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WO1996036612A1 - Utilisation de trisbenzimidazols en tant qu'inhibiteurs de la topoisomerase i - Google Patents

Utilisation de trisbenzimidazols en tant qu'inhibiteurs de la topoisomerase i Download PDF

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Publication number
WO1996036612A1
WO1996036612A1 PCT/US1996/006853 US9606853W WO9636612A1 WO 1996036612 A1 WO1996036612 A1 WO 1996036612A1 US 9606853 W US9606853 W US 9606853W WO 9636612 A1 WO9636612 A1 WO 9636612A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
alkyl
mmol
topoisomerase
pyridyl
Prior art date
Application number
PCT/US1996/006853
Other languages
English (en)
Inventor
Edmond J. Lavoie
Leroy Fong Liu
Qun Sun
Original Assignee
Rutgers, The State University Of New Jersey
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.)
Filing date
Publication date
Priority claimed from US08/442,657 external-priority patent/US5807874A/en
Priority claimed from US08/618,988 external-priority patent/US5767142A/en
Application filed by Rutgers, The State University Of New Jersey filed Critical Rutgers, The State University Of New Jersey
Priority to HU9900071A priority Critical patent/HUP9900071A3/hu
Priority to AU57466/96A priority patent/AU713317B2/en
Priority to EP96915784A priority patent/EP0839140A1/fr
Priority to JP8534375A priority patent/JPH11508229A/ja
Priority to BR9608476A priority patent/BR9608476A/pt
Priority to NZ307959A priority patent/NZ307959A/en
Priority to PL96324034A priority patent/PL324034A1/xx
Publication of WO1996036612A1 publication Critical patent/WO1996036612A1/fr

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/18—Benzimidazoles; Hydrogenated benzimidazoles with aryl radicals directly attached in position 2

Definitions

  • Y' is preferably H or CH 3 .
  • the present phosphoramidate compounds may be orally administered, for example, in combination with a pharmaceutically acceptable vehicle such as an inert diluent or an assimilable edible carrier. They may be enclosed in hard or soft shell gelatin capsules, may be compressed into tablets, or may be incorporated directly with the food of the patient's diet.
  • a pharmaceutically acceptable vehicle such as an inert diluent or an assimilable edible carrier.
  • the active compound may be combined with one or more excipients and used in the form of ingestible tablets, buccal tablets, troches, capsules, elixirs, suspensions, syrups, wafers, and the like.
  • Such compositions and preparations should contain at least 0.1% of active compound.
  • isotonic agents for example, sugars, buffers or sodium chloride.
  • Prolonged absorption of the injectable compositions can be brought about by the use in the compositions of agents delaying absorption, for example, aluminum monostearate and gelatin.

Landscapes

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

Abstract

Cette invention concerne des inhibiteurs anti-néoplasiques de la topoisomérase I, de la formule (I), ou un sel de ceux-ci acceptable du point de vue pharmaceutique. Dans cette formule, Ar représente un aryle en C6-C12 ou un hétéroaryle (comportant de 5 à 12 éléments) comprenant 1-3 N, S ou O non peroxydé, N n'étant pas substitué ou substitué par alkyle en C1-C4, X représente H, CN, CHO, OH, acétyle, CF3, O(C1-C4)alkyle, NO2, NH2, halogène ou haloalkyle (C1-C4); chaque Y est individuellement H, alkyle (C1-C4) ou aralkyle, Y' représente H ou alkyle (C1-C4), n vaut 0 ou 1 et chaque Z est individuellement H, alkyle (C1-C4), halogène ou haloalkyle (C1-C4).
PCT/US1996/006853 1995-05-17 1996-05-14 Utilisation de trisbenzimidazols en tant qu'inhibiteurs de la topoisomerase i WO1996036612A1 (fr)

Priority Applications (7)

Application Number Priority Date Filing Date Title
HU9900071A HUP9900071A3 (en) 1995-05-17 1996-05-14 Tribenzimidazoles useful as topoisomerase i inhibitors, pharmaceutical compositions containing them and their use
AU57466/96A AU713317B2 (en) 1995-05-17 1996-05-14 Trisbenzimidazoles useful as topoisomerase I inhibitors
EP96915784A EP0839140A1 (fr) 1995-05-17 1996-05-14 Utilisation de trisbenzimidazols en tant qu'inhibiteurs de la topoisomerase i
JP8534375A JPH11508229A (ja) 1995-05-17 1996-05-14 トポイソメラーゼインヒビターとして有用なトリスベンズイミダゾール類
BR9608476A BR9608476A (pt) 1995-05-17 1996-05-14 Composto processo para inibir o crescimento de uma célula tumoral de mam¡fero e composicão terapéutica
NZ307959A NZ307959A (en) 1995-05-17 1996-05-14 Substituted tribenzimidazole derivatives where the substituent can be aryl or heteroaryl and medicaments
PL96324034A PL324034A1 (en) 1995-05-17 1996-05-14 Tribenzimidazoles useful as inhibitors of topoisomerase i

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US08/442,657 US5807874A (en) 1995-05-17 1995-05-17 Trisbenzimidazoles useful as topoisomerase I inhibitors
US08/618,988 1996-03-20
US08/618,988 US5767142A (en) 1996-03-20 1996-03-20 Trisbenzimidazoles useful as topoisomerase I inhibitors
US08/442,657 1996-03-20

Publications (1)

Publication Number Publication Date
WO1996036612A1 true WO1996036612A1 (fr) 1996-11-21

Family

ID=27033238

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1996/006853 WO1996036612A1 (fr) 1995-05-17 1996-05-14 Utilisation de trisbenzimidazols en tant qu'inhibiteurs de la topoisomerase i

Country Status (10)

Country Link
EP (1) EP0839140A1 (fr)
JP (1) JPH11508229A (fr)
AU (1) AU713317B2 (fr)
BR (1) BR9608476A (fr)
CA (1) CA2221248A1 (fr)
CZ (1) CZ363197A3 (fr)
HU (1) HUP9900071A3 (fr)
NZ (1) NZ307959A (fr)
PL (1) PL324034A1 (fr)
WO (1) WO1996036612A1 (fr)

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998031673A1 (fr) * 1997-01-21 1998-07-23 Rutgers, The State University Of New Jersey Terbenzimidazoles s'utilisant dans un traitement medical (inhibiteurs de topoisomerase)
WO1999033824A1 (fr) * 1997-12-31 1999-07-08 Rutgers, The State University Of New Jersey Poisons topo-isomerase heterocycliques
WO1999041241A1 (fr) * 1998-02-12 1999-08-19 Rutgers, The State University Of New Jersey Poisons topoisomerase heterocycliques
US6740650B2 (en) 1999-10-29 2004-05-25 Rutgers, The State University Of New Jersey Heterocyclic cytotoxic agents
US6833373B1 (en) 1998-12-23 2004-12-21 G.D. Searle & Co. Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia
US6858598B1 (en) 1998-12-23 2005-02-22 G. D. Searle & Co. Method of using a matrix metalloproteinase inhibitor and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia
US6964964B2 (en) 2001-11-14 2005-11-15 Rutgers The State University Of New Jersey Topoisomerase poison agents
US6987109B2 (en) 2001-11-14 2006-01-17 Rutgers, The State University Of New Jersey Solubilized topoisomerase poison agents
US6989387B2 (en) 2002-08-09 2006-01-24 Rutgers, The State University Of New Jersey Nitro and amino substituted topoisomerase agents
US6992089B2 (en) 2002-08-09 2006-01-31 Rutgers, The University Of New Jersey Nitro and amino substituted topoisomerase agents
US6992088B2 (en) 2002-08-09 2006-01-31 Rutgers, The State University Of New Jersey Nitro and amino substituted heterocycles as topoisomerase I targeting agents
US7049315B2 (en) 2001-11-14 2006-05-23 Rutgers, The State University Of New Jersey Solubilized topoisomerase poisons
US7208492B2 (en) 2002-11-12 2007-04-24 Rutgers, The State University Of New Jersey Topoisomerase-targeting agents
US7319105B2 (en) 2001-11-14 2008-01-15 Rutgers, The State University Of New Jersey Cytotoxic agents
US9321781B2 (en) 2009-05-01 2016-04-26 Rutgers, The State University Of New Jersey Topoisomerase inhibitors
US9562051B2 (en) 2009-03-06 2017-02-07 Rutgers, The State University Of New Jersey Methylenedioxybenzo [I] phenanthridine derivatives used to treat cancer
US11091498B2 (en) 2016-04-04 2021-08-17 Rutgers, The State University Of New Jersey Topoisomerase poisons

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
A.Y. CHEN ET AL.: "A New Mammalian DNA Topoisomerase I Poison Hoechst 33342: Cytotoxicity and Drug Resistance in Human Cell Cultures", CANCER RESEARCH, vol. 53, no. 6, 15 March 1993 (1993-03-15), MD US, pages 1332 - 1337, XP002010634 *
Q. SUN ET AL.: "Synthesis and Evaluation of Terbenzimidazoles as Topoisomerase I Inhibitors", JOURNAL OF MEDICINAL CHEMISTRY, vol. 38, no. 18, 1 September 1995 (1995-09-01), WASHINGTON US, pages 3638 - 3644, XP002010635 *

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998031673A1 (fr) * 1997-01-21 1998-07-23 Rutgers, The State University Of New Jersey Terbenzimidazoles s'utilisant dans un traitement medical (inhibiteurs de topoisomerase)
US6995154B2 (en) 1997-12-31 2006-02-07 Rutgers, The State University Of New Jersey Heterocyclic topoisomerase poisons
WO1999033824A1 (fr) * 1997-12-31 1999-07-08 Rutgers, The State University Of New Jersey Poisons topo-isomerase heterocycliques
AU753268B2 (en) * 1997-12-31 2002-10-10 Jun Sung Kim Heterocyclic topoisomerase poisons
US6667302B2 (en) 1997-12-31 2003-12-23 Rutgers, The State University Of New Jersey Heterocyclic topoisomerase poisons
WO1999041241A1 (fr) * 1998-02-12 1999-08-19 Rutgers, The State University Of New Jersey Poisons topoisomerase heterocycliques
US6063801A (en) * 1998-02-12 2000-05-16 Rutgers, The State University Of New Jersey Heterocyclic topoisomerase poisons
US6221892B1 (en) 1998-02-12 2001-04-24 The State Of University Of New Jersey, Rutgers Heterocyclic topoisomerase poisons
US6399642B2 (en) 1998-02-12 2002-06-04 Rutgers, The State University Of New Jersey Benzimidazole topoisomerase poisons
US6833373B1 (en) 1998-12-23 2004-12-21 G.D. Searle & Co. Method of using an integrin antagonist and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia
US6858598B1 (en) 1998-12-23 2005-02-22 G. D. Searle & Co. Method of using a matrix metalloproteinase inhibitor and one or more antineoplastic agents as a combination therapy in the treatment of neoplasia
US6740650B2 (en) 1999-10-29 2004-05-25 Rutgers, The State University Of New Jersey Heterocyclic cytotoxic agents
US7517883B2 (en) 2001-11-14 2009-04-14 Rutgers, The State University Of New Jersey Solubilized topoisomerase poisons
US6964964B2 (en) 2001-11-14 2005-11-15 Rutgers The State University Of New Jersey Topoisomerase poison agents
US8389721B2 (en) 2001-11-14 2013-03-05 Rutgers, The State University Of New Jersey Solubilized topoisomerase poisons
US7781587B2 (en) 2001-11-14 2010-08-24 Rutgers, The State University Of New Jersey Solubilized topoisomerase poisons
US6987109B2 (en) 2001-11-14 2006-01-17 Rutgers, The State University Of New Jersey Solubilized topoisomerase poison agents
US7049315B2 (en) 2001-11-14 2006-05-23 Rutgers, The State University Of New Jersey Solubilized topoisomerase poisons
US7468366B2 (en) 2001-11-14 2008-12-23 Rutgers, The State University Of New Jersey Cytotoxic agents
US7319105B2 (en) 2001-11-14 2008-01-15 Rutgers, The State University Of New Jersey Cytotoxic agents
US6989387B2 (en) 2002-08-09 2006-01-24 Rutgers, The State University Of New Jersey Nitro and amino substituted topoisomerase agents
US6992088B2 (en) 2002-08-09 2006-01-31 Rutgers, The State University Of New Jersey Nitro and amino substituted heterocycles as topoisomerase I targeting agents
US6992089B2 (en) 2002-08-09 2006-01-31 Rutgers, The University Of New Jersey Nitro and amino substituted topoisomerase agents
US7208492B2 (en) 2002-11-12 2007-04-24 Rutgers, The State University Of New Jersey Topoisomerase-targeting agents
US7858627B2 (en) 2002-11-12 2010-12-28 Rutgers, The State University Of New Jersey Topoisomerase-targeting agents
US9562051B2 (en) 2009-03-06 2017-02-07 Rutgers, The State University Of New Jersey Methylenedioxybenzo [I] phenanthridine derivatives used to treat cancer
US10179789B2 (en) 2009-03-06 2019-01-15 Rutgers, The State University Of New Jersey Methylenedioxybenzo [I] phenanthridine derivatives used to treat cancer
US9321781B2 (en) 2009-05-01 2016-04-26 Rutgers, The State University Of New Jersey Topoisomerase inhibitors
US11091498B2 (en) 2016-04-04 2021-08-17 Rutgers, The State University Of New Jersey Topoisomerase poisons

Also Published As

Publication number Publication date
BR9608476A (pt) 1999-08-17
HUP9900071A2 (hu) 2000-03-28
CA2221248A1 (fr) 1996-11-21
EP0839140A1 (fr) 1998-05-06
HUP9900071A3 (en) 2002-01-28
CZ363197A3 (cs) 1998-05-13
AU5746696A (en) 1996-11-29
MX9708822A (es) 1998-06-30
AU713317B2 (en) 1999-11-25
NZ307959A (en) 1998-08-26
PL324034A1 (en) 1998-05-11
JPH11508229A (ja) 1999-07-21

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