Title:
ANTIFUNGAL ACTIVITY OF DICATIONIC MOLECULES
Document Type and Number:
WIPO Patent Application WO2000015212
Kind Code:
A3
Abstract:
Methods of treating fungal infections comprise administering a therapeutically effective amount of a compound described by Formulas (I-VI). Examples of fungal infections include Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus, Fusarium solani, and combinations thereof.
Inventors:
TIDWELL RICHARD R (US)
BOYKIN DAVID W (US)
PERFECT JOHN R (US)
BOYKIN DAVID W (US)
PERFECT JOHN R (US)
Application Number:
PCT/US1999/021383
Publication Date:
August 16, 2001
Filing Date:
September 15, 1999
Export Citation:
Assignee:
UNIV NORTH CAROLINA (US)
UNIV GEORGIA STATE RES FOUND (US)
UNIV DUKE (US)
TIDWELL RICHARD R (US)
BOYKIN DAVID W (US)
PERFECT JOHN R (US)
UNIV GEORGIA STATE RES FOUND (US)
UNIV DUKE (US)
TIDWELL RICHARD R (US)
BOYKIN DAVID W (US)
PERFECT JOHN R (US)
International Classes:
A61K31/00; A61K31/155; A61K31/341; A61K31/343; A61K31/4184; C07D235/20; A61K31/4427; A61K31/443; A61K31/4433; A61K31/4439; A61K31/5355; A61K31/5377; A61P31/10; C07D307/14; C07D307/18; C07D307/81; C07D401/14; C07D403/10; C07D403/14; C07D405/14; C07D409/14; (IPC1-7): A61K31/341; A61P31/10; A61K31/4184; A61K31/5377; A61K31/4439
Domestic Patent References:
| WO1996040145A1 | 1996-12-19 |
Foreign References:
| DE2122208A1 | 1972-11-23 | |||
| DE2833135A1 | 1980-02-07 | |||
| US4034010A | 1977-07-05 | |||
| US5602172A | 1997-02-11 | |||
| US5643935A | 1997-07-01 |
Other References:
DEL POETA, M. ET AL: "In vitro antifungal activities of a series of dication-substituted carbazoles, furans and benzimidazoles", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 42, no. 10, October 1998 (1998-10-01), pages 2503 - 2510, XP000920943
DEL POETA, M. ET AL: "In-vitro activity of dicationic aromatic compounds and fluconazole against Cryptococcus neoformans and Candida spp.", JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, vol. 44, no. 2, August 1999 (1999-08-01), pages 223 - 228, XP000090923
DEL POETA, M. ET AL: "Structure-in vitro activity relationships of pentamidine analogues and dication-substituted bis-benzimidazoles as new antifungal agents", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 42, no. 10, October 1998 (1998-10-01), pages 2495 - 2502, XP000920922
ANNÉ, J. ET AL: "Antifungal and antibacterial activities of diarylamidine derivatives", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 18, no. 2, 1980, pages 231 - 239, XP000886495
HILDEBRANDT, E. ET AL: "Identification and characterization of an endo/exonuclease in Pneumocystis carinii that is inhibited by dicationic diarylfurans with efficacy against Pneumocystis pneumonia", THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, vol. 45, no. 1, January 1998 (1998-01-01) - February 1998 (1998-02-01), pages 112 - 121, XP002142273
HOPKINS, K.T. ET AL: "Extended aromatic furan amidino derivaives as anti-Pneumocystis carinii agents", JOURNAL OF MEDICINAL CHEMISTRY, vol. 41, no. 20, 1998, pages 3872 - 3878, XP000914716
BERGER, B.J. ET AL: "Hydroxylation of pentamidine by rat liver microsomes", THE JOURNAL OF PHARMACOLOGICAL AND EXPERIMENTAL THERAPEUTICS, vol. 256, 1991, pages 883 - 889, XP000921003
LI, KE ET AL: "Design and analysis of organic cations that inhibit interactions of the HIV-1 Rev protein with RRE RNA", STRUCT., MOTION, INTERACT. EXPRESSION BIOL. MACROMOL., PROC. CONVERSATION DISCIP. BIOMOL. STEREODYN., 10TH, 1998, 2,, 137-145, XP000921396
DATABASE WPI Week 7646, Derwent World Patents Index; AN 1976-85945X, XP002154138
DONKOR, I.O. ET AL: "Antimicrobial activity of geometric isomers of butamidine and related compounds", PHARMACEUTICAL RESEARCH, vol. 13, no. 9, 1996, pages S141, XP000972148
ST-GERMAIN, G.: "Effects of pentamidine alone and in combination with ketoconazole or itraconazole on the growth of Candida albicans", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 34, no. 12, 1990, pages 2304 - 2306, XP000961099
BARCHIESI, F. ET AL: "Effect of pentamidine on the growth of Cryptococcus neoformans", JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, vol. 33, no. 6, 1994, pages 1229 - 1232, XP000961082
DAS, B.P. ET AL: "Synthesis and antiprotozoal activity of 2,5-Bis(4-guanylphenyl)furans", JOURNAL OF MEDICINAL CHEMISTRY, vol. 20, no. 4, 1977, pages 531 - 536, XP000605199
BOYKIN, D.W. ET AL: "Anti-Pneumocystis activity of bis-amidoximes and bis-O-alkylamidoxies prodrugs", BIORGANIC AND MEDICINAL CHEMISTRY LETTERS, vol. 6, no. 24, 1996, pages 3017 - 3020, XP002142274
TRENT, J.O. ET AL: "Targeting the minor groove of DNA: Crystal structures of two complexes between furan derivatives of Berenil and the DNA dodecamer", JOURNAL OF MEDICINAL CHEMISTRY, vol. 39, 1996, pages 4554 - 4562, XP000914678
BOYKIN, D.W. ET AL: "2,5-Bis(4-(N-alkylamidino)phenyl)furans as anti-Pneumocystis carinii agents", JOURNAL OF MEDICINAL CHEMISTRY, vol. 41, 1998, pages 124 - 129, XP000914677
TIDWELL, R.R. ET AL: "Analogues of 1,5-Bis(4-amidinophenoxy)pentane (Pentamidine) in the treatment of experimental Pneumocystis carinii pneumonia", THE JOURNAL OF MEDICINAL CHEMISTRY, vol. 33, no. 4, 1990, pages 1252 - 1257, XP000644781
JONES, S.K. ET AL: "Novel pentamidine analogs in the treatment of experimental Pneumocystis carinii pneumonia", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 34, no. 6, 1990, pages 1026 - 1030, XP000921002
TIDWELL, R.R. ET AL: "Diarylamidine derivatives with one or both of the aryl moieties consisting of an indole or indole-like ring. Inhibitors of arginine-specific esteroproteases", JOURNAL OF MEDICINAL CHEMISTRY, vol. 21, no. 7, 1978, pages 613 - 623, XP000573913
FAIRLEY, T.A. ET AL: "Structure, DNA minor groove binding and base pair specificity of alkyl- and aryl- linked bis(amidinobenzimidazoles) and bis(amidinoindoles)", JOURNAL OF MEDICINAL CHEMISTRY, vol. 36, no. 12, 1993, pages 1746 - 1753, XP002067234
BELL, C.A. ET AL: "Structure-activity studies of dicationically substituted bis-benzimidazoles against Giardia lamblia: Correlation of antigiardial activity with DNA binding affinity and Giardial topoisomerase II inhibition", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 37, no. 12, 1993, pages 2668 - 2673, XP000972059
DEL POETA, M. ET AL: "In-vitro activity of dicationic aromatic compounds and fluconazole against Cryptococcus neoformans and Candida spp.", JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, vol. 44, no. 2, August 1999 (1999-08-01), pages 223 - 228, XP000090923
DEL POETA, M. ET AL: "Structure-in vitro activity relationships of pentamidine analogues and dication-substituted bis-benzimidazoles as new antifungal agents", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 42, no. 10, October 1998 (1998-10-01), pages 2495 - 2502, XP000920922
ANNÉ, J. ET AL: "Antifungal and antibacterial activities of diarylamidine derivatives", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 18, no. 2, 1980, pages 231 - 239, XP000886495
HILDEBRANDT, E. ET AL: "Identification and characterization of an endo/exonuclease in Pneumocystis carinii that is inhibited by dicationic diarylfurans with efficacy against Pneumocystis pneumonia", THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, vol. 45, no. 1, January 1998 (1998-01-01) - February 1998 (1998-02-01), pages 112 - 121, XP002142273
HOPKINS, K.T. ET AL: "Extended aromatic furan amidino derivaives as anti-Pneumocystis carinii agents", JOURNAL OF MEDICINAL CHEMISTRY, vol. 41, no. 20, 1998, pages 3872 - 3878, XP000914716
BERGER, B.J. ET AL: "Hydroxylation of pentamidine by rat liver microsomes", THE JOURNAL OF PHARMACOLOGICAL AND EXPERIMENTAL THERAPEUTICS, vol. 256, 1991, pages 883 - 889, XP000921003
LI, KE ET AL: "Design and analysis of organic cations that inhibit interactions of the HIV-1 Rev protein with RRE RNA", STRUCT., MOTION, INTERACT. EXPRESSION BIOL. MACROMOL., PROC. CONVERSATION DISCIP. BIOMOL. STEREODYN., 10TH, 1998, 2,, 137-145, XP000921396
DATABASE WPI Week 7646, Derwent World Patents Index; AN 1976-85945X, XP002154138
DONKOR, I.O. ET AL: "Antimicrobial activity of geometric isomers of butamidine and related compounds", PHARMACEUTICAL RESEARCH, vol. 13, no. 9, 1996, pages S141, XP000972148
ST-GERMAIN, G.: "Effects of pentamidine alone and in combination with ketoconazole or itraconazole on the growth of Candida albicans", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 34, no. 12, 1990, pages 2304 - 2306, XP000961099
BARCHIESI, F. ET AL: "Effect of pentamidine on the growth of Cryptococcus neoformans", JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, vol. 33, no. 6, 1994, pages 1229 - 1232, XP000961082
DAS, B.P. ET AL: "Synthesis and antiprotozoal activity of 2,5-Bis(4-guanylphenyl)furans", JOURNAL OF MEDICINAL CHEMISTRY, vol. 20, no. 4, 1977, pages 531 - 536, XP000605199
BOYKIN, D.W. ET AL: "Anti-Pneumocystis activity of bis-amidoximes and bis-O-alkylamidoxies prodrugs", BIORGANIC AND MEDICINAL CHEMISTRY LETTERS, vol. 6, no. 24, 1996, pages 3017 - 3020, XP002142274
TRENT, J.O. ET AL: "Targeting the minor groove of DNA: Crystal structures of two complexes between furan derivatives of Berenil and the DNA dodecamer", JOURNAL OF MEDICINAL CHEMISTRY, vol. 39, 1996, pages 4554 - 4562, XP000914678
BOYKIN, D.W. ET AL: "2,5-Bis(4-(N-alkylamidino)phenyl)furans as anti-Pneumocystis carinii agents", JOURNAL OF MEDICINAL CHEMISTRY, vol. 41, 1998, pages 124 - 129, XP000914677
TIDWELL, R.R. ET AL: "Analogues of 1,5-Bis(4-amidinophenoxy)pentane (Pentamidine) in the treatment of experimental Pneumocystis carinii pneumonia", THE JOURNAL OF MEDICINAL CHEMISTRY, vol. 33, no. 4, 1990, pages 1252 - 1257, XP000644781
JONES, S.K. ET AL: "Novel pentamidine analogs in the treatment of experimental Pneumocystis carinii pneumonia", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 34, no. 6, 1990, pages 1026 - 1030, XP000921002
TIDWELL, R.R. ET AL: "Diarylamidine derivatives with one or both of the aryl moieties consisting of an indole or indole-like ring. Inhibitors of arginine-specific esteroproteases", JOURNAL OF MEDICINAL CHEMISTRY, vol. 21, no. 7, 1978, pages 613 - 623, XP000573913
FAIRLEY, T.A. ET AL: "Structure, DNA minor groove binding and base pair specificity of alkyl- and aryl- linked bis(amidinobenzimidazoles) and bis(amidinoindoles)", JOURNAL OF MEDICINAL CHEMISTRY, vol. 36, no. 12, 1993, pages 1746 - 1753, XP002067234
BELL, C.A. ET AL: "Structure-activity studies of dicationically substituted bis-benzimidazoles against Giardia lamblia: Correlation of antigiardial activity with DNA binding affinity and Giardial topoisomerase II inhibition", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, vol. 37, no. 12, 1993, pages 2668 - 2673, XP000972059
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