公开(公告)号：US10118895B2

公开(公告)日：2018-11-06

申请号：US15578997

申请日：2016-06-03

申请人： LEAD PHARMA HOLDING B.V. ,  SANOFI

发明人： Joseph Maria Gerardus Barbara Cals ,  David Machnik ,  Sander Bernardus Nabuurs ,  Jean-Francois Sabuco ,  Laurent Schio

IPC分类号： C07D213/71 ,  C07D237/18 ,  C07D239/38 ,  C07D405/12 ,  A61K31/44 ,  A61K31/4965 ,  A61K31/50 ,  A61K31/444 ,  A61K31/4427 ,  A61K31/505 ,  C07D241/18

摘要： Novel compounds according to Formula I Meta or para or a pharmaceutically acceptable salt thereof wherein: A11-A14 are N or CR11, CR12, CR13, CR14, respectively, with the proviso that no more than two of the four positions A in A11-A14 can be simultaneously N; A6, A7, A8, A9, A10 are N or CR6, CR7, CR8, CR9, CR10, respectively, with the proviso that at least one but no more than two of the five positions A in A6, A7, A8, A9, A10 is N; R1 is C(2-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, (di)C(3-6)cycloalkylamino or (di)(C(3-6)cycloalkylC(1-3)alkyl)amino; R5 is H, hydroxyethyl, methoxyethyl, C(1-6)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkylC(1-3)alkyl; the sulfonyl group with R1 is represented by one of R7, R8 or R9; R15 is H, C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl; and R16 is C(1-6)alkyl, C(3-6)cycloalkyl, C(3-6)cycloalkylC(1-3)alkyl, C(6-10)aryl, C(6-10)arylC(1-3)alkyl, C(1-9)heteroaryl, C(1-9)heteroarylC(1-3)alkyl, C(2-5)heterocycloalkyl or C(2-5)heterocycloalkyl-C(1-3)alkyl.

公开(公告)号：US20170305932A1

公开(公告)日：2017-10-26

申请号：US15513357

申请日：2015-10-02

申请人： UCB Biopharma SPRL ,  Sanofi

发明人： Teresa De Haro Garcia ,  Michael Deligny ,  Jag Paul Heer ,  Joanna Rachel Quincey ,  Mengyang Xuan ,  Zhaoning Zhu ,  Daniel Christopher Brookings ,  Mark Daniel Calmiano ,  Yves Evrard ,  Martin Clive Hutchings ,  James Andrew Johnson ,  Sophie Jadot ,  Jean Keyaerts ,  Malcolm Mac Coss ,  Matthew Duncan Selby ,  Michael Alan Shaw ,  Dominique Louis Leon Swinnen ,  Laurent Schio ,  Yann Foricher ,  Bruno Filoche-Romme

IPC分类号： C07D519/00 ,  C07D495/18 ,  C07D487/18 ,  C07D491/18 ,  C07F7/18 ,  C07D513/18

CPC分类号： 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 ,  C07F7/1804

摘要： 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.

公开(公告)号：US09714221B1

公开(公告)日：2017-07-25

申请号：US15432470

申请日：2017-02-14

申请人： Sanofi

发明人： Monsif Bouaboula ,  Maurice Brollo ,  Victor Certal ,  Youssef El-Ahmad ,  Bruno Filoche-Romme ,  Frank Halley ,  Gary McCort ,  Laurent Schio ,  Michel Tabart ,  Corinne Terrier ,  Fabienne Thompson

IPC分类号： C07D207/12 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  A61K31/4025 ,  A61K31/341 ,  A61K31/351 ,  C07D471/04 ,  C07D413/12 ,  C07F7/08 ,  C07D417/12

CPC分类号： C07D207/12 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  C07F7/0812

摘要： Compounds of formula (I): wherein R1 and R2 represent hydrogen or deuterium atoms; R3 represents a hydrogen atom or a —COOH, a —OH or a —OPO(OH)2 group; R4 represents a hydrogen atom or a fluorine atom; R5 represents a hydrogen atom or a —OH group; wherein at least one of R3 or R5 is different from a hydrogen atom; when R3 represents a —COOH, —OH or —OPO(OH)2 group, then R5 represents a hydrogen atom; when R5 represents a —OH group, then R3 and R4 represent hydrogen atoms; and R6 is selected from an optionally substituted phenyl, heteroaryl, cycloalkyl and heterocycloalkyl group; and the preparation and the therapeutic uses of the compounds of formula (I) as inhibitors and degraders of estrogen receptors, useful especially in the treatment of cancer.

公开(公告)号：US10202405B2

公开(公告)日：2019-02-12

申请号：US15513357

申请日：2015-10-02

申请人： UCB Biopharma SPRL ,  Sanofi

发明人： Teresa De Haro Garcia ,  Michael Deligny ,  Jag Paul Heer ,  Joanna Rachel Quincey ,  Mengyang Xuan ,  Zhaoning Zhu ,  Daniel Christopher Brookings ,  Mark Daniel Calmiano ,  Yves Evrard ,  Martin Clive Hutchings ,  James Andrew Johnson ,  Sophie Jadot ,  Jean Keyaerts ,  Malcolm Mac Coss ,  Matthew Duncan Selby ,  Michael Alan Shaw ,  Dominique Louis Leon Swinnen ,  Laurent Schio ,  Yann Foricher ,  Bruno Filoche-Romme

IPC分类号： C07D519/00 ,  C07F7/18 ,  C07D471/18 ,  C07D487/18 ,  C07D493/18 ,  C07D491/08 ,  A61K31/4184 ,  A61K31/506 ,  A61K31/55 ,  C07D487/08 ,  C07D491/18 ,  C07D495/08 ,  C07D495/18 ,  C07D513/18

摘要： 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.

公开(公告)号：US11912721B2

公开(公告)日：2024-02-27

申请号：US17102790

申请日：2020-11-24

申请人： UCB Biopharma SRL ,  Sanofi

发明人： Teresa De Haro Garcia ,  Michael Deligny ,  Jag Paul Heer ,  Joanna Rachel Quincey ,  Mengyang Xuan ,  Zhaoning Zhu ,  Daniel Christopher Brookings ,  Mark Daniel Calmiano ,  Yves Evrard ,  Martin Clive Hutchings ,  James Andrew Johnson ,  Sophie Jadot ,  Jean Keyaerts ,  Malcolm MacCoss ,  Matthew Duncan Selby ,  Michael Alan Shaw ,  Dominique Louis Leon Swinnen ,  Laurent Schio ,  Yann Foricher ,  Bruno Filoche-Romme

IPC分类号： C07D519/00 ,  C07D491/08 ,  C07D487/08 ,  C07D491/18 ,  C07D495/08 ,  C07D471/18 ,  C07D487/18 ,  C07D493/18 ,  C07D495/18 ,  C07D513/18 ,  C07F7/18 ,  A61K31/4184 ,  A61K31/506 ,  A61K31/55

CPC分类号： 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 ,  C07F7/1804

摘要： 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.

公开(公告)号：US20210155637A1

公开(公告)日：2021-05-27

申请号：US17102790

申请日：2020-11-24

申请人： UCB Biopharma SRL ,  Sanofi

发明人： Teresa De Haro Garcia ,  Michael Deligny ,  Jag Paul Heer ,  Joanna Rachel Quincey ,  Mengyang Xuan ,  Zhaoning Zhu ,  Daniel Christopher Brookings ,  Mark Daniel Calmiano ,  Yves Evrard ,  Martin Clive Hutchings ,  James Andrew Johnson ,  Sophie Jadot ,  Jean Keyaerts ,  Malcolm Mac Coss ,  Matthew Duncan Selby ,  Michael Alan Shaw ,  Dominique Louis Leon Swinnen ,  Laurent Schio ,  Yann Foricher ,  Bruno Filoche-Romme

IPC分类号： C07D519/00 ,  C07F7/18 ,  C07D491/08 ,  A61K31/4184 ,  A61K31/506 ,  A61K31/55 ,  C07D487/08 ,  C07D491/18 ,  C07D495/08 ,  C07D471/18 ,  C07D487/18 ,  C07D493/18 ,  C07D495/18 ,  C07D513/18

摘要： 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.

公开(公告)号：US11214541B2

公开(公告)日：2022-01-04

申请号：US17124852

申请日：2020-12-17

申请人： SANOFI

发明人： Monsif Bouaboula ,  Maurice Brollo ,  Victor Certal ,  Youssef El-Ahmad ,  Bruno Filoche-Romme ,  Frank Halley ,  Gary Mccort ,  Laurent Schio ,  Michel Tabart ,  Corinne Terrier ,  Fabienne Thompson

IPC分类号： C07D207/12 ,  C07D403/12 ,  C07D401/12 ,  C07D471/04 ,  C07D405/12 ,  C07D413/12 ,  C07F7/08 ,  C07D417/12 ,  C07F5/02

摘要： Compounds of formula (I): wherein R1 and R2 represent hydrogen or deuterium atoms; R3 represents a hydrogen atom or a —COOH, a —OH or a —OPO(OH)2 group; R4 represents a hydrogen atom or a fluorine atom; R5 represents a hydrogen atom or a —OH group; wherein at least one of R3 or R5 is different from a hydrogen atom; when R3 represents a —COOH, —OH or —OPO(OH)2 group, then R5 represents a hydrogen atom; when R5 represents a —OH group, then R3 and R4 represent hydrogen atoms; and R6 is selected from an optionally substituted phenyl, heteroaryl, cycloalkyl and heterocycloalkyl group; and the preparation and the therapeutic uses of the compounds of formula (I) as inhibitors and degraders of estrogen receptors, useful especially in the treatment of cancer.

公开(公告)号：US11149031B2

公开(公告)日：2021-10-19

申请号：US16414558

申请日：2019-05-16

申请人： SANOFI

发明人： Monsif Bouaboula ,  Maurice Brollo ,  Victor Certal ,  Youssef El-Ahmad ,  Bruno Filoche-Romme ,  Frank Halley ,  Gary McCort ,  Laurent Schio ,  Michel Tabart ,  Corinne Terrier ,  Fabienne Thompson

IPC分类号： A61P15/00 ,  A61P19/10 ,  A61P35/00 ,  C07D207/12 ,  C07D409/12 ,  C07D405/12

摘要： The present disclosure relates to novel substituted N-(3-fluoropropyl)-pyrrolidine compounds of formula (I-A), wherein R1 and R2 represent independently a hydrogen atom or a deuterium atom; A represents an oxygen or nitrogen atom; and SERM-F represents a selective estrogen receptor modulator fragment comprising an aryl or heteroaryl group linked to the adjacent “A” group. The disclosure also relates to the preparation and to the therapeutic uses of the compounds of formula (I-A) as inhibitors and degraders of estrogen receptors.

公开(公告)号：US10906919B2

公开(公告)日：2021-02-02

申请号：US16220847

申请日：2018-12-14

申请人： UCB Biopharma SRL ,  Sanofi

发明人： Teresa De Haro Garcia ,  Michael Deligny ,  Jag Paul Heer ,  Joanna Rachel Quincey ,  Mengyang Xuan ,  Zhaoning Zhu ,  Daniel Christopher Brookings ,  Mark Daniel Calmiano ,  Yves Evrard ,  Martin Clive Hutchings ,  James Andrew Johnson ,  Sophie Jadot ,  Jean Keyaerts ,  Malcolm Mac Coss ,  Matthew Duncan Selby ,  Michael Alan Shaw ,  Dominique Louis Leon Swinnen ,  Laurent Schio ,  Yann Foricher ,  Bruno Filoche-Romme

IPC分类号： C07D519/00 ,  C07F7/18 ,  C07D491/08 ,  A61K31/4184 ,  A61K31/506 ,  A61K31/55 ,  C07D487/08 ,  C07D491/18 ,  C07D495/08 ,  C07D471/18 ,  C07D487/18 ,  C07D493/18 ,  C07D495/18 ,  C07D513/18

摘要： 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.

公开(公告)号：US10570090B2

公开(公告)日：2020-02-25

申请号：US15613689

申请日：2017-06-05

申请人： SANOFI

发明人： Monsif Bouaboula ,  Maurice Brollo ,  Victor Certal ,  Youssef El-Ahmad ,  Bruno Filoche-Romme ,  Frank Halley ,  Gary McCort ,  Laurent Schio ,  Michel Tabart ,  Corinne Terrier ,  Fabienne Thompson

IPC分类号： A61K31/40 ,  A61K31/025 ,  C07C13/32 ,  C07C22/08 ,  C07D207/12 ,  C07D403/12 ,  C07D401/12 ,  C07D471/04 ,  C07D405/12 ,  C07D413/12 ,  C07F7/08 ,  C07D417/12 ,  C07F5/02

摘要： Compounds of formula (I): wherein R1 and R2 represent hydrogen or deuterium atoms; R3 represents a hydrogen atom or a —COOH, a —OH or a —OPO(OH)2 group; R4 represents a hydrogen atom or a fluorine atom; R5 represents a hydrogen atom or a —OH group; wherein at least one of R3 or R5 is different from a hydrogen atom; when R3 represents a —COOH, —OH or —OPO(OH)2 group, then R5 represents a hydrogen atom; when R5 represents a —OH group, then R3 and R4 represent hydrogen atoms; and R6 is selected from an optionally substituted phenyl, heteroaryl, cycloalkyl and heterocycloalkyl group; and the preparation and the therapeutic uses of the compounds of formula (I) as inhibitors and degraders of estrogen receptors, useful especially in the treatment of cancer.