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WO2002009758A3 - Inhibitors of cellular efflux pumps of microbes - Google Patents

Inhibitors of cellular efflux pumps of microbes Download PDF

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Publication number
WO2002009758A3
WO2002009758A3 PCT/IN2001/000139 IN0100139W WO0209758A3 WO 2002009758 A3 WO2002009758 A3 WO 2002009758A3 IN 0100139 W IN0100139 W IN 0100139W WO 0209758 A3 WO0209758 A3 WO 0209758A3
Authority
WO
WIPO (PCT)
Prior art keywords
microbes
inhibitors
efflux pumps
compounds
cellular efflux
Prior art date
Application number
PCT/IN2001/000139
Other languages
French (fr)
Other versions
WO2002009758A2 (en
Inventor
Souza Noel J De
Mahesh V Patel
Shrikant V Gupte
Dilip J Upadhyay
Milind C Shukla
Nishith C Chaturvedi
Satish B Bhawsar
Sheela C Nair
Mohammed A Jafri
Habil F Khorakiwala
Original Assignee
Souza Noel J De
Mahesh V Patel
Shrikant V Gupte
Dilip J Upadhyay
Milind C Shukla
Nishith C Chaturvedi
Satish B Bhawsar
Sheela C Nair
Mohammed A Jafri
Habil F Khorakiwala
Wockhardt Ltd
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 US09/640,947 external-priority patent/US6750224B1/en
Priority claimed from US09/850,669 external-priority patent/US6608078B2/en
Priority claimed from PCT/IN2001/000100 external-priority patent/WO2001085728A2/en
Application filed by Souza Noel J De, Mahesh V Patel, Shrikant V Gupte, Dilip J Upadhyay, Milind C Shukla, Nishith C Chaturvedi, Satish B Bhawsar, Sheela C Nair, Mohammed A Jafri, Habil F Khorakiwala, Wockhardt Ltd filed Critical Souza Noel J De
Priority to AU2001280091A priority Critical patent/AU2001280091A1/en
Priority to EP01958373A priority patent/EP1305048A2/en
Priority to CA002417799A priority patent/CA2417799A1/en
Publication of WO2002009758A2 publication Critical patent/WO2002009758A2/en
Publication of WO2002009758A3 publication Critical patent/WO2002009758A3/en

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    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
    • 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
    • A61K31/65—Tetracyclines
    • 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
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7048—Compounds having saccharide radicals and heterocyclic rings having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin, digitoxin or digoxin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
    • 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
    • C07D401/02—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 two hetero rings
    • C07D401/04—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 two hetero rings directly linked by a ring-member-to-ring-member bond
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
    • C07D455/04—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/08—Bridged systems
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

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

Abstract

Compounds are described which are efflux pump inhibitors of cellular efflux pumps of microbes. Also described are methods of preparing such compounds, methods of using such efflux pump inhibitor compounds and pharmaceutical compositions which include such compounds.
PCT/IN2001/000139 2000-08-01 2001-07-31 Inhibitors of cellular efflux pumps of microbes WO2002009758A2 (en)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU2001280091A AU2001280091A1 (en) 2000-08-01 2001-07-31 Inhibitors of cellular efflux pumps of microbes
EP01958373A EP1305048A2 (en) 2000-08-01 2001-07-31 Inhibitors of cellular efflux pumps of microbes
CA002417799A CA2417799A1 (en) 2000-08-01 2001-07-31 Inhibitors of cellular efflux pumps of microbes

Applications Claiming Priority (12)

Application Number Priority Date Filing Date Title
US22220100P 2000-08-01 2000-08-01
US60/222,201 2000-08-01
US09/640,947 2000-08-17
US09/640,947 US6750224B1 (en) 1999-05-07 2000-08-17 Antibacterial optically pure benzoquinolizine carboxylic acids, processes, compositions and methods of treatment
IN0000111 2000-11-22
INPCT/IN00/00111 2000-11-22
US28629101P 2001-04-25 2001-04-25
US60/286,291 2001-04-25
US09/850,669 US6608078B2 (en) 2000-05-08 2001-05-07 Antibacterial chiral 8-(substituted piperidino)-benzo [i,j] quinolizines, processes, compositions and methods of treatment
US09/850,669 2001-05-07
INPCT/IN01/00100 2001-05-08
PCT/IN2001/000100 WO2001085728A2 (en) 2000-05-08 2001-05-08 Antibacterial chiral 8-(substituted piperidino)-benzo [i, j] quinolizines, processes, compositions and methods of treatment

Publications (2)

Publication Number Publication Date
WO2002009758A2 WO2002009758A2 (en) 2002-02-07
WO2002009758A3 true WO2002009758A3 (en) 2002-12-27

Family

ID=27517699

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2001/000139 WO2002009758A2 (en) 2000-08-01 2001-07-31 Inhibitors of cellular efflux pumps of microbes

Country Status (4)

Country Link
EP (1) EP1305048A2 (en)
AU (1) AU2001280091A1 (en)
CA (1) CA2417799A1 (en)
WO (1) WO2002009758A2 (en)

Families Citing this family (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6608078B2 (en) 2000-05-08 2003-08-19 Wockhardt Limited Antibacterial chiral 8-(substituted piperidino)-benzo [i,j] quinolizines, processes, compositions and methods of treatment
US7098219B2 (en) 2000-08-01 2006-08-29 Wockhart Limited Inhibitors of cellular efflux pumps of microbes
US6964966B2 (en) * 2001-04-25 2005-11-15 Wockhardt Limited Generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments
US6878713B2 (en) 2001-04-25 2005-04-12 Wockhardt Limited Generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments
AU2002361493A1 (en) * 2001-12-13 2003-06-23 Wockhardt Limited New generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments
EP1918289A3 (en) * 2002-05-28 2009-08-19 Wockhardt Limited Crystalline nadifloxacin arginine salt form
WO2003099815A1 (en) 2002-05-28 2003-12-04 Wockhardt Limited Crystalline fluoroquinolone arginine salt form
US7829543B2 (en) 2003-01-07 2010-11-09 Paratek Pharmaceuticals, Inc. Substituted polyamines as inhibitors of bacterial efflux pumps
GB2403653A (en) * 2003-07-10 2005-01-12 Secr Defence Use of fluoroquinone antibiotics for the treatment of plague
PL214849B1 (en) 2003-09-04 2013-09-30 Wockhardt Ltd Benzoquinolizine-2-carboxylic acid arginine salt tetrahydrate
WO2005026145A2 (en) * 2003-09-12 2005-03-24 Warner-Lambert Company Llc Quinolone antibacterial agents
WO2005070940A2 (en) * 2004-01-13 2005-08-04 Cumbre Pharmaceuticals Inc. Rifamycin derivatives effective against drug-resistant microbes
US7238694B2 (en) 2004-01-13 2007-07-03 Cumbre Pharmaceuticals, Inc. Rifamycin imino derivatives effective against drug-resistant microbes
US7947741B2 (en) 2004-03-17 2011-05-24 Mpex Pharmaceuticals, Inc. Use and administration of bacterial efflux pump inhibitors
US7994225B2 (en) 2004-03-17 2011-08-09 Rempex Pharmaceuticals, Inc. Bacterial efflux pump inhibitors for the treatment of ophthalmic and otic infections
DE102004035203A1 (en) 2004-07-21 2006-02-16 Bayer Healthcare Ag Substituted quinolones
DE102005030524A1 (en) 2005-06-30 2007-01-18 Aicuris Gmbh & Co. Kg Substituted quinolones II
DE102006005861A1 (en) 2006-02-09 2007-08-23 Aicuris Gmbh & Co. Kg Substituted quinolones III
US9155792B2 (en) 2006-02-13 2015-10-13 Trustees Of Boston University RecA inhibitors with antibiotic activity, compositions and methods of use
KR20130128483A (en) * 2006-03-07 2013-11-26 욱크하트 리미티드 Prodrugs of benzoquinolizine-2-carboxylic acid
CA2645376C (en) * 2006-03-13 2017-06-20 Activx Biosciences, Inc. Aminoquinolones as gsk-3 inhibitors
US20100234348A1 (en) * 2006-08-04 2010-09-16 Trustees Of Boston University Compositions and methods for potentiating antibiotic activity
US7902227B2 (en) 2007-07-27 2011-03-08 Janssen Pharmaceutica Nv. C-7 isoxazolinyl quinolone / naphthyridine derivatives useful as antibacterial agents
JP5426552B2 (en) 2007-09-11 2014-02-26 杏林製薬株式会社 Cyanoaminoquinolones and tetrazoloaminoquinolones as GSK-3 inhibitors
JP5373799B2 (en) 2007-09-12 2013-12-18 杏林製薬株式会社 Spirocyclic aminoquinolones as GSK-3 inhibitors
EP2406266B1 (en) 2009-03-11 2013-12-25 Kyorin Pharmaceutical Co., Ltd. 7-cycloalkylaminoquinolones as gsk-3 inhibitors
EP2536408A1 (en) * 2010-02-16 2012-12-26 Wockhardt Research Centre Efflux pump inhibitors
PT2751083T (en) 2011-08-31 2018-03-05 Otsuka Pharma Co Ltd Quinolone compound
CN103183684B (en) * 2011-12-29 2015-11-18 杭州师范大学 A kind of quinlone lactone compound and its preparation method and application
CN109486739B (en) * 2018-11-23 2022-02-01 上海海洋大学 Method for inducing vibrio parahaemolyticus to generate levofloxacin drug resistance

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Patent Citations (2)

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EP0300735A1 (en) * 1987-07-20 1989-01-25 CHINOIN Gyogyszer és Vegyészeti Termékek Gyára RT. Antimicrobial pharmaceutical composition
WO1997024128A1 (en) * 1995-12-27 1997-07-10 Bayer Corporation Otic microbial combinations

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Title
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E.M.MATEU-DE-ANTONIO, M.MARTIN: "In vitro efficacy of several antimicrobial combinations against Brucella canis and Brucella melitensis strains isolated from dogs", VETERINARY MICROBIOLOGY, vol. 45, no. 1, 1995, pages 1 - 10, XP001112917 *
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Also Published As

Publication number Publication date
CA2417799A1 (en) 2002-02-07
AU2001280091A1 (en) 2002-02-13
EP1305048A2 (en) 2003-05-02
WO2002009758A2 (en) 2002-02-07

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