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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
ch2
ar
c10 alkyl
ch2ch2o
ch
Prior art date
Application number
PCT/US1997/015439
Other languages
French (fr)
Other versions
WO1998009970A2 (en
Inventor
Thomas Joseph Caggiano
Craig Eugene Caufield
Alexander Aleksey Grinfield
David Cheng Hu
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
Priority to US70959196A priority Critical
Priority to US08/709,591 priority
Application filed by American Home Prod filed Critical American Home Prod
Publication of WO1998009970A2 publication Critical patent/WO1998009970A2/en
Publication of WO1998009970A3 publication Critical patent/WO1998009970A3/en

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Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D498/00Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/12Heterocyclic 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
    • C07D498/18Bridged systems

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 (2)

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

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
AU41768/97A AU4176897A (en) 1996-09-09 1997-09-03 Alkylated rapamycin derivatives
JP51281598A JP2001500126A (en) 1996-09-09 1997-09-03 Alkylated rapamycin derivatives
EP19970939749 EP0927182A2 (en) 1996-09-09 1997-09-03 Alkylated rapamycin derivatives
CA 2266039 CA2266039A1 (en) 1996-09-09 1997-09-03 Alkylated rapamycin derivatives

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 (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6015815A (en) 1997-09-26 2000-01-18 Abbott Laboratories Tetrazole-containing rapamycin analogs with shortened half-lives
US7455853B2 (en) 1998-09-24 2008-11-25 Abbott Cardiovascular Systems Inc. Medical devices containing rapamycin analogs
TW557297B (en) * 1997-09-26 2003-10-11 Abbott Lab Rapamycin analogs having immunomodulatory activity, and pharmaceutical compositions containing same
US6890546B2 (en) 1998-09-24 2005-05-10 Abbott Laboratories Medical devices containing rapamycin analogs
CZ303611B6 (en) 2001-02-19 2013-01-09 Novartis Ag Pharmaceutical compositions containing rapamycin derivative and intended for treating solid tumors
WO2003018574A1 (en) * 2001-08-22 2003-03-06 Wyeth Rapamycin dialdehydes
ES2246409T3 (en) 2001-08-22 2006-02-16 Wyeth Rapamycin 29-enols.
PL216224B1 (en) 2002-02-01 2014-03-31 Ariad Pharmaceuticals, Inc. Phosphorus-containing compounds and 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 Preparation of O- alkylated rapamycin derivative
WO2006115509A2 (en) 2004-06-24 2006-11-02 Novartis Vaccines And Diagnostics Inc. Small molecule immunopotentiators and assays for their detection
KR20150003156A (en) * 2012-11-30 2015-01-08 항조우 질록스 파마 컴퍼니 리니티드 Rapamycin analogs and methods for making the same
CA2911104A1 (en) * 2013-06-20 2014-12-24 Novartis Ag Alkylation with an alkyl fluoroalkyl sulfonate

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
WO1994002136A1 (en) * 1992-07-17 1994-02-03 Smithkline Beecham Corporation Rapamycin derivatives
WO1994002485A1 (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
WO1994002136A1 (en) * 1992-07-17 1994-02-03 Smithkline Beecham Corporation Rapamycin derivatives
WO1994002485A1 (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
WO1998009970A2 (en) 1998-03-12
AU4176897A (en) 1998-03-26
JP2001500126A (en) 2001-01-09
EP0927182A2 (en) 1999-07-07
CA2266039A1 (en) 1998-03-12
CN1235608A (en) 1999-11-17

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