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公开(公告)号:WO2016202412A1
公开(公告)日:2016-12-22
申请号:PCT/EP2015074491
申请日:2015-10-22
Applicant: UCB BIOPHARMA SPRL
Inventor: O'CONNELL JAMES PHILIP , PORTER JOHN ROBERT , LAWSON ALASTAIR , KROEPLIEN BORIS , RAPECKI STEPHEN EDWARD , NORMAN TIMOTHY JOHN , WARRELLOW GRAHAM JOHN , ARAKAKI TRACY LYNN , BURGIN ALEX BUNTIN , PITT WILLIAM ROSS , CALMIANO MARK DANIEL , SCHUBERT DAVID ANDREAS , LIGHTWOOD DANIEL JOHN , WOOTTON REBECCA JAYNE
IPC: G01N33/68 , C07D401/14 , C07D471/00 , C07K14/525 , C07K14/705
CPC classification number: G01N33/6845 , C07D401/14 , C07D471/00 , C07K14/525 , C07K14/70575 , C07K16/241 , G01N2500/02
Abstract: A new, stable trimeric TNFα structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNFα/TNFR1 interaction. Membrane-bound TNFα is not affected in its ability to signal through TNFR2, and thus the new structure of TNFα may be used in therapies which do not significantly raise the risk of infection or malignancy.
Abstract translation: 公开了一种新的稳定的三聚体TNFα结构,其具有扭曲的对称性,其可以结合TNFR1受体以减弱其信号传导,其可用于治疗和/或预防与可溶性TNFα/ TNFR1相互作用相关的疾病。 膜结合的TNFα在其通过TNFR2信号的能力方面不受影响,因此TNFα的新结构可用于不显着升高感染或恶性肿瘤风险的疗法。
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公开(公告)号:MX380578B
公开(公告)日:2025-03-12
申请号:MX2017004201
申请日:2017-03-30
Applicant: UCB BIOPHARMA SPRL , SANOFI SA
Inventor: FILOCHE-ROMME BRUNO , BROOKINGS DANIEL CHRISTOPHER , LÉON SWINNEN DOMINIQUE LOUIS , HEER JAG PAUL , JOHNSON JAMES ANDREW , KEYAERTS JEAN , QUINCEY JOANNA RACHEL , SCHIO LAURENT , COSS MALCOLM MAC , CALMIANO MARK DANIEL , HUTCHINGS MARTIN CLIVE , SELBY MATTHEW DUNCAN , XUAN MENGYANG , SHAW MICHAEL ALAN , DELIGNY MICHAEL , JADOT SOPHIE , DE HARO GARCIA TERESA , FORICHER YANN , EVRARD YVES , ZHU ZHAONING
IPC: C07D471/18 , A61K31/4188 , A61P3/00 , A61P9/00 , A61P25/00 , A61P29/00 , A61P35/00 , C07D487/18 , C07D493/18
Abstract: Una serie de derivados de imidazol pentacíclicos fusionados, que son potentes moduladores de la actividad de TNFa humano, son en consecuencia beneficiosos en el tratamiento y/o prevención de diferentes enfermedades humanas, que incluyen trastornos autoinmunológicos e inflamatorios; trastornos neurológicos y neurodegenerativos; trastornos de dolor y nociceptivos; trastornos cardiovasculares; trastornos metabólicos; trastornos oculares; y trastornos oncológicos. En particular, la presente invención se relaciona con derivados de 6,7-dihidro-7,14-metanobencimidazo[1,2-b] [2,5]benzodiazocin-5(14H)-ona y análogos de los mismos.
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公开(公告)号:ES2885432T3
公开(公告)日:2021-12-13
申请号:ES15771976
申请日:2015-10-02
Applicant: UCB BIOPHARMA SPRL , SANOFI SA
Inventor: DE HARO GARCIA TERESA , DELIGNY MICHAEL , HEER JAG PAUL , QUINCEY JOANNA RACHEL , XUAN MENGYANG , ZHU ZHAONING , BROOKINGS DANIEL CHRISTOPHER , CALMIANO MARK DANIEL , EVRARD YVES , HUTCHINGS MARTIN CLIVE , JOHNSON JAMES ANDREW , JADOT SOPHIE , KEYAERTS JEAN , MAC COSS MALCOLM , SELBY MATTHEW DUNCAN , SHAW MICHAEL ALAN , SWINNEN DOMINIQUE LOUIS LÉON , SCHIO LAURENT , FORICHER YANN , FILOCHE-ROMME BRUNO
IPC: C07D491/08 , A61K31/55 , A61P3/00 , A61P9/00 , A61P25/00 , A61P27/00 , A61P35/00 , A61P37/00 , A61P43/00 , C07D471/18 , C07D487/08 , C07D491/18 , C07D493/18 , C07D495/08 , C07D495/18 , C07D513/18 , C07D519/00 , C07F7/18
Abstract: Un compuesto de fórmula (I) o un N-óxido del mismo o una sal farmacéuticamente aceptable del mismo, **(Ver fórmula)** en donde -X-Q- representa -O-, -O-C(O)-, -O-C(CH-CN)-, -S-, -SO-, -SO2-; o -N(Rg)-, - N(Rf)-CO-, -N(Rf)-SO2-, -O-CH2-, - CH2-S-, -CH2-SO-, -CH2-SO2-, -N(Rg)-CH2-, -N(Rf)-C(S)-, -N=S(O)(CH3)-, -O-C(=CH2)- o -S(=N-CN)-, cualquiera de tales grupos puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, alquilo (C1-6), carboxi, trifluorometilo, alquilcarbonilo (C2-6), alcoxicarbonilo (C2-6) e hidroxialquilo (C1-6); Z representa metileno; E representa un sistema de anillo heteroaromático condensado seleccionado entre los grupos de fórmula (Ea) y (Eb), en donde el asterisco (*) representa el sitio de unión de E al resto de la molécula; R1 representa halógeno o ciano; o arilo, heteroarilo, cicloalquil (C3-7)-heteroarilo, heterocicloalquil (C3-7)-heteroarilo, heterobicicloalquil (C4-9)-heteroarilo, heterocicloalquilo (C3-7), heterocicloalquenilo (C3-7) o heterocicloalquenil (C3- 7)-arilo, cualquiera de tales grupos puede estar opcionalmente sustituido con uno, dos o tres sustituyentes seleccionados entre halógeno, ciano, cianoalquilo (C1-6), alquilo C1-6, difluorometilo, trifluorometilo, hidroxi, (hidroxi)alquilo (C1-6), amino, (amino)alquilo (C1-6), alcoxi C1-6, alcoxi (C1-6)alquilo (C1-6), alquilcarbonilo C2-6, alcoxicarbonilo C2-6, alcoxicarbonil (C2-6)-amino-alquilo C1-6, fosfatoalquilo (C1-6), alquiltio C1-6, alquilsulfonilo C1-6, oxo, alquilsulfoximinilo (C1-6), alquilsulfinil (C1-6)-amino-, dialquilamino (C1-6)alquilo (C1-6), alquilcarbonilamino (C2- 6)-alquilo (C1-6), dialquenilamino (C1-6)alquilo (C1-6), alquilcarbonilamino (C2-6)-alquilo (C1-6), alquilsulfonil C1-6- amino-alquilo C1-6, tetrahidrofuranilo, sulfatoalquilo (C1-6) y carboxi-alquil (C1-6)-carboniloxi-alquilo (C1-6); R2 representa hidrógeno o halógeno; R3 representa hidrógeno o trifluorometilo; R4 representa hidrógeno o trifluorometilo; R5 representa halógeno, -ORa, difluorometoxi o trifluorometoxi; R6 representa hidrógeno, halógeno o trifluorometilo; R7 representa hidrógeno o trifluorometilo; R8 representa hidrógeno, halógeno o trifluorometilo; R12 representa hidrógeno o alquilo C1-6; Ra representa alquilo C1-6; Rf representa hidrógeno; o alquilo C1-6, grupo que puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre trifluorometilo, carboxi e hidroxi; y Rg representa hidrógeno; o alquilo C1-6, -CO-alquilo (C1-6), -SO2-alquilo (C1-6), -CO-heterocicloalquilo (C3-7), -SO2- cicloalquilo (C3-7), -SO2-arilo, -SO2-heteroarilo, heteroarilo o alcoxicarbonilo (C2-6), cualquiera de tales grupos puede estar opcionalmente sustituido con uno o más sustituyentes seleccionados entre halógeno, alquilo C1-6, carboxi, alcoxicarbonilo C1-6, trifluorometilo, heterobicicloalquilo C4-9, (alquil C1-6)-sulfonilo, tri(alquil C1-6)sililoxi, hidroxi y alcoxi (C1-6).
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公开(公告)号:ECSP17027306A
公开(公告)日:2017-05-31
申请号:ECPI201727306
申请日:2017-05-03
Applicant: UCB BIOPHARMA SPRL , SANOFI SA
Inventor: THE COCA-COLA COMPANY , CALMIANO MARK DANIEL , BROOKINGS DANIEL CHRISTOPHER , ZHU ZHAONING , SHELBY GROUP INTERNATIONAL INC , SELBY MATTHEW DUNCAN , MAC COSS MALCOM , JOHNSON JAMES ANDREW , JADOT SOPHIE , HUTCHINGS MARTIN CLIVE , MICROSOFT CORPORATION , SHAW MICHAEL ALAN , FORICHER YANN , SCHIO LAURENT , XUAN MENGYANG , FILOCHE-ROMME BRUNO , MILLER BREWING INTERNATIONAL INC , HEER JAG PAUL , KEYAERTS JEAN , DE HARO GARCIA TERESA
IPC: C07D471/18 , A61K31/4188 , A61P3/00 , A61P9/00 , A61P25/00 , A61P29/00 , A61P35/00 , C07D487/18 , C07D493/18
Abstract: Una serie de derivados de imidazol pentacíclicos fusionados, que son potentes moduladores de la actividad de TNFα humano, son en consecuencia beneficiosos en el tratamiento y/o prevención de diferentes enfermedades humanas, que incluyen trastornos autoinmunológicos e inflamatorios; trastornos neurológicos y neurodegenerativos; trastornos de dolor y nociceptivos; trastornos cardiovasculares; trastornos metabólicos; trastornos oculares; y trastornos oncológicos. En particular, la presente invención se relaciona con derivados de 6,7-dihidro-7,14-metanobencimidazo[1,2-b][2,5]benzodiazocin-5(14H)-ona y análogos de los mismos.
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公开(公告)号:AP201709809A0
公开(公告)日:2017-03-31
申请号:AP201709809
申请日:2015-10-02
Applicant: UCB BIOPHARMA SPRL , SANOFI SA
Inventor: DE HARO GARCIA TERESA , DELIGNY MICHAEL , HEER JAG PAUL , QUINCEY JOANNA RACHEL , XUAN MENGYANG , ZHU ZHAONING , BROOKINGS DANIEL CHRISTOPHER , CALMIANO MARK DANIEL , EVRARD YVES , HUTCHINGS MARTIN CLIVE , JOHNSON JAMES ANDREW , JADOT SOPHIE , KEYAERTS JEAN , MAC COSS MALCOLM , SELBY MATTHEW DUNCAN , SHAW MICHAEL ALAN , SWINNEN DOMINIQUE LOUIS LÉON , SCHIO LAURENT , FORICHER YANN , FILOCHE-ROMME BRUNO
IPC: A61P35/00 , A61K31/4188 , A61P3/00 , A61P9/00 , A61P25/00 , A61P29/00 , C07D471/18 , C07D487/18 , C07D493/18
CPC classification number: C07D519/00 , A61K31/4184 , A61K31/506 , A61K31/55 , C07D471/18 , C07D487/08 , C07D487/18 , C07D491/08 , C07D491/18 , C07D493/18 , C07D495/08 , C07D495/18 , C07D513/18 , C07F7/1852
Abstract: A series of fused pentacyclic imidazole derivatives, being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders. In particular, the present invention is concerned with 6,7-dihydro-7,14-methanobenzimidazo[1,2-b][2,5]benzodiazocin-5(14H)-one derivatives and analogs thereof.
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公开(公告)号:CA2931758C
公开(公告)日:2022-10-25
申请号:CA2931758
申请日:2014-12-08
Applicant: UCB BIOPHARMA SPRL
Inventor: ALEXANDER RIKKI PETER , BRACE GARETH NEIL , BROWN JULIEN ALISTAIR , CALMIANO MARK DANIEL , CHOVATIA PRAFUL TULSHI , DELIGNY MICHAEL , GALLIMORE ELLEN OLIVIA , HEER JAG PAUL , JACKSON VICTORIA ELIZABETH , KROEPLIEN BORIS , MAC COSS MALCOLM , QUINCEY JOANNA RACHEL , SABNIS YOGESH ANIL , SWINNEN DOMINIQUE LOUIS LEON , ZHU ZHAONING , WEHNER VOLMAR , HEINELT UWE
IPC: C07D471/04 , A61K31/437 , C07D519/00
Abstract: Compounds of formula (I) or N-oxides thereof, or pharmaceutically acceptable salts or solvates thereof, or glucuronide derivatives thereof, or co-crystals thereof, including a compound represented by formula (IIA), or an N-oxide thereof, or a pharmaceutically acceptable salt or solvate thereof, being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders.
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公开(公告)号:PE20170693A1
公开(公告)日:2017-06-13
申请号:PE2017000544
申请日:2015-10-02
Applicant: UCB BIOPHARMA SPRL , SANOFI SA
Inventor: DE HARO GARCIA TERESA , DELIGNY MICHAEL , HEER JAG PAUL , QUINCEY JOANNA RACHEL , XUAN MENGYANG , ZHU ZHAONING , BROOKINGS DANIEL CHRISTOPHER , CALMIANO MARK DANIEL , EVRARD YVES , HUTCHINGS MARTIN CLIVE , JOHNSON JAMES ANDREW , JADOT SOPHIE , KEYAERTS JEAN , MAC COSS MALCOLM , SELBY MATTHEW DUNCAN , SHAW MICHAEL ALAN , SWINNEN DOMINIQUE LOUIS LEON , SCHIO LAURENT , FORICHER YANN , FILOCHE-ROMME BRUNO
IPC: C07D471/18 , A61K31/4188 , A61P3/00 , A61P9/00 , A61P25/00 , A61P29/00 , A61P35/00 , C07D487/18 , C07D493/18
Abstract: SE REFIERE A COMPUESTOS DERIVADOS DE IMIDAZOL PENTACICLICOS FUSIONADOS DE FORMULA (I) DONDE -X-Q- REPRESENTA -O-, -O-C(O)-, -C(O)-O-, ENTRE OTROS; Z ES METILENO; E ES 1H-BENZIMIDAZOL, IMIDAZO[1,2-a]PIRIDINA O IMIDAZO[1,2-a]PIRAZINA OPCIONALMENTE SUSTITUIDOS; R5 Y R8 SON CADA UNO H, HALOGENO, HIDROXI, CN, ENTRE OTROS; R6 Y R7 SON CADA UNO H, HALOGENO, TRIFLUOROMETILO, ENTRE OTROS; R12 ES H O C1-C6 ALQUILO. SON COMPUESTOS PREFERIDOS: (7R,14R)-1-(DIFLUOROMETOXI)-10-FLUORO-11-[2-(2-HIDROXIPROPAN-2-IL)PIRIMIDIN-5-IL]-6,7-DIHIDRO-7,14-METANOBENCIMIDAZO[1,2-b][2,5]BENZODIAZOCIN-5(14H)-ONA; (7R,14R)-1-(DIFLUOROMETOXI)-11-[2-(2-HIDROXIPROPAN-2-IL)PIRIMIDIN-5-IL]-6,7-DIHIDRO-7,14-METANOBENCIMIDAZO[1,2-b][2,5]BENZODIAZOCIN-5(14H)-ONA; ENTRE OTROS. DICHOS COMPUESTOS SON MODULADORES DE LA ACTIVIDAD DE TNF ALFA HUMANO SIENDO UTILES EN EL TRATAMIENTO DE TRASTORNOS INFLAMATORIOS, TRASTORNOS NEUROLOGICOS Y NEURODEGENERATIVOS
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公开(公告)号:SG11201701796XA
公开(公告)日:2017-04-27
申请号:SG11201701796X
申请日:2015-10-02
Applicant: UCB BIOPHARMA SPRL , SANOFI SA
Inventor: DE HARO GARCIA TERESA , DELIGNY MICHAEL , HEER JAG PAUL , QUINCEY JOANNA RACHEL , XUAN MENGYANG , ZHU ZHAONING , BROOKINGS DANIEL CHRISTOPHER , CALMIANO MARK DANIEL , EVRARD YVES , HUTCHINGS MARTIN CLIVE , JOHNSON JAMES ANDREW , JADOT SOPHIE , KEYAERTS JEAN , MAC COSS MALCOLM , SELBY MATTHEW DUNCAN , SHAW MICHAEL ALAN , SWINNEN DOMINIQUE LOUIS LÉON , SCHIO LAURENT , FORICHER YANN , FILOCHE-ROMME BRUNO
IPC: C07D471/18 , A61K31/4188 , A61P3/00 , A61P9/00 , A61P25/00 , A61P29/00 , A61P35/00 , C07D487/18 , C07D493/18
Abstract: A series of fused pentacyclic imidazole derivatives, being potent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders. In particular, the present invention is concerned with 6,7-dihydro-7,14-methanobenzimidazo[1,2-b][2,5]benzodiazocin-5(14H)-one derivatives and analogs thereof.
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公开(公告)号:CA2988516A1
公开(公告)日:2016-12-22
申请号:CA2988516
申请日:2015-10-22
Applicant: UCB BIOPHARMA SPRL
Inventor: O'CONNELL JAMES PHILIP , PORTER JOHN ROBERT , LAWSON ALASTAIR , KROEPLIEN BORIS , RAPECKI STEPHEN EDWARD , NORMAN TIMOTHY JOHN , WARRELLOW GRAHAM JOHN , ARAKAKI TRACY LYNN , BURGIN ALEX BUNTIN , PITT WILLIAM ROSS , CALMIANO MARK DANIEL , SCHUBERT DAVID ANDREAS , LIGHTWOOD DANIEL JOHN , WOOTTON REBECCA JAYNE
IPC: G01N33/68 , C07D401/14 , C07D471/00 , C07K14/525 , C07K14/705
Abstract: A new, stable trimeric TNFa structure is disclosed with distorted symmetry which can bind to the TNFR1 receptor to attenuate signalling therefrom, which can be used in the treatment and/or prevention of diseases associated with the soluble TNFa/TNFR1 interaction. Membrane-bound TNFa is not affected in its ability to signal through TNFR2, and thus the new structure of TNFa may be used in therapies which do not significantly raise the risk of infection or malignancy.
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公开(公告)号:CA2962826A1
公开(公告)日:2016-04-07
申请号:CA2962826
申请日:2015-10-02
Applicant: SANOFI SA , UCB BIOPHARMA SPRL
Inventor: DE HARO GARCIA TERESA , DELIGNY MICHAEL , HEER JAG PAUL , QUINCEY JOANNA RACHEL , XUAN MENGYANG , ZHU ZHAONING , BROOKINGS DANIEL CHRISTOPHER , CALMIANO MARK DANIEL , EVRARD YVES , HUTCHINGS MARTIN CLIVE , JOHNSON JAMES ANDREW , JADOT SOPHIE , KEYAERTS JEAN , MAC COSS MALCOLM , SELBY MATTHEW DUNCAN , SHAW MICHAEL ALAN , SWINNEN DOMINIQUE LOUIS LEON , SCHIO LAURENT , FORICHER YANN , FILOCHE-ROMME BRUNO
IPC: C07D471/18 , A61K31/4188 , A61P3/00 , A61P9/00 , A61P25/00 , A61P29/00 , A61P35/00 , C07D487/18 , C07D493/18
Abstract: The present invention relates to a series of fused pentacyclic imidazole derivatives which, being patent modulators of human TNFa activity, are accordingly of benefit in the treatment and/or prevention of various human ailments, including autoimmune and inflammatory disorders; neurological and neurodegenerative disorders; pain and nociceptive disorders; cardiovascular disorders; metabolic disorders; ocular disorders; and oncological disorders. In particular, the present invention is concemed with 6, 7-dihydro-7,l 4-methanobenzimidazo[l ,2-b] [2,5]benzodiazocin- 5(14H)-one derivatives and analogs thereof, and more particularly a compound of formula (I) or an N-oxide thereof, or a pharmaceutically acceptable salt thereof.
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