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1.
公开(公告)号:US20100173913A1
公开(公告)日:2010-07-08
申请号:US12724203
申请日:2010-03-15
申请人: Eddy Jean Edgard Freyne , Marc Willems , Pierre Henri Storck , Virginie Sophie Poncelet , Kristof Van Emelen , Peter Jacobus Johannes Antonius Buijnsters , Werner Constant Johan Embrechts , Timothy Pietro Suren Perera
发明人: Eddy Jean Edgard Freyne , Marc Willems , Pierre Henri Storck , Virginie Sophie Poncelet , Kristof Van Emelen , Peter Jacobus Johannes Antonius Buijnsters , Werner Constant Johan Embrechts , Timothy Pietro Suren Perera
IPC分类号: A61K31/529 , C07D498/18 , A61P35/00 , C07D487/18
CPC分类号: C07D498/16 , C07D471/04 , C07D487/04 , C07D487/16 , C07D487/22
摘要: The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein a1-a2=a3-a4 represents a divalent radical selected from N—CH═CH—CH, N—CH═N—CH or CH—CH═N—CH; Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR13—C1-5alkyl-, —C1-6alkyl-NH—CO— or —CO—NH—C1-6alkyl-; X1 represents —O— or —NR11—; X2 represents —C1-2alkyl-, —O—C1-2alkyl, —O— or —O—CH2—; R1 represents hydrogen or halo; R2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C1-4alkyloxycarbonyl-, Het16-carbonyl- or Ar5; R3 represents hydrogen; R4 represents hydroxy, C1-4alkyloxy-, Ar4—C1-4alkyloxy or R4 represents C1-4alkyloxy substituted with one or where possible two or more substituents selected from C1-4alkyloxy- or Het2-; R11 represents hydrogen; R12 represents hydrogen, C1-4alkyl- or C1-4alkyl-oxy-carbonyl-; R13 represents Het14-C1-4alkyl, in particular morpholinyl-C1-4alkyl; Het2 represents a heterocycle selected from morpholinyl or piperidinyl optionally substituted with C1-4alkyl-, preferably methyl; Het14 represents morpholinyl; Het16 represents a heterocycle selected from morpholinyl or pyrrolidinyl; Ar4 represents phenyl; Ar5 represents phenyl optionally substituted with cyano.
摘要翻译: 本发明涉及N-氧化物形式的化合物,其药学上可接受的加成盐和立体化学异构体,其中a1-a2 = a3-a4表示选自N-CH = CH-CH,N- CH = N-CH或CH-CH = N-CH; Z表示NH; Y表示-C3-9烷基 - ,-C1-5烷基-NR13-C1-5烷基 - ,C1-6烷基-NH-CO-或-CO-NH-C1-6烷基 - ; X1表示-O-或-NR11-; X2表示-C1-2烷基 - , - O-C1-2烷基,-O-或-O-CH2-; R1表示氢或卤素; R 2表示氢,氰基,卤素,羟基羰基 - ,C 1-4烷氧基羰基 - ,Het 16 - 羰基 - 或Ar 5; R3表示氢; R 4表示羟基,C 1-4烷氧基 - ,Ar 4 -C 1-4烷氧基或R 4表示被一个或多个可能的两个或多个选自C 1-4烷氧基或Het 2-的取代基取代的C 1-4烷氧基; R11表示氢; R 12表示氢,C 1-4烷基 - 或C 1-4烷基 - 氧基 - 羰基 - ; R13表示Het14-C1-4烷基,特别是吗啉基-C 1-4烷基; Het2表示选自任选被C 1-4烷基,优选甲基取代的吗啉基或哌啶基的杂环; Het14代表吗啉基; Het16表示选自吗啉基或吡咯烷基的杂环; Ar4表示苯基; Ar 5表示任选被氰基取代的苯基。
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公开(公告)号:US20080139601A1
公开(公告)日:2008-06-12
申请号:US10596509
申请日:2004-12-15
申请人: Eddy Jean Edgard Freyne , Peter Jacobus Johannes Antonius Buijnsters , Kristof Van Emelen , Werner Constant Johan Embrechts , Timothy Pietro Suren Perera
发明人: Eddy Jean Edgard Freyne , Peter Jacobus Johannes Antonius Buijnsters , Kristof Van Emelen , Werner Constant Johan Embrechts , Timothy Pietro Suren Perera
IPC分类号: A61K31/4745 , C07D487/02 , A61P35/00
CPC分类号: C07D215/54 , A61K31/4748 , C07D498/06
摘要: The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR12—C1-5alkyl-, —C1-6alkyl-NH—CO— or —CO—NH—C1-6alkyl-; X1 represents —O—; X2 represents a direct bond, —NR11—C1-2alkyl-, —NR11—CH2—, —C1-2alkyl-, —O—C1-2alkyl, —O— or —O—CH2—; R1 represents hydrogen or halo; R2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C1-4alkyloxycarbonyl-, Het16-carbonyl- or Ar5; R3 represents hydrogen, hydroxy, C1-4alkyloxy-, Ar4—C1-4alkyloxy or R3 represents C1-4alkyloxy substituted with one or where possible two or more substituents selected from C1-4alkyloxy- or Het2-; R10 represents hydrogen; R11 represents hydrogen, C1-4alkyl- or C1-4alkyl-oxy-carbonyl-; R12 represents Het14-C1-4alkyl, in particular morpholinyl-C1-4alkyl; Het2 represents a heterocycle selected from morpholinyl or piperidinyl optionally substituted with C1-4alkyl-, preferably methyl; Het14 represents morpholinyl; Het16 represents a heterocycle selected from morpholinyl or pyrrolidinyl; Ar4 represents phenyl; Ar5 represents phenyl optionally substituted with cyano.
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公开(公告)号:US20100069424A1
公开(公告)日:2010-03-18
申请号:US12624708
申请日:2009-11-24
申请人: Eddy Jean Edgard FREYNE , Peter Jacobus Johannes Antonius Buijnsters , Kristof Van Emelen , Werner Constant Johan Embrechts , Timothy Pietro Suren Perera
发明人: Eddy Jean Edgard FREYNE , Peter Jacobus Johannes Antonius Buijnsters , Kristof Van Emelen , Werner Constant Johan Embrechts , Timothy Pietro Suren Perera
IPC分类号: C07D498/08 , A61K31/439
CPC分类号: C07D215/54 , A61K31/4748 , C07D498/06
摘要: The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR12—C1-5alkyl-, —C1-6alkyl-NH—CO— or —CO—NH—C1-6alkyl-; X1 represents —O—; X2 represents a direct bond, —NR11—C1-2alkyl-, —NR11—CH2—, —C1-2alkyl-, —O—C1-2alkyl, —O— or —O—CH2—; R1 represents hydrogen or halo; R2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C1-4alkyloxycarbonyl-, Het16-carbonyl- or Ar5; R3 represents hydrogen, hydroxy, C1-4alkyloxy-, Ar4—C1-4alkyloxy or R3 represents C1-4alkyloxy substituted with one or where possible two or more substituents selected from C1-4alkyloxy- or Het2-; R10 represents hydrogen; R11 represents hydrogen, C1-4alkyl- or C1-4alkyl-oxy-carbonyl-; R12 represents Het14-C1-4alkyl, in particular morpholinyl-C1-4alkyl; Het2 represents a heterocycle selected from morpholinyl or piperidinyl optionally substituted with C1-4alkyl-, preferably methyl; Het14 represents morpholinyl; Het16 represents a heterocycle selected from morpholinyl or pyrrolidinyl; Ar4 represents phenyl; Ar5 represents phenyl optionally substituted with cyano.
摘要翻译: 本发明涉及下式的化合物:N-氧化物形式,其药学上可接受的加成盐和立体化学异构形式,其中Z代表NH; Y表示-C3-9烷基,-C1-5烷基-NR12-C1-5烷基,-C 1-6烷基-NH-CO-或-CO-NH-C 1-6烷基; X1表示-O-; X 2表示直接键,-NR 11 -C 1-2烷基 - , - NR 11 -CH 2 - , - C 1-2烷基 - , - O-C 1-2烷基,-O-或-O-CH 2 - 。 R1表示氢或卤素; R 2表示氢,氰基,卤素,羟基羰基 - ,C 1-4烷氧基羰基 - ,Het 16 - 羰基 - 或Ar 5; R 3表示氢,羟基,C 1-4烷氧基 - ,Ar 4 -C 1-4烷氧基或R 3表示被一个或多个可能的两个或多个选自C 1-4烷氧基 - 或Het 2 - 的取代基取代的C 1-4烷氧基; R10表示氢; R11表示氢,C1-4烷基或C1-4烷基 - 氧 - 羰基 - ; R12表示Het14-C1-4烷基,特别是吗啉基-C 1-4烷基; Het2表示选自任选被C 1-4烷基,优选甲基取代的吗啉基或哌啶基的杂环; Het14代表吗啉基; Het16表示选自吗啉基或吡咯烷基的杂环; Ar4表示苯基; Ar 5表示任选被氰基取代的苯基。
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公开(公告)号:US20100105668A1
公开(公告)日:2010-04-29
申请号:US12624637
申请日:2009-11-24
申请人: Eddy Jean Edgard Freyne , Timothy Pietro Suren Perera , Peter Jacobus Johannes Antonius Buijnsters , Marc Willems , Gaston Stanislas Marcella Diels , Werner Constant Johan Embrechts , Peter ten Holte , Frederik Jan Rita Rombouts , Carsten Schultz-Fademrecht
发明人: Eddy Jean Edgard Freyne , Timothy Pietro Suren Perera , Peter Jacobus Johannes Antonius Buijnsters , Marc Willems , Gaston Stanislas Marcella Diels , Werner Constant Johan Embrechts , Peter ten Holte , Frederik Jan Rita Rombouts , Carsten Schultz-Fademrecht
IPC分类号: A61K31/541 , C07D239/70 , A61K31/517 , C07D413/02 , A61K31/5377 , C07D417/02 , C07C211/00 , C07D239/72
CPC分类号: C07D498/06 , C07C229/16 , C07C229/40 , C07D239/88 , C07D239/93 , C07D239/94
摘要: The present invention concerns the compounds of formula wherein Z represents NH; Y represents —C3-9alkyl-, —C2-9alkenyl-, —C3-7alkyl-CO—NH optionally substituted with amino, mono- or di(C1-4alkyl)amino or C1-4alkyloxycarbonylamino-, —C3-7alkenyl-CO—NH— optionally substituted with amino, mono- or di(C1-4alkyl)amino- or C1-4alkyloxycarbonylamino-, C1-5alkyl-NR13—C1-5alkyl-, —C1-5alkyl-NR14—CO—C1-5alkyl-, —C1-6alkyl-CO—NH—, —C1-5alkyl-CO NR15—C1-5alkyl-, —C1-3alkyl-NH—CO-Het20-, —C1-2alkyl-CO-Het21-CO—, —C1-2alkyl-NH—CO—CR16R17—NH—, —C1-2alkyl-CO—NH—CR18R19—CO—, —C1-2alkyl-CO—NR20—C1-3alkyl-CO—, or —NR22—CO—C1-3alkyl-NH—; X1 represents a direct bond, O or —O—C1-2alkyl-; X2 represents a direct bond, —CO—C1-2alkyl-, NR12, —NR12—C1-2alkyl-, —O—N═CH— or —C1-2alkyl-; R1 and R2 are hydrogen or halo; R3 are hydrogen; R4 represents hydrogen or C1-4alkyloxy; R12 and R13 are hydrogen or C1-4alkyl; R14 and R15 are hydrogen; R16 and R17 each independently represent hydrogen or C1-4alkyl; R18 and R19 are hydrogen or C1-4alkyl optionally substituted with phenyl or hydroxy; R20 and R21 are hydrogen or C1-4alkyl optionally substituted with C1-4alkyloxy; Het20, Het21 and Het22 are a heterocycle selected from the group consisting pyrrolidinyl, 2-pyrrolidinonyl or piperidinyl optionally substituted with hydroxy.
摘要翻译: 本发明涉及下式的化合物其中Z代表NH; Y代表任选被氨基,一或二(C 1-4烷基)氨基或C 1-4烷氧基羰基氨基 - , - C 3-7烯基-CO-的氨基取代的-C 3-9烷基 - , - C 2-9烯基 - , - 氨基,一或二(C 1-4烷基)氨基 - 或C 1-4烷氧基羰基氨基 - ,C 1-5烷基-NR 13 -C 1-5烷基 - , - C 1-5烷基-NR 14 -CO-C 1-5烷基 - C 1-6烷基-CO-NH - , - C 1-5烷基-CO NR 15 -C 1-5烷基 - , - C 1-3烷基-NH-CO-Het 20 - , - C 1-2烷基-CO-Het 21 -CO-, - C 1-2烷基 -NH-CO-CR16R17-NH-,-C1-2烷基-CO-NH-CR18R19-CO-,-C1-2烷基-CO-NR20-C1-3烷基-CO-或-NR22-CO-C1-3烷基 - NH-; X1表示直接键,O或-O-C 1-2烷基 - ; -X 2表示直接键,-CO-C 1-2烷基 - ,NR 12,-NR 12 -C 1-2烷基 - , - O-N = CH-或-C 1-2烷基 - ; R1和R2是氢或卤素; R3是氢; R4代表氢或C1-4烷氧基; R 12和R 13是氢或C 1-4烷基; R14和R15是氢; R 16和R 17各自独立地表示氢或C 1-4烷基; R 18和R 19是氢或任选被苯基或羟基取代的C 1-4烷基; R 20和R 21是氢或任选被C 1-4烷氧基取代的C 1-4烷基; Het20,Het21和Het22是选自吡咯烷基,2-吡咯烷基或任选被羟基取代的哌啶基的杂环。
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公开(公告)号:US08778920B2
公开(公告)日:2014-07-15
申请号:US12624708
申请日:2009-11-24
申请人: Eddy Jean Edgard Freyne , Peter Jacobus Johannes Antonius Buijnsters , Kristof Van Emelem , Werner Constant Johan Embrechts , Timothy Pietro Suren Perera
发明人: Eddy Jean Edgard Freyne , Peter Jacobus Johannes Antonius Buijnsters , Kristof Van Emelem , Werner Constant Johan Embrechts , Timothy Pietro Suren Perera
IPC分类号: A61K31/33 , C07D487/00 , C07D491/08
CPC分类号: C07D215/54 , A61K31/4748 , C07D498/06
摘要: The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR12—C1-5alkyl-, —C1-6alkyl-NH—CO— or —CO—NH—C1-6alkyl-; X1 represents —O—; X2 represents a direct bond, —NR11—C1-2alkyl-, —NR11—CH2—, —C1-2alkyl-, —O—C1-2alkyl, —O— or —O—CH2—; R1 represents hydrogen or halo; R2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C1-4alkyloxycarbonyl-, Het16-carbonyl- or Ar5; R3 represents hydrogen, hydroxy, C1-4alkyloxy-, Ar4—C1-4alkyloxy or R3 represents C1-4alkyloxy substituted with one or where possible two or more substituents selected from C1-4alkyloxy- or Het2-; R10 represents hydrogen; R11 represents hydrogen, C1-4alkyl- or C1-4alkyl-oxy-carbonyl-; R12 represents Het14-C1-4alkyl, in particular morpholinyl-C1-4alkyl; Het2 represents a heterocycle selected from morpholinyl or piperidinyl optionally substituted with C1-4alkyl-, preferably methyl; Het14 represents morpholinyl; Het16 represents a heterocycle selected from morpholinyl or pyrrolidinyl; Ar4 represents phenyl; Ar5 represents phenyl optionally substituted with cyano.
摘要翻译: 本发明涉及下式的化合物:N-氧化物形式,其药学上可接受的加成盐和立体化学异构形式,其中Z代表NH; Y表示-C3-9烷基,-C1-5烷基-NR12-C1-5烷基,-C 1-6烷基-NH-CO-或-CO-NH-C 1-6烷基; X1表示-O-; X 2表示直接键,-NR 11 -C 1-2烷基 - , - NR 11 -CH 2 - , - C 1-2烷基 - , - O-C 1-2烷基,-O-或-O-CH 2 - 。 R1表示氢或卤素; R 2表示氢,氰基,卤素,羟基羰基 - ,C 1-4烷氧基羰基 - ,Het 16 - 羰基 - 或Ar 5; R 3表示氢,羟基,C 1-4烷氧基 - ,Ar 4 -C 1-4烷氧基或R 3表示被一个或多个可能的两个或多个选自C 1-4烷氧基 - 或Het 2 - 的取代基取代的C 1-4烷氧基; R10表示氢; R11表示氢,C1-4烷基或C1-4烷基 - 氧 - 羰基 - ; R12表示Het14-C1-4烷基,特别是吗啉基-C 1-4烷基; Het2表示选自任选被C 1-4烷基,优选甲基取代的吗啉基或哌啶基的杂环; Het14代表吗啉基; Het16表示选自吗啉基或吡咯烷基的杂环; Ar4表示苯基; Ar 5表示任选被氰基取代的苯基。
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公开(公告)号:US08394786B2
公开(公告)日:2013-03-12
申请号:US12624637
申请日:2009-11-24
申请人: Eddy Jean Edgard Freyne , Timothy Pietro Suren Perera , Peter Jacobus Johannes Antonius Buijnsters , Marc Willems , Gaston Stanislas Marcella Diels , Werner Constant Johan Embrechts , Peter ten Holte , Frederik Jan Rita Rombouts , Carsten Schultz-Fademrecht
发明人: Eddy Jean Edgard Freyne , Timothy Pietro Suren Perera , Peter Jacobus Johannes Antonius Buijnsters , Marc Willems , Gaston Stanislas Marcella Diels , Werner Constant Johan Embrechts , Peter ten Holte , Frederik Jan Rita Rombouts , Carsten Schultz-Fademrecht
IPC分类号: A61K31/33 , C07D487/00
CPC分类号: C07D498/06 , C07C229/16 , C07C229/40 , C07D239/88 , C07D239/93 , C07D239/94
摘要: The present invention concerns the compounds of formula wherein Z represents NH; Y represents —C3-9alkyl-, —C2-9alkenyl-, —C3-7alkyl-CO—NH optionally substituted with amino, mono- or di(C1-4alkyl)amino or C1-4alkyloxycarbonylamino-, —C3-7alkenyl-CO—NH— optionally substituted with amino, mono- or di(C1-4alkyl)amino- or C1-4alkyloxycarbonylamino-, C1-5alkyl-NR13—C1-5alkyl-, —C1-5alkyl-NR14—CO—C1-5alkyl-, —C1-6alkyl-CO—NH—, —C1-5alkyl-CONR15—C1-5alkyl-, —C1-3alkyl-NH—CO-Het20-, —C1-2alkyl-CO-Het21-CO—, —C1-2alkyl-NH—CO—CR16R17—NH—, —C1-2alkyl-CO—NH—CR18R19—CO—, —C1-2alkyl-CO—NR20—C1-3alkyl-CO—, or —NR22—CO—C1-3alkyl-NH—; X1 represents a direct bond, O or —O—C1-2alkyl-; X2 represents a direct bond, —CO—C1-2alkyl-, NR12, —NR12—C1-2alkyl-, —O—N═CH— or —C1-2alkyl-; R1 and R2 are hydrogen or halo; R3 are hydrogen; R4 represents hydrogen or C1-4alkyloxy; R12 and R13 are hydrogen or C1-4alkyl; R14 and R15 are hydrogen; R16 and R17 each independently represent hydrogen or C1-4alkyl; R18 and R19 are hydrogen or C1-4alkyl optionally substituted with phenyl or hydroxy; R20 and R21 are hydrogen or C1-4alkyl optionally substituted with C1-4alkyloxy; Het20, Het21 and Het22 are a heterocycle selected from the group consisting pyrrolidinyl, 2-pyrrolidinonyl or piperidinyl optionally substituted with hydroxy.
摘要翻译: 本发明涉及下式的化合物其中Z代表NH; Y代表任选被氨基,一或二(C 1-4烷基)氨基或C 1-4烷氧基羰基氨基 - , - C 3-7烯基-CO-的氨基取代的-C 3-9烷基 - , - C 2-9烯基 - , - 氨基,一或二(C 1-4烷基)氨基 - 或C 1-4烷氧基羰基氨基 - ,C 1-5烷基-NR 13 -C 1-5烷基 - , - C 1-5烷基-NR 14 -CO-C 1-5烷基 - C 1-6烷基-CO-NH - , - C 1-5烷基-CONR 15 -C 1-5烷基 - , - C 1-3烷基-NH-CO-Het 20 - , - C 1-2烷基-CO-Het 21 -CO-, - C 1-2烷基 - NH-CO-CR16R17-NH-,-C1-2烷基-CO-NH-CR18R19-CO-,-C1-2烷基-CO-NR20-C1-3烷基-CO-或-NR22-CO-C1-3烷基-NH - ; X1表示直接键,O或-O-C 1-2烷基 - ; -X 2表示直接键,-CO-C 1-2烷基 - ,NR 12,-NR 12 -C 1-2烷基 - , - O-N = CH-或-C 1-2烷基 - ; R1和R2是氢或卤素; R3是氢; R4代表氢或C1-4烷氧基; R 12和R 13是氢或C 1-4烷基; R14和R15是氢; R 16和R 17各自独立地表示氢或C 1-4烷基; R 18和R 19是氢或任选被苯基或羟基取代的C 1-4烷基; R 20和R 21是氢或任选被C 1-4烷氧基取代的C 1-4烷基; Het20,Het21和Het22是选自吡咯烷基,2-吡咯烷基或任选被羟基取代的哌啶基的杂环。
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公开(公告)号:US07648975B2
公开(公告)日:2010-01-19
申请号:US10558007
申请日:2004-05-25
申请人: Eddy Jean Edgard Freyne , Timothy Pietro Suren Perera , Peter Jacobus Johannes Antonius Buijnsters , Marc Willems , Gaston Stanislas Marcella Diels , Werner Constant Johan Embrechts
发明人: Eddy Jean Edgard Freyne , Timothy Pietro Suren Perera , Peter Jacobus Johannes Antonius Buijnsters , Marc Willems , Gaston Stanislas Marcella Diels , Werner Constant Johan Embrechts
IPC分类号: A01N43/00 , A61K31/33 , C07D487/00 , C07D491/00 , C07D513/00
CPC分类号: C07D498/06 , C07C229/16 , C07C229/40 , C07D239/88 , C07D239/93 , C07D239/94
摘要: The present invention concerns the compounds of formula (I) the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents O, CH2, NH or S; in particular Z represents NH; Y represents —C3-9alkyl-, —C3-9alkenyl-, —C3-9alkynyl-, —C3-7alkyl-CO—NH— optionally substituted with amino, mono- or di(C1-4alkyl)amino or C1-4 alkyloxycarbonylamino-, —C3-7alkenyl-CO—NH— optionally substituted with amino, mono- or di(C1-4alkyl)amino- or C1-4alkyloxycarbonylamino-, C1-5alkyl-oxy-C1-5alkyl-, —C1-5alkyl NR13—, —C1-5alkyl-, —C1-5alkyl-NR14—CO—C1-5alkyl-, —C1-5alkyl-CO NR15—C1-5alkyl-, —C1-6alkyl-CO—NH—, —C1-6alkyl-NH—CO—, —C1-3alkyl-NH—CS-Het20-, —C1-3alkyl-NH—CO-Het20, —C1-2alkyl-CO-Het21-CO—, -Het22-CH2—CO—NH—C1-3alkyl-, —CO—NH—C1-6alkyl-, —NH—CO—C1-6alkyl-, —CO—C1-7alkyl-, —C1-7alkyl-CO—, —C1-6alkyl-CO—C1-6alkyl-, —C1-2alkyl-NH—CO—CR16R17—NH—, —C1-2alkyl-CO—NH—CR18R19—CO—, —C1-2alkyl-CO—NR20—C1-3alkyl-CO—, C1-2alkyl-NR21—CH2—CO—NH—C1-3alkyl-, or NR22—CO—C1-3alkyl-NH—, X1 represents a direct bond, O or —O—C1-2alkyl-, CO, —CO—C1-2alkyl-, NR11, —NR11—C1-2alkyl-, —CH2—, —O—N═CH— or —C1-2alkyl-; X2 represents a direct bond, O, —O—C1-2alkyl-, CO, —CO—C1-2alkyl-, NR12, —NR12—C1-2alkyl-, —CH2—, —O—N═CH— or —C1-2alkyl-. The growth inhibitory effect anti-tumour activity of the present compounds has been demonstrated in vitro, in enzymatic on the receptor tyrosine kinase EGFR.
摘要翻译: 本发明涉及式(I)化合物的N-氧化物形式,其药学上可接受的加成盐和立体化学异构形式,其中Z代表O,CH2,NH或S; 特别是Z表示NH; 一个或多个(C 1-4烷基)氨基或C 1-4烷氧基羰基氨基 - 取代的C 1-3烷基 - , - C 3-9烯基 - , - C 3-9炔基 - , - 一个或多个(C 1-4烷基)氨基 - 或C 1-4烷氧基羰基氨基 - ,C 1-5烷基 - 氧基-C 1-5烷基 - , - C 1-5烷基NR 13 - , - -C1-5烷基 - , - C 1-5烷基-NR 14 -CO-C 1-5烷基 - , - C 1-5烷基-CO NR 15 -C 1-5烷基 - , - C 1-6烷基-CO-NH-,-C 1-6烷基-NH- CO-,-C 1-3烷基-NH-CS-Het20-,-C1-3烷基-NH-CO-Het20,-C1-2烷基-CO-Het21-CO-,-Het22-CH2-CO-NH-C1-3烷基 - ,-CO-NH-C 1-6烷基 - , - NH-CO-C 1-6烷基 - , - CO-C 1-7烷基 - , - C 1-7烷基-CO-,-C 1-6烷基-CO-C 1-6烷基 - -C1-2烷基-NH-CO-CR16R17-NH-,-C1-2烷基-CO-NH-CR18R19-CO-,-C1-2烷基-CO-NR20-C1-3烷基-CO-,C1-2烷基-NR21- CH2-CO-NH-C1-3烷基 - 或NR22-CO-C1-3烷基-NH-,X1表示直接键,O或-O-C 1-2烷基 - ,CO,-CO-C 1-2烷基 - ,NR 11 ,-NR 11 -C 1-2烷基 - , - CH 2 - ,--ON-CH-或-C 1-2烷基 - ; X2表示直接键合,O,-O-C 1-2烷基 - ,CO,-CO-C 1-2烷基 - ,NR 12,-NR 12 -C 1-2烷基 - , - CH 2 - ,--ON-CH-或-C 1-2烷基 - 。 本发明化合物的生长抑制作用的抗肿瘤活性已在体外证明在酶对受体酪氨酸激酶EGFR的作用。
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公开(公告)号:US07655642B2
公开(公告)日:2010-02-02
申请号:US10596509
申请日:2004-12-15
申请人: Eddy Jean Edgard Freyne , Peter Jacobus Johannes Buijnsters , Kristof Van Emelen , Werner Constant Johan Embrechts , Timothy Pietro Suren Perera
发明人: Eddy Jean Edgard Freyne , Peter Jacobus Johannes Buijnsters , Kristof Van Emelen , Werner Constant Johan Embrechts , Timothy Pietro Suren Perera
IPC分类号: A01N43/00 , A61K31/33 , C07D487/00
CPC分类号: C07D215/54 , A61K31/4748 , C07D498/06
摘要: The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR12—C1-5alkyl-, —C1-6alkyl-NH—CO— or —CO—NH—C1-6alkyl-; X1 represents —O—; X2 represents a direct bond, —NR11—C1-2alkyl-, —NR11—CH2—, —C1-2alkyl-, —O—C1-2alkyl, —O— or —O—CH2—; R1 represents hydrogen or halo; R2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C1-4alkyloxycarbonyl-, Het16-carbonyl- or Ar5; R3 represents hydrogen, hydroxy, C1-4alkyloxy-, Ar4—C1-4alkyloxy or R3 represents C1-4alkyloxy substituted with one or where possible two or more substituents selected from C1-4alkyloxy- or Het2-; R10 represents hydrogen; R11 represents hydrogen, C1-4alkyl- or C1-4alkyl-oxy-carbonyl-; R12 represents Het14-C1-4alkyl, in particular morpholinyl-C1-4alkyl; Het2 represents a heterocycle selected from morpholinyl or piperidinyl optionally substituted with C1-4alkyl-, preferably methyl; Het14 represents morpholinyl; Het16 represents a heterocycle selected from morpholinyl or pyrrolidinyl; Ar4 represents phenyl; Ar5 represents phenyl optionally substituted with cyano.
摘要翻译: 本发明涉及下式的化合物:N-氧化物形式,其药学上可接受的加成盐和立体化学异构形式,其中Z代表NH; Y表示-C3-9烷基,-C1-5烷基-NR12-C1-5烷基,-C 1-6烷基-NH-CO-或-CO-NH-C 1-6烷基; X1表示-O-; X 2表示直接键,-NR 11 -C 1-2烷基 - , - NR 11 -CH 2 - , - C 1-2烷基 - , - O-C 1-2烷基,-O-或-O-CH 2 - 。 R1表示氢或卤素; R 2表示氢,氰基,卤素,羟基羰基 - ,C 1-4烷氧基羰基 - ,Het 16 - 羰基 - 或Ar 5; R 3表示氢,羟基,C 1-4烷氧基 - ,Ar 4 -C 1-4烷氧基或R 3表示被一个或多个可能的两个或多个选自C 1-4烷氧基 - 或Het 2 - 的取代基取代的C 1-4烷氧基; R10表示氢; R11表示氢,C1-4烷基或C1-4烷基 - 氧 - 羰基 - ; R12表示Het14-C1-4烷基,特别是吗啉基-C 1-4烷基; Het2表示选自任选被C 1-4烷基,优选甲基取代的吗啉基或哌啶基的杂环; Het14代表吗啉基; Het16表示选自吗啉基或吡咯烷基的杂环; Ar4表示苯基; Ar 5表示任选被氰基取代的苯基。
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9.
公开(公告)号:US08772272B2
公开(公告)日:2014-07-08
申请号:US12724203
申请日:2010-03-15
申请人: Eddy Jean Edgard Freyne , Marc Willems , Pierre Henri Storck , Virginie Sophie Poncelet , Kristof Van Emelen , Peter Jacobus Johnnes Antonius Buijnsters , Werner Constant Johan Embrechts , Timothy Pietro Suren Perera
发明人: Eddy Jean Edgard Freyne , Marc Willems , Pierre Henri Storck , Virginie Sophie Poncelet , Kristof Van Emelen , Peter Jacobus Johnnes Antonius Buijnsters , Werner Constant Johan Embrechts , Timothy Pietro Suren Perera
IPC分类号: A61K31/33 , A61K31/519 , C07D487/00 , C07D487/18
CPC分类号: C07D498/16 , C07D471/04 , C07D487/04 , C07D487/16 , C07D487/22
摘要: The present invention concerns the compounds of formula the N-oxide forms, the pharmaceutically acceptable addition salts and the stereochemically isomeric forms thereof, wherein a1-a2=a3-a4 represents a divalent radical selected from N—CH═CH—CH, N—CH═N—CH or CH—CH═N—CH; Z represents NH; Y represents —C3-9alkyl-, —C1-5alkyl-NR13—C1-5alkyl-, —C1-6alkyl-NH—CO— or —CO—NH—C1-6alkyl-; X1 represents —O— or —NR11—; X2 represents —C1-2alkyl-, —O—C1-2alkyl, —O— or —O—CH2—; R1 represents hydrogen or halo; R2 represents hydrogen, cyano, halo, hydroxycarbonyl-, C1-4alkyloxycarbonyl-, Het16-carbonyl- or Ar5; R3 represents hydrogen; R4 represents hydroxy, C1-4alkyloxy-, Ar4—C1-4alkyloxy or R4 represents C1-4alkyloxy substituted with one or where possible two or more substituents selected from C1-4alkyloxy- or Het2-; R11 represents hydrogen; R12 represents hydrogen, C1-4alkyl- or C1-4alkyl-oxy-carbonyl-; R13 represents Het14-C1-4alkyl, in particular morpholinyl-C1-4alkyl; Het2 represents a heterocycle selected from morpholinyl or piperidinyl optionally substituted with C1-4alkyl-, preferably methyl; Het14 represents morpholinyl; Het16 represents a heterocycle selected from morpholinyl or pyrrolidinyl; Ar4 represents phenyl; Ar5 represents phenyl optionally substituted with cyano.
摘要翻译: 本发明涉及N-氧化物形式的化合物,其药学上可接受的加成盐和立体化学异构体,其中a1-a2 = a3-a4表示选自N-CH = CH-CH,N- CH = N-CH或CH-CH = N-CH; Z表示NH; Y表示-C3-9烷基 - ,-C1-5烷基-NR13-C1-5烷基 - ,C1-6烷基-NH-CO-或-CO-NH-C1-6烷基 - ; X1表示-O-或-NR11-; X2表示-C1-2烷基 - , - O-C1-2烷基,-O-或-O-CH2-; R1表示氢或卤素; R 2表示氢,氰基,卤素,羟基羰基 - ,C 1-4烷氧基羰基 - ,Het 16 - 羰基 - 或Ar 5; R3表示氢; R 4表示羟基,C 1-4烷氧基 - ,Ar 4 -C 1-4烷氧基或R 4表示被一个或多个可能的两个或多个选自C 1-4烷氧基或Het 2-的取代基取代的C 1-4烷氧基; R11表示氢; R 12表示氢,C 1-4烷基 - 或C 1-4烷基 - 氧基 - 羰基 - ; R13表示Het14-C1-4烷基,特别是吗啉基-C 1-4烷基; Het2表示选自任选被C 1-4烷基,优选甲基取代的吗啉基或哌啶基的杂环; Het14代表吗啉基; Het16表示选自吗啉基或吡咯烷基的杂环; Ar4表示苯基; Ar 5表示任选被氰基取代的苯基。
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公开(公告)号:US08895601B2
公开(公告)日:2014-11-25
申请号:US13643741
申请日:2011-04-28
申请人: Gordon Saxty , Christopher William Murray , Valerio Berdini , Gilbert Ebai Besong , Christopher Charles Frederick Hamlett , Christopher Norbert Johnson , Steven John Woodhead , David Charles Rees , Laurence Anne Mevellec , Patrick René Angibaud , Eddy Jean Edgard Freyne , Timothy Pietro Suren Perera , Ronaldus Arnodus Hendrika Joseph Gilissen , Berthold Wroblowski , Jean Fernand Armand Lacrampe , Alexandra Papanikos , Oliver Alexis Georges Querolle , Elisabeth Thérèse Jeanne Pasquier , Isabelle Noëlle Constance Pilatte , Pascal Ghislain André Bonnet , Werner Constant Johan Embrechts , Rhalid Akkari , Lieven Meerpoel
发明人: Gordon Saxty , Christopher William Murray , Valerio Berdini , Gilbert Ebai Besong , Christopher Charles Frederick Hamlett , Christopher Norbert Johnson , Steven John Woodhead , David Charles Rees , Laurence Anne Mevellec , Patrick René Angibaud , Eddy Jean Edgard Freyne , Timothy Pietro Suren Perera , Ronaldus Arnodus Hendrika Joseph Gilissen , Berthold Wroblowski , Jean Fernand Armand Lacrampe , Alexandra Papanikos , Oliver Alexis Georges Querolle , Elisabeth Thérèse Jeanne Pasquier , Isabelle Noëlle Constance Pilatte , Pascal Ghislain André Bonnet , Werner Constant Johan Embrechts , Rhalid Akkari , Lieven Meerpoel
IPC分类号: A61K31/415 , C07D231/10 , C07D231/12 , C07D405/14 , C07D403/04 , C07D487/08 , C07D413/14 , C07D403/14 , C07D409/14
CPC分类号: C07D403/04 , A61K31/498 , A61K31/5377 , A61K45/06 , C07D401/14 , C07D403/14 , C07D405/14 , C07D409/14 , C07D413/14 , C07D487/08 , C07D491/113 , C07F9/6524
摘要: The invention relates to new quinoxaline derivative compounds, to pharmaceutical compositions comprising said compounds, to processes for the preparation of said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.
摘要翻译: 本发明涉及新的喹喔啉衍生物化合物,包含所述化合物的药物组合物,用于制备所述化合物的方法和所述化合物在治疗疾病中的用途。 癌症。
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