WO1998009970A3 - Alkylated rapamycin derivatives - Google Patents

Alkylated rapamycin derivatives Download PDF

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Publication number
WO1998009970A3
WO1998009970A3 PCT/US1997/015439 US9715439W WO9809970A3 WO 1998009970 A3 WO1998009970 A3 WO 1998009970A3 US 9715439 W US9715439 W US 9715439W WO 9809970 A3 WO9809970 A3 WO 9809970A3
Authority
WO
WIPO (PCT)
Prior art keywords
alkyl
ch2ch2o
independently
compounds
treatment
Prior art date
Application number
PCT/US1997/015439
Other languages
French (fr)
Other versions
WO1998009970A2 (en
Inventor
David Cheng Hu
Alexander Aleksey Grinfield
Thomas Joseph Caggiano
Craig Eugene Caufield
Original Assignee
American Home Prod
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 American Home Prod filed Critical American Home Prod
Priority to JP10512815A priority Critical patent/JP2001500126A/en
Priority to AU41768/97A priority patent/AU4176897A/en
Priority to EP97939749A priority patent/EP0927182A2/en
Priority to CA002266039A priority patent/CA2266039A1/en
Publication of WO1998009970A2 publication Critical patent/WO1998009970A2/en
Publication of WO1998009970A3 publication Critical patent/WO1998009970A3/en

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
    • C07D498/18—Bridged systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P37/00—Drugs for immunological or allergic disorders
    • A61P37/02—Immunomodulators
    • A61P37/06—Immunosuppressants, e.g. drugs for graft rejection

Landscapes

  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pulmonology (AREA)
  • Transplantation (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

This invention relates to compounds which possess immunosuppressive and/or anti tumor and/or antiinflammatory activity in vivo and/or inhibit thymocyte proliferation in vitro. These compounds are therefore useful in the treatment of transplantation rejection, autoimmune diseases such as lupus, rheumatoid arthritis, diabetes mellitus, multiple sclerosis and in the treatment of Candida albicans infections and also in treatment of diseases of inflammation. These compounds are represented by formula (I), wherein W and Y are OR1 and X and Z together form a bond or W and X are OR2 and Y and Z together form a bond, wherein: R1 is selected from -(CH¿2?)n-Ar where Ar is not phenyl, -(CH2CH2O)nCH3 where n is not 1, -CH2CH2CH2O(CH2CH2O)m-CH3, -(CH2)n-CH2CH(OR?3)CH¿2OR4 where R?3 and R4¿ are H, C¿1?-C10 alkyl, or R?3 and R4¿ together are ethylene, methylene or dimethylmethylene; -CH¿2?(CH2)n-OR?3¿ where R3 is not H, C¿1?-C10 alkyl, or C(O)C1-C10 alkyl; and -CH2(CH2)n-X where X is F, Cl, Br or I; R?2¿ is selected from H, C¿1?-C10 alkyl, Ar(CH2)n-, C3-C10 alkenyl, -(CH2CH2O)nCH3, -CH2CH2CH2O(CH2CH2O)m-CH3, -CH2(CH2)n-OR?3, -CH¿2(CH2)n-X where X is F, Cl, Br or I; and -(CH2)nCH2CH(OR5)CH2OR6 where R?5 and R6¿ are selected independently from H, C¿1?-C10 alkyl, -(CH2)n-Ar, -CONH(CH2)n-Ar or COC(CH3)2-(CH2)n-Ar, -COR?7¿ and -CO¿2R?7, where R7 is C1-C6 alkyl, C2-C6 alkenyl, or Ar; n = 1-10 independently; m = 1-5 independently; and Ar is selected independently from phenyl, pyridinyl, quinolinyl, indolyl, furanyl; 1,2,3-triazolyl and tetrazolyl, and a pharmaceutically acceptable acid addition salt where one can be formed.
PCT/US1997/015439 1996-09-09 1997-09-03 Alkylated rapamycin derivatives WO1998009970A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
JP10512815A JP2001500126A (en) 1996-09-09 1997-09-03 Alkylated rapamycin derivative
AU41768/97A AU4176897A (en) 1996-09-09 1997-09-03 Alkylated rapamycin derivatives
EP97939749A EP0927182A2 (en) 1996-09-09 1997-09-03 Alkylated rapamycin derivatives
CA002266039A CA2266039A1 (en) 1996-09-09 1997-09-03 Alkylated rapamycin derivatives

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US70959196A 1996-09-09 1996-09-09
US08/709,591 1996-09-09

Publications (2)

Publication Number Publication Date
WO1998009970A2 WO1998009970A2 (en) 1998-03-12
WO1998009970A3 true WO1998009970A3 (en) 1998-04-16

Family

ID=24850507

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US1997/015439 WO1998009970A2 (en) 1996-09-09 1997-09-03 Alkylated rapamycin derivatives

Country Status (6)

Country Link
EP (1) EP0927182A2 (en)
JP (1) JP2001500126A (en)
CN (1) CN1235608A (en)
AU (1) AU4176897A (en)
CA (1) CA2266039A1 (en)
WO (1) WO1998009970A2 (en)

Families Citing this family (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6890546B2 (en) 1998-09-24 2005-05-10 Abbott Laboratories Medical devices containing rapamycin analogs
US6015815A (en) * 1997-09-26 2000-01-18 Abbott Laboratories Tetrazole-containing rapamycin analogs with shortened half-lives
TW557297B (en) * 1997-09-26 2003-10-11 Abbott Lab Rapamycin analogs having immunomodulatory activity, and pharmaceutical compositions containing same
US7455853B2 (en) 1998-09-24 2008-11-25 Abbott Cardiovascular Systems Inc. Medical devices containing rapamycin analogs
LT3143995T (en) 2001-02-19 2019-01-25 Novartis Ag Rapamycin derivative for the treatment of lung cancer
CN1545512A (en) 2001-08-22 2004-11-10 惠氏公司 Rapamycin dialdehydes
ES2246409T3 (en) * 2001-08-22 2006-02-16 Wyeth 29-ENAPES OF RAPAMYCIN.
KR101004224B1 (en) 2002-02-01 2010-12-27 어리어드 파마슈티칼스, 인코포레이티드 Phosphorus-containing compounds & uses thereof
AU2003293529A1 (en) 2002-12-16 2004-07-29 Nitromed, Inc. Nitrosated and nitrosylated rapamycin compounds, compositions and methods of use
JP4716280B2 (en) * 2004-03-01 2011-07-06 テルモ株式会社 Process for producing O-alkylated rapamycin derivatives
EP1768662A2 (en) 2004-06-24 2007-04-04 Novartis Vaccines and Diagnostics, Inc. Small molecule immunopotentiators and assays for their detection
CA2863243A1 (en) * 2012-11-30 2014-06-05 Hangzhou Zylox Pharma Co., Ltd. Rafamycin analogs and methods for making same
US20160130280A1 (en) * 2013-06-20 2016-05-12 Novartis Ag Alkylation with an alkyl fluoroalkyl sulfonate
CA3103282A1 (en) 2018-06-15 2019-12-19 Navitor Pharmaceuticals, Inc. Rapamycin analogs and uses thereof
IL293549A (en) 2019-12-05 2022-08-01 Anakuria Therapeutics Inc Rapamycin analogs and uses thereof

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5151413A (en) * 1991-11-06 1992-09-29 American Home Products Corporation Rapamycin acetals as immunosuppressant and antifungal agents
US5258389A (en) * 1992-11-09 1993-11-02 Merck & Co., Inc. O-aryl, O-alkyl, O-alkenyl and O-alkynylrapamycin derivatives
WO1994002485A1 (en) * 1992-07-17 1994-02-03 Smithkline Beecham Corporation Rapamycin derivatives
WO1994002136A1 (en) * 1992-07-17 1994-02-03 Smithkline Beecham Corporation Rapamycin derivatives
WO1994009010A1 (en) * 1992-10-09 1994-04-28 Sandoz Ltd. O-alkylated rapamycin derivatives and their use, particularly as immunosuppressants
WO1994024304A1 (en) * 1993-04-08 1994-10-27 Sandoz Ltd. Rapamycin assay

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5151413A (en) * 1991-11-06 1992-09-29 American Home Products Corporation Rapamycin acetals as immunosuppressant and antifungal agents
WO1994002485A1 (en) * 1992-07-17 1994-02-03 Smithkline Beecham Corporation Rapamycin derivatives
WO1994002136A1 (en) * 1992-07-17 1994-02-03 Smithkline Beecham Corporation Rapamycin derivatives
WO1994009010A1 (en) * 1992-10-09 1994-04-28 Sandoz Ltd. O-alkylated rapamycin derivatives and their use, particularly as immunosuppressants
US5258389A (en) * 1992-11-09 1993-11-02 Merck & Co., Inc. O-aryl, O-alkyl, O-alkenyl and O-alkynylrapamycin derivatives
WO1994024304A1 (en) * 1993-04-08 1994-10-27 Sandoz Ltd. Rapamycin assay

Also Published As

Publication number Publication date
CN1235608A (en) 1999-11-17
CA2266039A1 (en) 1998-03-12
EP0927182A2 (en) 1999-07-07
AU4176897A (en) 1998-03-26
WO1998009970A2 (en) 1998-03-12
JP2001500126A (en) 2001-01-09

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