CA2344445A1 - Antifungal activity of dicationic molecules - Google Patents
Antifungal activity of dicationic molecules Download PDFInfo
- Publication number
- CA2344445A1 CA2344445A1 CA002344445A CA2344445A CA2344445A1 CA 2344445 A1 CA2344445 A1 CA 2344445A1 CA 002344445 A CA002344445 A CA 002344445A CA 2344445 A CA2344445 A CA 2344445A CA 2344445 A1 CA2344445 A1 CA 2344445A1
- Authority
- CA
- Canada
- Prior art keywords
- aryl
- loweralkyl
- group
- alkoxyalkyl
- hydroxyalkyl
- 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.)
- Abandoned
Links
- 230000000843 anti-fungal effect Effects 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 105
- 238000000034 method Methods 0.000 claims abstract description 84
- 206010017533 Fungal infection Diseases 0.000 claims abstract description 14
- 208000031888 Mycoses Diseases 0.000 claims abstract description 14
- 241000222122 Candida albicans Species 0.000 claims abstract description 13
- 241000221204 Cryptococcus neoformans Species 0.000 claims abstract description 9
- 201000007336 Cryptococcosis Diseases 0.000 claims abstract description 5
- 241000427940 Fusarium solani Species 0.000 claims abstract description 5
- 229940095731 candida albicans Drugs 0.000 claims abstract description 5
- 241001225321 Aspergillus fumigatus Species 0.000 claims abstract description 3
- 229940091771 aspergillus fumigatus Drugs 0.000 claims abstract description 3
- -1 loweralkyl Chemical group 0.000 claims description 117
- 125000003118 aryl group Chemical group 0.000 claims description 110
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 84
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 84
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 82
- 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 77
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 75
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 73
- 125000003282 alkyl amino group Chemical group 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 41
- 125000005350 hydroxycycloalkyl group Chemical group 0.000 claims description 40
- 125000002947 alkylene group Chemical group 0.000 claims description 34
- 125000005429 oxyalkyl group Chemical group 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 11
- 125000003107 substituted aryl group Chemical group 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 239000008194 pharmaceutical composition Substances 0.000 claims description 9
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 125000005001 aminoaryl group Chemical group 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 230000002538 fungal effect Effects 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 45
- 125000004171 alkoxy aryl group Chemical group 0.000 claims 4
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- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 72
- 239000007787 solid Substances 0.000 description 44
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 37
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 26
- 238000001819 mass spectrum Methods 0.000 description 25
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- 230000000704 physical effect Effects 0.000 description 18
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- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 13
- 239000012458 free base Substances 0.000 description 12
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- 125000000217 alkyl group Chemical group 0.000 description 11
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 11
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- 229940121375 antifungal agent Drugs 0.000 description 7
- RFHAOTPXVQNOHP-UHFFFAOYSA-N fluconazole Chemical compound C1=NC=NN1CC(C=1C(=CC(F)=CC=1)F)(O)CN1C=NC=N1 RFHAOTPXVQNOHP-UHFFFAOYSA-N 0.000 description 7
- 229960004884 fluconazole Drugs 0.000 description 7
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- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 241000222120 Candida <Saccharomycetales> Species 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 6
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- 238000002474 experimental method Methods 0.000 description 6
- 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 5
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- LFDGRWDETVOGDT-UHFFFAOYSA-N 1h-pyrrole;hydrochloride Chemical compound Cl.C=1C=CNC=1 LFDGRWDETVOGDT-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 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 4
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- 238000002827 antifungal susceptibility testing Methods 0.000 description 4
- 238000012512 characterization method Methods 0.000 description 4
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- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- CEIPQQODRKXDSB-UHFFFAOYSA-N ethyl 3-(6-hydroxynaphthalen-2-yl)-1H-indazole-5-carboximidate dihydrochloride Chemical compound Cl.Cl.C1=C(O)C=CC2=CC(C3=NNC4=CC=C(C=C43)C(=N)OCC)=CC=C21 CEIPQQODRKXDSB-UHFFFAOYSA-N 0.000 description 4
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- IDSXLJLXYMLSJM-UHFFFAOYSA-N morpholine;propane-1-sulfonic acid Chemical compound C1COCCN1.CCCS(O)(=O)=O IDSXLJLXYMLSJM-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
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- 229910052623 talc Inorganic materials 0.000 description 4
- PXJJKVNIMAZHCB-UHFFFAOYSA-N 2,5-diformylfuran Chemical compound O=CC1=CC=C(C=O)O1 PXJJKVNIMAZHCB-UHFFFAOYSA-N 0.000 description 3
- CETXOEGRUBXUAL-UHFFFAOYSA-N 3-(hydroxymethyl)furan-2-carbaldehyde Chemical compound OCC=1C=COC=1C=O CETXOEGRUBXUAL-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
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- 241000123365 Cryptococcus neoformans var. neoformans Species 0.000 description 3
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
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- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 3
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- MTNDZQHUAFNZQY-UHFFFAOYSA-N imidazoline Chemical compound C1CN=CN1 MTNDZQHUAFNZQY-UHFFFAOYSA-N 0.000 description 3
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- ABJSOROVZZKJGI-OCYUSGCXSA-N (1r,2r,4r)-2-(4-bromophenyl)-n-[(4-chlorophenyl)-(2-fluoropyridin-4-yl)methyl]-4-morpholin-4-ylcyclohexane-1-carboxamide Chemical compound C1=NC(F)=CC(C(NC(=O)[C@H]2[C@@H](C[C@@H](CC2)N2CCOCC2)C=2C=CC(Br)=CC=2)C=2C=CC(Cl)=CC=2)=C1 ABJSOROVZZKJGI-OCYUSGCXSA-N 0.000 description 2
- IUSARDYWEPUTPN-OZBXUNDUSA-N (2r)-n-[(2s,3r)-4-[[(4s)-6-(2,2-dimethylpropyl)spiro[3,4-dihydropyrano[2,3-b]pyridine-2,1'-cyclobutane]-4-yl]amino]-3-hydroxy-1-[3-(1,3-thiazol-2-yl)phenyl]butan-2-yl]-2-methoxypropanamide Chemical compound C([C@H](NC(=O)[C@@H](C)OC)[C@H](O)CN[C@@H]1C2=CC(CC(C)(C)C)=CN=C2OC2(CCC2)C1)C(C=1)=CC=CC=1C1=NC=CS1 IUSARDYWEPUTPN-OZBXUNDUSA-N 0.000 description 2
- STBLNCCBQMHSRC-BATDWUPUSA-N (2s)-n-[(3s,4s)-5-acetyl-7-cyano-4-methyl-1-[(2-methylnaphthalen-1-yl)methyl]-2-oxo-3,4-dihydro-1,5-benzodiazepin-3-yl]-2-(methylamino)propanamide Chemical compound O=C1[C@@H](NC(=O)[C@H](C)NC)[C@H](C)N(C(C)=O)C2=CC(C#N)=CC=C2N1CC1=C(C)C=CC2=CC=CC=C12 STBLNCCBQMHSRC-BATDWUPUSA-N 0.000 description 2
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- 208000030304 gastrointestinal bleeding Diseases 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
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- KQDJZZWCYTXUDE-UHFFFAOYSA-N hydron;thiophene;chloride Chemical compound Cl.C=1C=CSC=1 KQDJZZWCYTXUDE-UHFFFAOYSA-N 0.000 description 1
- 230000002209 hydrophobic effect Effects 0.000 description 1
- 230000001506 immunosuppresive effect Effects 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 1
- 229960004130 itraconazole Drugs 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
- 239000012528 membrane Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- YCJZWBZJSYLMPB-UHFFFAOYSA-N n-(2-chloropyrimidin-4-yl)-2,5-dimethyl-1-phenylimidazole-4-carboxamide Chemical compound CC=1N(C=2C=CC=CC=2)C(C)=NC=1C(=O)NC1=CC=NC(Cl)=N1 YCJZWBZJSYLMPB-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229960000988 nystatin Drugs 0.000 description 1
- VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 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/CC/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)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
- XULSCZPZVQIMFM-IPZQJPLYSA-N odevixibat Chemical compound C12=CC(SC)=C(OCC(=O)N[C@@H](C(=O)N[C@@H](CC)C(O)=O)C=3C=CC(O)=CC=3)C=C2S(=O)(=O)NC(CCCC)(CCCC)CN1C1=CC=CC=C1 XULSCZPZVQIMFM-IPZQJPLYSA-N 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 244000052769 pathogen Species 0.000 description 1
- XDRYMKDFEDOLFX-UHFFFAOYSA-N pentamidine Chemical compound C1=CC(C(=N)N)=CC=C1OCCCCCOC1=CC=C(C(N)=N)C=C1 XDRYMKDFEDOLFX-UHFFFAOYSA-N 0.000 description 1
- 229960004448 pentamidine Drugs 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 150000005353 phenylfurans Chemical class 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
- 125000001095 phosphatidyl group Chemical group 0.000 description 1
- WTJKGGKOPKCXLL-RRHRGVEJSA-N phosphatidylcholine Chemical group CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCCC=CCCCCCCCC WTJKGGKOPKCXLL-RRHRGVEJSA-N 0.000 description 1
- 150000004291 polyenes Chemical class 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 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
- 229960003415 propylparaben Drugs 0.000 description 1
- 239000011541 reaction mixture Substances 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
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 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
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 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
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000028070 sporulation Effects 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
- 239000011550 stock solution Substances 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002194 synthesizing 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
- 238000001149 thermolysis Methods 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- OTMRXENQDSQACG-UHFFFAOYSA-N thiophene-2,5-dicarbaldehyde Chemical compound O=CC1=CC=C(C=O)S1 OTMRXENQDSQACG-UHFFFAOYSA-N 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 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
- A61K31/4164—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
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
-
- 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)
- 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)
- Veterinary Medicine (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)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Peptides Or Proteins (AREA)
- Furan Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US10092898P | 1998-09-17 | 1998-09-17 | |
| US60/100,928 | 1998-09-17 | ||
| PCT/US1999/021383 WO2000015212A2 (en) | 1998-09-17 | 1999-09-15 | Antifungal activity of dicationic molecules |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2344445A1 true CA2344445A1 (en) | 2000-03-23 |
Family
ID=22282251
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002344445A Abandoned CA2344445A1 (en) | 1998-09-17 | 1999-09-15 | Antifungal activity of dicationic molecules |
Country Status (9)
| Country | Link |
|---|---|
| US (1) | US6326395B1 (enExample) |
| EP (1) | EP1143959B1 (enExample) |
| JP (1) | JP2002524503A (enExample) |
| AT (1) | ATE344028T1 (enExample) |
| AU (2) | AU770656B2 (enExample) |
| CA (1) | CA2344445A1 (enExample) |
| DE (1) | DE69933890T2 (enExample) |
| ES (1) | ES2275362T3 (enExample) |
| WO (1) | WO2000015212A2 (enExample) |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MXPA02005937A (es) * | 1999-12-20 | 2004-08-12 | Univ North Carolina | Compuestos de diamina como aglutinantes de surco menor. |
| US6569853B1 (en) * | 2000-11-06 | 2003-05-27 | Combinatorx, Incorporated | Combinations of chlorpromazine and pentamidine for the treatment of neoplastic disorders |
| MXPA04001153A (es) * | 2001-08-31 | 2005-02-17 | Neurochem Int Ltd | Derivados de amidina para tratar la amiloidosis. |
| WO2004047724A2 (en) | 2002-05-16 | 2004-06-10 | Genelabs Technologies, Inc | Aryl and heteroaryl compounds as antibacterial and antifungal agents |
| CA2504742A1 (en) * | 2002-11-27 | 2004-06-17 | University Of North Carolina At Chapel Hill | Process for synthesis bis-aryl diamidoxime compounds |
| US20050054708A1 (en) * | 2003-07-28 | 2005-03-10 | Nichols Matthew James | Combinations of drugs for the treatment of neoplasms |
| WO2005020913A2 (en) * | 2003-08-25 | 2005-03-10 | Combinatorx, Incorporated | 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 |
| CA2549736A1 (en) * | 2003-12-05 | 2005-06-23 | The University Of North Carolina At Chapel Hill | Cationic substituted benzofurans as antimicrobial agents |
| US7262223B2 (en) * | 2004-01-23 | 2007-08-28 | Neurochem (International) Limited | Amidine derivatives for treating amyloidosis |
| WO2005086754A2 (en) * | 2004-03-08 | 2005-09-22 | Georgia State University Research Foundation, Inc. | Dicationic compounds for activity against trichomonas vaginalis |
| US7994225B2 (en) * | 2004-03-17 | 2011-08-09 | Rempex Pharmaceuticals, Inc. | Bacterial efflux pump inhibitors for the treatment of ophthalmic and otic infections |
| WO2005089738A2 (en) * | 2004-03-17 | 2005-09-29 | Mpex Pharmaceuticals, Inc. | Use and administration of bacterial efflux pump inhibitors |
| AU2005233632A1 (en) | 2004-04-13 | 2005-10-27 | Icagen, Inc. | Polycyclic pyridines as potassium ion channel modulators |
| DE102004031656A1 (de) * | 2004-06-30 | 2006-01-19 | Merck Patent Gmbh | Tetrahydrochinoline |
| GB0619325D0 (en) * | 2006-09-30 | 2006-11-08 | Univ Strathclyde | New compounds |
| 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 |
| US20100120694A1 (en) | 2008-06-04 | 2010-05-13 | Synergy Pharmaceuticals, Inc. | Agonists of Guanylate Cyclase Useful for the Treatment of Gastrointestinal Disorders, Inflammation, Cancer and Other Disorders |
| EP2194981B1 (en) * | 2007-10-05 | 2011-11-23 | Université de Mons-Hainaut | Bisbenzimidazoles as antimalarial agents |
| WO2009084544A1 (ja) * | 2007-12-27 | 2009-07-09 | Idemitsu Kosan Co., Ltd. | 含窒素複素環誘導体及びそれを用いた有機エレクトロルミネッセンス素子 |
| US9126025B2 (en) * | 2008-05-01 | 2015-09-08 | Bayer Intellectual Property Gmbh | Method of coating a folded catheter balloon |
| US11141752B2 (en) | 2012-12-27 | 2021-10-12 | Kateeva, Inc. | Techniques for arrayed printing of a permanent layer with improved speed and accuracy |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2122208A1 (en) * | 1971-05-05 | 1972-11-23 | Farbwerke Hoechst AG, vormals Meister Lucius & Brüning, 6000 Frankfurt | Diamidino-benzimidazole derivs - with fungistatic activity |
| JPS51110531A (en) * | 1975-03-26 | 1976-09-30 | Eisai Co Ltd | Amijinokagobutsuno seizoho |
| JPS5922697B2 (ja) * | 1976-01-13 | 1984-05-28 | エーザイ株式会社 | ビス−（メタ−アミジノフエノキシ）−化合物 |
| DE2833135A1 (de) * | 1978-07-28 | 1980-02-07 | Henkel Kgaa | Verwendung von substituierten oligocarbamidinen als mikrobistatika sowie diese enthaltende antimikrobielle mittel |
| US4397863A (en) | 1980-08-26 | 1983-08-09 | Research Triangle Institute | Inhibition of respiratory syncytial virus-induced cell fusion by amidino compounds |
| US4324794A (en) | 1980-08-26 | 1982-04-13 | Research Triangle Institute | Inhibition of respiratory syncytial virus-induced cell fusion by amidino compounds |
| US4619942A (en) | 1982-04-08 | 1986-10-28 | University Of North Carolina | Inhibition of Respiratory Syncytial virus-induced cell fusion by amidino compounds |
| US4940723A (en) | 1988-10-20 | 1990-07-10 | University Of North Carolina, Chapel Hill | Use of bis-(5-amidino-2-benzimidazolyl) methane (BABIM) to treat arthritis |
| 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 |
| US5202320A (en) | 1989-04-06 | 1993-04-13 | Tidwell Richard R | Method for treating leishmaniasis |
| US5206236A (en) | 1989-04-06 | 1993-04-27 | Tidwell Richard R | Method for the treatment of malaria |
| US5428051A (en) | 1992-10-13 | 1995-06-27 | University Of North Carolina | Methods of combating pneumocystis carinii pneumonia and compounds useful therefor |
| US5723288A (en) | 1994-05-06 | 1998-03-03 | The University Of North Carolina At Chapel Hill | Method of fluorescent detection of nucleic acids and cytoskeleton elements using bis-dicationic aryl furans, and kits 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 |
| US5602172A (en) | 1994-05-06 | 1997-02-11 | The University Of North Carolina At Chapel Hill | Methods of inhibiting Pneumocystis carinii pneumonia, Giardia lamblia, and Cryptosporidium and compounds useful therefor |
| US5521189A (en) | 1994-05-06 | 1996-05-28 | The University Of Nc At Ch | Methods of treating pneumocystis carinii pneumonia |
| US5643935A (en) * | 1995-06-07 | 1997-07-01 | The University Of North Carolina At Chapel Hill | Method of combatting infectious diseases using dicationic bis-benzimidazoles |
| US5668167A (en) | 1995-06-07 | 1997-09-16 | Duke University | Methods of treating microbial infections |
| US5723495A (en) | 1995-11-16 | 1998-03-03 | The University Of North Carolina At Chapel Hill | Benzamidoxime prodrugs as antipneumocystic agents |
-
1999
- 1999-09-15 US US09/396,836 patent/US6326395B1/en not_active Expired - Lifetime
- 1999-09-15 WO PCT/US1999/021383 patent/WO2000015212A2/en not_active Ceased
- 1999-09-15 AT AT99969025T patent/ATE344028T1/de not_active IP Right Cessation
- 1999-09-15 AU AU60450/99A patent/AU770656B2/en not_active Ceased
- 1999-09-15 CA CA002344445A patent/CA2344445A1/en not_active Abandoned
- 1999-09-15 DE DE69933890T patent/DE69933890T2/de not_active Expired - Fee Related
- 1999-09-15 ES ES99969025T patent/ES2275362T3/es not_active Expired - Lifetime
- 1999-09-15 JP JP2000569796A patent/JP2002524503A/ja not_active Withdrawn
- 1999-09-15 EP EP99969025A patent/EP1143959B1/en not_active Expired - Lifetime
-
2004
- 2004-05-26 AU AU2004202311A patent/AU2004202311A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| EP1143959A2 (en) | 2001-10-17 |
| AU770656B2 (en) | 2004-02-26 |
| DE69933890T2 (de) | 2007-03-15 |
| ATE344028T1 (de) | 2006-11-15 |
| AU2004202311A1 (en) | 2004-06-24 |
| WO2000015212A2 (en) | 2000-03-23 |
| US6326395B1 (en) | 2001-12-04 |
| JP2002524503A (ja) | 2002-08-06 |
| ES2275362T3 (es) | 2007-06-01 |
| DE69933890D1 (de) | 2006-12-14 |
| EP1143959B1 (en) | 2006-11-02 |
| AU6045099A (en) | 2000-04-03 |
| WO2000015212A3 (en) | 2001-08-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |