AU705261B2 - Methods of combatting infectious diseases using dicationic bis-benzimidazoles - Google Patents
Methods of combatting infectious diseases using dicationic bis-benzimidazoles Download PDFInfo
- Publication number
- AU705261B2 AU705261B2 AU59566/96A AU5956696A AU705261B2 AU 705261 B2 AU705261 B2 AU 705261B2 AU 59566/96 A AU59566/96 A AU 59566/96A AU 5956696 A AU5956696 A AU 5956696A AU 705261 B2 AU705261 B2 AU 705261B2
- Authority
- AU
- Australia
- Prior art keywords
- bis
- structural formula
- benzimidazolyl
- pyrrole
- lower alkyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims abstract description 98
- 208000035473 Communicable disease Diseases 0.000 title description 4
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 241000222122 Candida albicans Species 0.000 claims abstract description 12
- 229940095731 candida albicans Drugs 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims description 87
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 58
- 150000003839 salts Chemical class 0.000 claims description 49
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 34
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 31
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- 229910052739 hydrogen Inorganic materials 0.000 claims description 22
- 201000007336 Cryptococcosis Diseases 0.000 claims description 18
- 206010028980 Neoplasm Diseases 0.000 claims description 17
- 241000221204 Cryptococcus neoformans Species 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 15
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 14
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 11
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- 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
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- 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)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/472996 | 1995-06-07 | ||
| US08/472,996 US5643935A (en) | 1995-06-07 | 1995-06-07 | Method of combatting infectious diseases using dicationic bis-benzimidazoles |
| PCT/US1996/008084 WO1996040145A1 (en) | 1995-06-07 | 1996-06-03 | Methods of combatting infectious diseases using dicationic bis-benzimidazoles |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AU5956696A AU5956696A (en) | 1996-12-30 |
| AU705261B2 true AU705261B2 (en) | 1999-05-20 |
Family
ID=23877744
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU59566/96A Ceased AU705261B2 (en) | 1995-06-07 | 1996-06-03 | Methods of combatting infectious diseases using dicationic bis-benzimidazoles |
Country Status (9)
| Country | Link |
|---|---|
| US (11) | US5643935A (enExample) |
| EP (1) | EP0831832B1 (enExample) |
| JP (1) | JPH11507036A (enExample) |
| AT (1) | ATE256464T1 (enExample) |
| AU (1) | AU705261B2 (enExample) |
| CA (1) | CA2223912A1 (enExample) |
| DE (1) | DE69631134T2 (enExample) |
| ES (1) | ES2213775T3 (enExample) |
| WO (1) | WO1996040145A1 (enExample) |
Families Citing this family (47)
| 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 |
| EP1685836A3 (en) * | 1998-09-17 | 2007-05-09 | University Of North Carolina At Chapel Hill | Antifungal activity of dicationic molecules |
| US6326395B1 (en) | 1998-09-17 | 2001-12-04 | Duke University | Antifungal activity of dicationic molecules |
| CN1297281C (zh) * | 1999-03-29 | 2007-01-31 | 希拉生物化学股份有限公司 | 治疗白血病的方法 |
| US7115665B1 (en) | 2000-11-16 | 2006-10-03 | Onocozyme Pharma, Inc. | Inhibitors of endo-exonuclease activity for treating cancer |
| ATE431734T1 (de) * | 1999-11-16 | 2009-06-15 | Oncozyme Pharma Inc | Pentamidine zur behandlung von krebs |
| 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 |
| 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 |
| 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 |
| 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. |
| US8404852B2 (en) | 2003-01-31 | 2013-03-26 | 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 |
| US7569591B2 (en) * | 2003-01-31 | 2009-08-04 | Vertex Pharmaceuticals Incorporated | Gyrase inhibitors and uses thereof |
| US7618974B2 (en) * | 2003-01-31 | 2009-11-17 | Vertex Pharmaceuticals Incorporated | Gyrase inhibitors and uses thereof |
| US7582641B2 (en) * | 2003-01-31 | 2009-09-01 | 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 |
| 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 |
| US7262223B2 (en) * | 2004-01-23 | 2007-08-28 | Neurochem (International) Limited | Amidine derivatives for treating amyloidosis |
| EP1734884B1 (en) | 2004-03-16 | 2021-06-16 | Guidance Endodontics, LLC | Endodontic files |
| 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 |
| US7817792B2 (en) * | 2006-05-04 | 2010-10-19 | Microsoft Corporation | Hyperlink-based softphone call and management |
| DE102007013854A1 (de) | 2007-03-20 | 2008-09-25 | Merck Patent Gmbh | Tetrahydrochinoline |
| DE102007013856A1 (de) | 2007-03-20 | 2008-09-25 | Merck Patent Gmbh | Substituierte Tetrahydropyrrolochinoline |
| 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 |
| ES2787599T3 (es) | 2009-05-13 | 2020-10-16 | Univ Virginia Patent Foundation | Inhibidores de leucemia inv(16) |
| US8481551B2 (en) | 2011-01-14 | 2013-07-09 | Vertex Pharmaceuticals Incorporated | Gyrase and topoisomerase IV inhibitors |
| CN103384666A (zh) | 2011-01-14 | 2013-11-06 | 沃泰克斯药物股份有限公司 | 固体形式的促旋酶抑制剂（r）-1-乙基-3-[5-[2-（1-羟基-1-甲基-乙基）嘧啶-5-基]-7-（四氢呋喃-2-基）-1氢-苯并咪唑-2-基]脲 |
| CN103403000B (zh) | 2011-01-14 | 2017-05-31 | 斯派罗吹耐姆公司 | 固体形式的促旋酶抑制剂（r）‑1‑乙基‑3‑[6‑氟‑5‑[2‑（1‑羟基‑1‑甲基‑乙基）嘧啶‑5‑基]‑7‑（四氢呋喃‑2‑基）‑1氢‑苯并咪唑‑2‑基]脲 |
| NZ612920A (en) | 2011-01-14 | 2015-10-30 | Vertex Pharma | Process of making gyrase and topoisomerase iv inhibitors |
| KR101941420B1 (ko) | 2011-06-20 | 2019-01-23 | 스페로 트리넴, 인코포레이티드 | 자이라제 및 토포이소머라제 억제제의 인산에스테르 |
| 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 |
| TWI595002B (zh) | 2012-07-18 | 2017-08-11 | 思沛羅三南公司 | （Ｒ）－２－（５－（２－（３－乙基脲基）－６－氟－７－（四氫呋喃－２－基）－１Ｈ－苯并［ｄ］咪唑－５－基）嘧啶－２－基）丙烷－２－基磷酸二氫鹽之固體形式及其鹽 |
| GB201506658D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| GB201506660D0 (en) | 2015-04-20 | 2015-06-03 | Cellcentric Ltd | Pharmaceutical compounds |
| WO2016186967A1 (en) * | 2015-05-15 | 2016-11-24 | Gilead Sciences, Inc. | Benzimidazole and imadazopyridine carboximidamide compounds having activity as inhibitors of indoleamine 2,3-dioxygenase |
| CN109475542A (zh) | 2016-07-27 | 2019-03-15 | 弗吉尼亚大学专利基金会 | 用于治疗癌症的组合疗法 |
| EP3493848B1 (en) * | 2016-08-02 | 2021-09-29 | Friedrich-Alexander-Universität Erlangen-Nürnberg | Heterocyclic diamidines |
Family Cites Families (12)
| 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 |
| 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 |
| US4963589A (en) * | 1988-10-25 | 1990-10-16 | The University Of North Carolina At Chapel Hill | Methods for treating Giardia lamblia |
| 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 CA CA002223912A patent/CA2223912A1/en not_active Abandoned
- 1996-06-03 AT AT96916817T patent/ATE256464T1/de not_active IP Right Cessation
- 1996-06-03 ES ES96916817T patent/ES2213775T3/es not_active Expired - Lifetime
- 1996-06-03 EP EP96916817A patent/EP0831832B1/en not_active Expired - Lifetime
- 1996-06-03 WO PCT/US1996/008084 patent/WO1996040145A1/en not_active Ceased
- 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 DE DE69631134T patent/DE69631134T2/de not_active Expired - Fee Related
-
1997
- 1997-05-29 US US08/865,424 patent/US5792782A/en not_active Expired - Lifetime
- 1997-05-29 US US08/865,427 patent/US5817686A/en not_active Expired - Fee Related
- 1997-05-29 US US08/865,425 patent/US5817687A/en not_active Expired - Fee Related
-
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 |
|---|---|
| ATE256464T1 (de) | 2004-01-15 |
| US5817686A (en) | 1998-10-06 |
| US6046226A (en) | 2000-04-04 |
| US5972969A (en) | 1999-10-26 |
| US6017941A (en) | 2000-01-25 |
| US5639755A (en) | 1997-06-17 |
| US6156779A (en) | 2000-12-05 |
| US5792782A (en) | 1998-08-11 |
| EP0831832A4 (en) | 1999-07-07 |
| US5817687A (en) | 1998-10-06 |
| DE69631134D1 (de) | 2004-01-29 |
| US5939440A (en) | 1999-08-17 |
| US6294565B1 (en) | 2001-09-25 |
| WO1996040145A1 (en) | 1996-12-19 |
| CA2223912A1 (en) | 1996-12-19 |
| EP0831832A1 (en) | 1998-04-01 |
| DE69631134T2 (de) | 2004-09-02 |
| AU5956696A (en) | 1996-12-30 |
| ES2213775T3 (es) | 2004-09-01 |
| JPH11507036A (ja) | 1999-06-22 |
| US5643935A (en) | 1997-07-01 |
| EP0831832B1 (en) | 2003-12-17 |
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