (ko)	2000-06-26	Ａｉｄｓ 치료용 약제를 제조하기 위한 ｐｋｃ 억제제의 사용 방법
US20070281947A1 (en)	2007-12-06	Diarylmethylpiperazines As Prophylactic Or Therapeutic Agents For Viral Myocarditis
US20030216324A1 (en)	2003-11-20	Airway mucus secretion inhibitors
KR20000035863A (ko)	2000-06-26	Ｈｉｖ 감염과 관련된 중추 신경계 질환 치료용 약제를 제조하기 위해 ｐｋｃ의 억제제를 사용하는 방법