WO1998007708A1 - Isoxazoline derivatives useful as antimicrobials - Google Patents

Isoxazoline derivatives useful as antimicrobials Download PDF

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Publication number
WO1998007708A1
WO1998007708A1 PCT/US1997/013934 US9713934W WO9807708A1 WO 1998007708 A1 WO1998007708 A1 WO 1998007708A1 US 9713934 W US9713934 W US 9713934W WO 9807708 A1 WO9807708 A1 WO 9807708A1
Authority
WO
WIPO (PCT)
Prior art keywords
dihydro
optionally substituted
alkyl
phenyl
compound
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
Application number
PCT/US1997/013934
Other languages
English (en)
French (fr)
Inventor
Michael R. Barbachyn
Richard C. Thomas
Gary J. Cleek
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Pharmacia and Upjohn Co
Original Assignee
Pharmacia and Upjohn Co
Upjohn Co
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
Application filed by Pharmacia and Upjohn Co, Upjohn Co filed Critical Pharmacia and Upjohn Co
Priority to DE69716925T priority Critical patent/DE69716925T2/de
Priority to JP10510781A priority patent/JP2000516245A/ja
Priority to DK97937156T priority patent/DK0920421T3/da
Priority to AU39736/97A priority patent/AU3973697A/en
Priority to AT97937156T priority patent/ATE227277T1/de
Priority to SI9730449T priority patent/SI0920421T1/xx
Priority to EP97937156A priority patent/EP0920421B1/en
Publication of WO1998007708A1 publication Critical patent/WO1998007708A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • C07D413/10—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 carbon chain containing aromatic 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member

Definitions

  • This invention describes isoxazoline derivatives which are effective as antibacterial agents.
  • the compounds of the invention are novel and distinct from all other oxazolidinones in that the usual oxazolidinone rings are replaced by an isoxazoline moiety. These compounds have antibacterial activity comparable to the corresponding oxazolidinones. They are effective against a number of human and veterinary pathogens, including gram-positive aerobic bacteria such as multiply- resistant staphylococci and streptococci, as well as anaerobic organisms such as bacteroides and clostridia species, and acid-fast organisms such as Mycobacterium tuberculosis and Mycobacterium a ⁇ ium.
  • R 96 is a) an aromatic moiety having 6 to 10 carbon atoms, b) a 5-, or 6-membered aromatic optionally benzo-fused heterocyclic moiety having one to three atoms selected from the group consisting of S, N, and O, wherein the substituents (a) and (b) which can in turn be substituted with one or three -N0 2 , CF 3 , halo, -CN, OH, phenyl, C ⁇ g alkyl, C 1 _ 5 alkoxy, or C 1 5 acyl,
  • C 2 _ 5 alkynyl refers to at least one triple bond alkynyl group having two to five, two to eight, or two to ten carbon atoms respectively such as, for example, ethynyl, propynyl, butynyl, pentynyl, pentdiynyl, hexynyl, hexdiynyl, heptynyl, heptdiynyl, octynyl, octdiynyl, octatriynyl, nonynyl, nonediynyl, nonatriynyl and their isomeric forms thereof.
  • the reaction is diluted with ethyl acetate (100 mL) and water (50 mL).
  • the organic phase is separated and the aqueous phase is extracted with methylene chloride (4X50 mL).
  • the organic extracts are combined, dried over sodium sulfate, concentrated in vacuo and chromatographed on silica gel (230-400 mesh, 100 mL), eluting with chloroform/methanol (98/2).
  • the compound of Example 1, Step 1 can be prepared enantiomerically pure by a procedure from Ukaji, Y.; Sada, K.; Inomata, K. Chem. Lett. 1993, pp 1847-1580.
  • the reaction is diluted with ethyl acetate (100 mL) and water (50 mL).
  • the organic phase is separated, extracted with water (5 X 50 mL), dried over sodium sulfate, concentrated in vacuo and chromatographed on silica gel (230-400 mesh, 100 mL), eluting with methylene chloride/methanol (99/1).

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Communicable Diseases (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Oncology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
PCT/US1997/013934 1996-08-21 1997-08-15 Isoxazoline derivatives useful as antimicrobials Ceased WO1998007708A1 (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
DE69716925T DE69716925T2 (de) 1996-08-21 1997-08-15 Isoxazoline derivate und ihre verwendung als antimikroben
JP10510781A JP2000516245A (ja) 1996-08-21 1997-08-15 抗菌剤として有用なイソオキサゾリン誘導体類
DK97937156T DK0920421T3 (da) 1996-08-21 1997-08-15 Isoxazolinderivater anvendelige som antimikrobielle midler
AU39736/97A AU3973697A (en) 1996-08-21 1997-08-15 Isoxazoline derivatives useful as antimicrobials
AT97937156T ATE227277T1 (de) 1996-08-21 1997-08-15 Isoxazoline derivate und ihre verwendung als antimikroben
SI9730449T SI0920421T1 (en) 1996-08-21 1997-08-15 Isoxazoline derivatives useful as antimicrobials
EP97937156A EP0920421B1 (en) 1996-08-21 1997-08-15 Isoxazoline derivatives useful as antimicrobials

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US2428796P 1996-08-21 1996-08-21
US60/024,287 1996-08-21

Publications (1)

Publication Number Publication Date
WO1998007708A1 true WO1998007708A1 (en) 1998-02-26

Family

ID=21819822

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/013934 Ceased WO1998007708A1 (en) 1996-08-21 1997-08-15 Isoxazoline derivatives useful as antimicrobials

Country Status (10)

Country Link
US (2) US5990136A (enExample)
EP (1) EP0920421B1 (enExample)
JP (1) JP2000516245A (enExample)
AT (1) ATE227277T1 (enExample)
AU (1) AU3973697A (enExample)
DE (1) DE69716925T2 (enExample)
DK (1) DK0920421T3 (enExample)
ES (1) ES2186916T3 (enExample)
PT (1) PT920421E (enExample)
WO (1) WO1998007708A1 (enExample)

Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998054161A1 (en) * 1997-05-30 1998-12-03 Pharmacia & Upjohn Company Oxazolidinone antibacterial agents having a thiocarbonyl functionality
WO1999041244A1 (en) * 1998-02-13 1999-08-19 Pharmacia & Upjohn Company Substituted aminophenyl isoxazoline derivatives useful as antimicrobials
WO1999043671A1 (en) * 1998-02-25 1999-09-02 Pharmacia & Upjohn Company Substituted aminomethyl isoxazoline derivatives useful as antimicrobials
US6069145A (en) * 1996-01-27 2000-05-30 Zeneca Limited Piperazinonephenyloxazolidinone derivatives and their use as antibacterial agents
US6110936A (en) * 1996-05-11 2000-08-29 Zeneca Limited 3-phenyl-furan-(5H)-2-one and dihydrofuran-2-one derivatives as antibacterial agents
US6194441B1 (en) 1997-08-22 2001-02-27 Zeneca Ltd. Oxazolidinone derivatives and their use as antibacterial agents
WO2001040222A1 (en) * 1999-12-03 2001-06-07 Astrazeneca Ab Substituted isoxazolines and their use as antibacterial agents
US6255304B1 (en) 1997-05-30 2001-07-03 Pharmacia & Upjohn Company Oxazolidinone antibacterial agents having a thiocarbonyl functionality
WO2002053523A1 (en) * 2000-12-26 2002-07-11 Research Foundation Itsuu Laboratory Tropolone derivative
US6420349B1 (en) 1998-08-24 2002-07-16 Bristol-Myers Squibb Company Isoxazolinone antibacterial agents
US6465456B2 (en) 2000-06-29 2002-10-15 Bristol-Myers Squibb Company Isoxazolinone antibacterial agents
US6495551B1 (en) 1997-11-29 2002-12-17 Michael John Betts Substituted phenyloxazolidinones and their use as antibiotics
EP1107756A4 (en) * 1998-08-24 2003-02-26 Bristol Myers Squibb Co NEW ANTIBACTERIAL ISOXAZOLINONE
WO2003035073A1 (en) * 2001-10-25 2003-05-01 Astrazeneca Ab Isoxazoline derivatives useful as antimicrobials
US6605630B1 (en) 1997-08-22 2003-08-12 Syngenta Limited Antibiotic oxazolidinone derivatives
US6617339B1 (en) 1998-06-05 2003-09-09 Syngenta Limited Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them
US6689769B2 (en) 2000-12-21 2004-02-10 Pharmacia & Upjohn Company Antimicrobial quinolone derivatives and use of the same to treat bacterial infections
WO2005082900A3 (en) * 2004-01-28 2006-02-16 Pharmacia & Upjohn Co Llc Oxazolidinone amidoximes as antibacterial agents
US7141583B2 (en) 2000-04-25 2006-11-28 Astrazeneca Ab Oxazolidinone derivatives with antibiotic activity
AU2013327663B2 (en) * 2012-10-03 2016-03-10 Shell Internationale Research Maatschappij B.V. Optimizing performance of a drilling assembly
WO2021000684A1 (en) 2019-07-03 2021-01-07 Merck Sharp & Dohme Corp. Compounds and methods of use thereof as antibacterial agents

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AR038536A1 (es) * 2002-02-25 2005-01-19 Upjohn Co N-aril-2-oxazolidinona-5- carboxamidas y sus derivados
US7141588B2 (en) * 2002-02-25 2006-11-28 Pfizer, Inc. N-aryl-2-oxazolidinone-5-carboxamides and their derivatives
CA2515311A1 (en) * 2003-02-07 2004-08-19 Warner-Lambert Company Llc Antibacterial agents
WO2004069244A1 (en) * 2003-02-07 2004-08-19 Warner-Lambert Company Llc Oxazolidinone derivatives n-substituted by a bicyclic ring, for use as antibacterial agents
US7304050B2 (en) * 2003-09-16 2007-12-04 Pfizer Inc. Antibacterial agents
US20080262056A1 (en) * 2004-08-06 2008-10-23 Pfizer Inc Oxindole Oxazolidinones as Antibacterial Agents
AU2005285130B2 (en) * 2004-09-10 2011-09-15 Syngenta Limited Substituted isoxazoles as fungicides
ES2682303T3 (es) * 2010-08-05 2018-09-19 Zoetis Services Llc Derivados de isoxazolina como agentes antiparasitarios
US9173887B2 (en) 2010-12-22 2015-11-03 Abbvie Inc. Hepatitis C inhibitors and uses thereof

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3769295A (en) * 1967-08-26 1973-10-30 Ciba Geigy Corp Nitrofuryl derivatives of 5-substituted isoxazolines
US4283403A (en) * 1976-06-14 1981-08-11 Eli Lilly And Company Substituted isoxazolines for control of plant phytopathogens
EP0352781A2 (en) * 1988-07-29 1990-01-31 The Du Pont Merck Pharmaceutical Company Aminomethyloxooxazolidinyl arylbenzene derivatives useful as antibacterial agents
WO1994013649A1 (en) * 1992-12-08 1994-06-23 The Upjohn Company Tropone-substituted phenyloxazolidinone antibacterial agents
WO1995014680A1 (en) * 1993-11-26 1995-06-01 Pfizer Inc. 3-aryl-2-isoxazolines as antiinflammatory agents
EP0693491A1 (de) * 1994-07-20 1996-01-24 Bayer Ag 5-Gliedrige-heteroaryl-oxazolidinone als antibakterielle Arzneimittel
EP0694543A1 (de) * 1994-07-20 1996-01-31 Bayer Ag 6-gliedrige stickstoffhaltige Heteroaryl-Oxazolidinone

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5710159A (en) * 1996-05-09 1998-01-20 The Dupont Merck Pharmaceutical Company Integrin receptor antagonists

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3769295A (en) * 1967-08-26 1973-10-30 Ciba Geigy Corp Nitrofuryl derivatives of 5-substituted isoxazolines
US4283403A (en) * 1976-06-14 1981-08-11 Eli Lilly And Company Substituted isoxazolines for control of plant phytopathogens
EP0352781A2 (en) * 1988-07-29 1990-01-31 The Du Pont Merck Pharmaceutical Company Aminomethyloxooxazolidinyl arylbenzene derivatives useful as antibacterial agents
WO1994013649A1 (en) * 1992-12-08 1994-06-23 The Upjohn Company Tropone-substituted phenyloxazolidinone antibacterial agents
WO1995014680A1 (en) * 1993-11-26 1995-06-01 Pfizer Inc. 3-aryl-2-isoxazolines as antiinflammatory agents
EP0693491A1 (de) * 1994-07-20 1996-01-24 Bayer Ag 5-Gliedrige-heteroaryl-oxazolidinone als antibakterielle Arzneimittel
EP0694543A1 (de) * 1994-07-20 1996-01-31 Bayer Ag 6-gliedrige stickstoffhaltige Heteroaryl-Oxazolidinone

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
SAMI S. GHABRIAL ET AL: "Synthesis of biheteroaromatic compounds via the isoxazoline route", ACTA CHEMICA SCANDINAVICA. SERIES B - ORGANIC CHEMISTRY AND BIOCHEMISTRY., vol. 41, 1987, COPENHAGEN DK, pages 426 - 434, XP002045744 *

Cited By (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6069145A (en) * 1996-01-27 2000-05-30 Zeneca Limited Piperazinonephenyloxazolidinone derivatives and their use as antibacterial agents
US6350775B1 (en) 1996-05-11 2002-02-26 Zeneca Limited 3-phenyl-furan-(5H)-2-one and dihydrofuran-2-one derivatives as antibacterial agents
US6110936A (en) * 1996-05-11 2000-08-29 Zeneca Limited 3-phenyl-furan-(5H)-2-one and dihydrofuran-2-one derivatives as antibacterial agents
US6537986B2 (en) 1997-05-30 2003-03-25 Pharmacia & Upjohn Company Oxazolidinone antibacterial agents having a thiocarbonyl funtionality
US6255304B1 (en) 1997-05-30 2001-07-03 Pharmacia & Upjohn Company Oxazolidinone antibacterial agents having a thiocarbonyl functionality
WO1998054161A1 (en) * 1997-05-30 1998-12-03 Pharmacia & Upjohn Company Oxazolidinone antibacterial agents having a thiocarbonyl functionality
US6362189B1 (en) 1997-05-30 2002-03-26 Pharmacia And Upjohn Company Oxazolidinone antibacterial agents having a thiocarbonyl functionality
US6218413B1 (en) 1997-05-30 2001-04-17 Pharmacia & Upjohn Company Oxazolidinone antibacterial agents having a thiocarbonyl functionality
US6342513B1 (en) 1997-05-30 2002-01-29 Pharmacia And Upjohn Company Oxazolidinone antibacterial agents having a thiocarbonyl functionality
US6605630B1 (en) 1997-08-22 2003-08-12 Syngenta Limited Antibiotic oxazolidinone derivatives
US6194441B1 (en) 1997-08-22 2001-02-27 Zeneca Ltd. Oxazolidinone derivatives and their use as antibacterial agents
US6495551B1 (en) 1997-11-29 2002-12-17 Michael John Betts Substituted phenyloxazolidinones and their use as antibiotics
WO1999041244A1 (en) * 1998-02-13 1999-08-19 Pharmacia & Upjohn Company Substituted aminophenyl isoxazoline derivatives useful as antimicrobials
US6069141A (en) * 1998-02-13 2000-05-30 Pharmacia & Upjohn Company Substituted aminophenyl isoxazoline derivatives useful as antimicrobials
WO1999043671A1 (en) * 1998-02-25 1999-09-02 Pharmacia & Upjohn Company Substituted aminomethyl isoxazoline derivatives useful as antimicrobials
US6617339B1 (en) 1998-06-05 2003-09-09 Syngenta Limited Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them
US6420349B1 (en) 1998-08-24 2002-07-16 Bristol-Myers Squibb Company Isoxazolinone antibacterial agents
EP1107756A4 (en) * 1998-08-24 2003-02-26 Bristol Myers Squibb Co NEW ANTIBACTERIAL ISOXAZOLINONE
WO2001040222A1 (en) * 1999-12-03 2001-06-07 Astrazeneca Ab Substituted isoxazolines and their use as antibacterial agents
US7081538B1 (en) 1999-12-03 2006-07-25 Astrazeneca Ab Substituted isoxazolines and their use as antibacterial agents
US7141583B2 (en) 2000-04-25 2006-11-28 Astrazeneca Ab Oxazolidinone derivatives with antibiotic activity
US6465456B2 (en) 2000-06-29 2002-10-15 Bristol-Myers Squibb Company Isoxazolinone antibacterial agents
US6689769B2 (en) 2000-12-21 2004-02-10 Pharmacia & Upjohn Company Antimicrobial quinolone derivatives and use of the same to treat bacterial infections
US6869965B2 (en) 2000-12-21 2005-03-22 Pharmacia & Upjohn Company Antimicrobial quinolone derivatives and use of the same to treat bacterial infections
US7259187B2 (en) 2000-12-26 2007-08-21 Research Foundation Itsuu Laboratory Tropolone derivatives
AU2002222682B8 (en) * 2000-12-26 2008-05-29 Research Foundation Itsuu Laboratory Tropolone Derivatives
AU2002222682B2 (en) * 2000-12-26 2007-12-13 Research Foundation Itsuu Laboratory Tropolone Derivatives
WO2002053523A1 (en) * 2000-12-26 2002-07-11 Research Foundation Itsuu Laboratory Tropolone derivative
WO2003035073A1 (en) * 2001-10-25 2003-05-01 Astrazeneca Ab Isoxazoline derivatives useful as antimicrobials
US7022705B2 (en) 2001-10-25 2006-04-04 Astrazeneca Ab Isoxazoline derivatives useful as antimicrobials
WO2005082900A3 (en) * 2004-01-28 2006-02-16 Pharmacia & Upjohn Co Llc Oxazolidinone amidoximes as antibacterial agents
AU2013327663B2 (en) * 2012-10-03 2016-03-10 Shell Internationale Research Maatschappij B.V. Optimizing performance of a drilling assembly
WO2021000684A1 (en) 2019-07-03 2021-01-07 Merck Sharp & Dohme Corp. Compounds and methods of use thereof as antibacterial agents
WO2021000297A1 (en) * 2019-07-03 2021-01-07 Merck Sharp & Dohme Corp. Compounds and methods of use thereof as antibacterial agents
CN114341119A (zh) * 2019-07-03 2022-04-12 默沙东公司 化合物及其作为抗菌剂的使用方法
US12459933B2 (en) 2019-07-03 2025-11-04 Merck Sharp & Dohme Llc Compounds and methods of use thereof as antibacterial agents

Also Published As

Publication number Publication date
ATE227277T1 (de) 2002-11-15
US6093736A (en) 2000-07-25
PT920421E (pt) 2003-03-31
EP0920421A1 (en) 1999-06-09
DE69716925T2 (de) 2003-09-11
AU3973697A (en) 1998-03-06
DE69716925D1 (de) 2002-12-12
ES2186916T3 (es) 2003-05-16
DK0920421T3 (da) 2003-03-10
US5990136A (en) 1999-11-23
EP0920421B1 (en) 2002-11-06
JP2000516245A (ja) 2000-12-05

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