公开(公告)号：US20150353537A1

公开(公告)日：2015-12-10

申请号：US14436319

申请日：2013-10-18

Applicant: ASTEX THERAPEUTICS LIMITED

Inventor： Gianni CHESSARI ,  Christopher Norbert JOHNSON ,  Lee William PAGE ,  Ildiko Maria BUCK ,  James Edward Harvey DAY ,  Steven HOWARD ,  Gordon SAXTY ,  Christopher William MURRAY

IPC: C07D471/04 ,  C07D519/00

CPC classification number: C07D403/14 ,  C07D471/04 ,  C07D519/00

Abstract: The invention relates to new bicyclic heterocycle compounds, to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.

公开(公告)号：US20140288053A1

公开(公告)日：2014-09-25

申请号：US14354832

申请日：2012-10-26

Applicant: ASTEX THERAPEUTICS LIMITED

Inventor： Valerio Berdini ,  Gordon Saxty ,  Patrick Rene Angibaud ,  Olivier Alexis Georges Querolle ,  Virginie Sophie Poncelet ,  Bruno Roux ,  Lieven Meerpoel

IPC: C07D471/04 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/4985

CPC classification number: A61K31/4985 ,  A61K31/506 ,  A61K31/5377 ,  C07D471/04

Abstract: The invention relates to new pyridopyrazine 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.

Abstract translation: 本发明涉及新的吡啶并吡嗪衍生物化合物，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以及所述化合物在治疗疾病中的用途。 癌症。

公开(公告)号：US20140288040A1

公开(公告)日：2014-09-25

申请号：US14355780

申请日：2012-10-31

Applicant: ASTEX THERAPEUTICS LIMITED

Inventor： Andrew James Woodhead ,  Gianni Chessari ,  Gilbert Ebai Besong ,  Maria Grazia Carr ,  Steven Douglas Hiscock ,  Michael Alistair O'Brien ,  David Charles Rees ,  Susanne Maria Saalau-Bethell ,  Hendrika Maria Gerarda Willems ,  Neil Thomas Thompson

IPC: A61K31/505 ,  A61K31/137 ,  A61K45/06 ,  C07C217/74 ,  A61K31/135 ,  C07D239/42 ,  C07C237/20 ,  A61K31/165 ,  C07D211/70 ,  A61K31/4409 ,  C07D295/027 ,  A61K31/4465 ,  A61K31/4462 ,  A61K31/397 ,  C07C217/58

CPC classification number: A61K31/505 ,  A61K31/135 ,  A61K31/137 ,  A61K31/165 ,  A61K31/397 ,  A61K31/4409 ,  A61K31/4462 ,  A61K31/4465 ,  A61K45/06 ,  C07B2200/05 ,  C07C217/58 ,  C07C217/60 ,  C07C217/62 ,  C07C217/74 ,  C07C217/90 ,  C07C225/12 ,  C07C233/18 ,  C07C233/25 ,  C07C235/46 ,  C07C237/04 ,  C07C237/06 ,  C07C237/08 ,  C07C237/10 ,  C07C237/12 ,  C07C237/20 ,  C07C243/34 ,  C07C251/48 ,  C07C255/24 ,  C07C255/29 ,  C07C255/37 ,  C07C255/46 ,  C07C255/54 ,  C07C259/06 ,  C07C271/12 ,  C07C275/36 ,  C07C311/04 ,  C07C311/08 ,  C07C311/29 ,  C07C313/06 ,  C07C317/22 ,  C07C323/25 ,  C07C2601/02 ,  C07C2601/04 ,  C07C2601/08 ,  C07C2601/14 ,  C07C2601/16 ,  C07D205/04 ,  C07D207/14 ,  C07D207/335 ,  C07D209/08 ,  C07D209/14 ,  C07D209/44 ,  C07D211/26 ,  C07D211/56 ,  C07D211/70 ,  C07D213/38 ,  C07D213/64 ,  C07D213/65 ,  C07D213/68 ,  C07D213/73 ,  C07D213/74 ,  C07D213/75 ,  C07D213/81 ,  C07D213/84 ,  C07D217/02 ,  C07D231/12 ,  C07D233/24 ,  C07D233/64 ,  C07D237/14 ,  C07D239/34 ,  C07D239/42 ,  C07D241/18 ,  C07D241/20 ,  C07D241/24 ,  C07D243/14 ,  C07D263/32 ,  C07D265/36 ,  C07D271/10 ,  C07D277/68 ,  C07D285/13 ,  C07D295/02 ,  C07D295/027 ,  C07D295/185 ,  C07D295/192 ,  C07D305/06 ,  C07D305/08 ,  C07D307/14 ,  C07D307/22 ,  C07D307/79 ,  C07D309/06 ,  C07D309/12 ,  C07D309/14 ,  C07D319/18 ,  C07D513/04

Abstract: The invention provides compounds of the formula (6): or a salt, N-oxide or tautomer thereof, wherein A is CH, CF or nitrogen; E is CH, CF or nitrogen; and R0 is hydrogen or C1-2 alkyl; R1a is selected from CONH2; CO2H; an optionally substituted acyclic C1-8 hydrocarbon group; and an optionally substituted monocyclic carbocyclic or heterocyclic group of 3 to 7 ring members, of which 0, 1, 2, 3 or 4 are heteroatom ring members selected from O, N and S; R2 is selected from hydrogen and a group R2a; R2a is selected from an optionally substituted acyclic C1-8 hydrocarbon group; an optionally substituted monocyclic carbocyclic or heterocyclic group of 3 to 7 ring members, of which 0, 1 or 2 ring members are heteroatom ring members selected from O, N and S; and an optionally substituted bicyclic heterocyclic group of 9 or 10 ring members, of which 1 or 2 ring members are nitrogen atoms; wherein at least one of R1 and R2 is other than hydrogen; R3 is an optionally substituted 3- to 10-membered monocyclic or bicyclic carbocyclic or heterocyclic ring containing 0, 1, 2 or 3 heteroatom ring members selected from N, O and S; R4a is selected from halogen; cyano; C1-4 alkyl optionally substituted with one or more fluorine atoms; C1-4 alkoxy optionally substituted with one or more fluorine atoms; hydroxy-C1-4 alkyl; and C1-2 alkoxy-C1-4 alkyl; R5 is selected from hydrogen and a substituent R5a; and R5a is selected from C1-2 alkyl optionally substituted with one or more fluorine atoms; C1-3 alkoxy optionally substituted with one or more fluorine atoms; halogen; cyclopropyl; cyano; and amino. The compounds have activity against hepatitis C virus and can be used in the prevention or treatment of hepatitis C viral infections.

Abstract translation: 本发明提供式（6）化合物或其盐，N-氧化物或互变异构体，其中A为CH，CF或氮; E是CH，CF或氮; 和R 0是氢或C 1-2烷基; R1a选自CONH2; CO2H; 任选取代的非环C 1-8烃基; 和3至7个环成员的任选取代的单环碳环或杂环基，其中0,1,2,3或4为选自O，N和S的杂原子环成员; R2选自氢和基团R 2a; R2a选自任选取代的无环C 1-8烃基; 3至7个环成员的任选取代的单环碳环或杂环基，其中0,1或2个环成员是选自O，N和S的杂原子环成员; 和9或10个环成员的任选取代的双环杂环基，其中1或2个环成员是氮原子; 其中R 1和R 2中的至少一个不是氢; R3是含有0,1,2或3个选自N，O和S的杂原子环成员的任选取代的3至10元单环或双环碳环或杂环; R4a选自卤素; 氰基; 任选被一个或多个氟原子取代的C 1-4烷基; 任选被一个或多个氟原子取代的C 1-4烷氧基; 羟基-C 1-4烷基; 和C 1-2烷氧基-C 1-4烷基; R5选自氢和取代基R5a; 并且R 5a选自任选被一个或多个氟原子取代的C 1-2烷基; 任选被一个或多个氟原子取代的C 1-3烷氧基; 卤素; 环丙基 氰基; 和氨基。 该化合物具有抗丙型肝炎病毒的活性，可用于预防或治疗丙型肝炎病毒感染。

公开(公告)号：US20250074900A1

公开(公告)日：2025-03-06

申请号：US18785847

申请日：2024-07-26

Applicant: ASTEX THERAPEUTICS LIMITED ,  CANCER RESEARCH TECHNOLOGY LIMITED

Inventor： Steven HOWARD ,  Benjamin David CONS ,  Jeffrey David ST. DENIS ,  Charlotte Mary GRIFFITHS-JONES ,  Steven Douglas HISCOCK ,  Rhian Sara HOLVEY ,  Alan Richard BURNS ,  David COUSIN ,  Hannah Louise DEXTER ,  Guillaume François PARRA ,  John Paul WATTS ,  Robert JEWELL ,  Jennifer Ann STOCKWELL ,  Kim Louise HIRST ,  Isabelle Anne LEMASSON ,  David John NASH ,  James Daniel OSBORNE ,  Jonas Calleja PRIEDE ,  Nicholas Paul RICHARDS ,  Aaron Michael DUMAS ,  Brian Christopher BISHOP ,  David PARRY-JONES ,  Jeremy Peter SCOTT ,  Meenakshi Sundaram SHANMUGHAM ,  Peter Richard MULLENS ,  David Charles LATHBURY ,  Darren James DIXON ,  Matthew James GAUNT

IPC: C07D405/06

Abstract: The invention relates to processes for preparing isoindolin-1-one derivatives, and in particular processes for preparing (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid. The invention also relates to crystalline forms of the compound (2S,3S)-3-(4-chlorophenyl)-3-[(1R)-1-(4-chlorophenyl)-7-fluoro-5-[(1S)-1-hydroxy-1-(oxan-4-yl)propyl]-1-methoxy-3-oxo-2,3-dihydro-1H-isoindol-2-yl]-2-methylpropanoic acid and its salts.

公开(公告)号：US12202828B2

公开(公告)日：2025-01-21

申请号：US18069571

申请日：2022-12-21

Applicant: ASTEX THERAPEUTICS LIMITED

Inventor： Gianni Chessari ,  Christopher Norbert Johnson ,  Steven Howard ,  James Edward Harvey Day ,  Ildiko Maria Buck ,  Charlotte Mary Griffiths-Jones ,  Gordon Saxty ,  Emiliano Tamanini ,  Nicola Elizabeth Wilsher

IPC: C07D471/04 ,  A61K31/5377

Abstract: The invention relates to new bicyclic heterocycle compounds, to pharmaceutical compositions comprising the compounds and to the use of the compounds in the treatment of diseases, e.g. cancer.

公开(公告)号：US12071429B2

公开(公告)日：2024-08-27

申请号：US17164045

申请日：2021-02-01

Applicant: ASTEX THERAPEUTICS LIMITED ,  CANCER RESEARCH TECHNOLOGY LIMITED

Inventor： Gianni Chessari ,  Steven Howard ,  Ildiko Maria Buck ,  Benjamin David Cons ,  Christopher Norbert Johnson ,  Rhian Sara Holvey ,  David Charles Rees ,  Jeffrey David St. Denis ,  Emiliano Tamanini ,  Bernard Thomas Golding ,  Ian Robert Hardcastle ,  Celine Florence Cano ,  Duncan Charles Miller ,  Martin Edward Mäntylä Noble ,  Roger John Griffin ,  James Daniel Osborne ,  Joanne Peach ,  Arwel Lewis ,  Kim Louise Hirst ,  Benjamin Paul Whittaker ,  David Wyn Watson ,  Dale Robert Mitchell

IPC: C07D405/14 ,  A61K31/4035 ,  A61P35/00 ,  C07D209/48 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D413/06 ,  C07D413/12 ,  C07F9/572

CPC classification number: C07D405/14 ,  A61K31/4035 ,  A61P35/00 ,  C07D209/48 ,  C07D403/06 ,  C07D403/12 ,  C07D405/12 ,  C07D413/06 ,  C07D413/12 ,  C07F9/5728 ,  C07B2200/05

Abstract: The invention provides a compound of formula (I):




or tautomer or a solvate or a pharmaceutically acceptable salt thereof, wherein the various substituents are as defined in the claims.

Also provided are pharmaceutical compositions containing the compounds of formula (I), processes for making the compounds and the medical uses of the compounds.

公开(公告)号：US11918576B2

公开(公告)日：2024-03-05

申请号：US16931728

申请日：2020-07-17

Applicant: ASTEX THERAPEUTICS LTD

Inventor： Eleonora Jovcheva ,  Timothy Pietro Suren Perera

IPC: A61K31/4985 ,  A61K31/498 ,  A61K31/5025 ,  A61K45/06

CPC classification number: A61K31/4985 ,  A61K31/498 ,  A61K31/5025 ,  A61K45/06 ,  A61K31/498 ,  A61K2300/00 ,  A61K31/4985 ,  A61K2300/00 ,  A61K31/5025 ,  A61K2300/00

Abstract: The invention relates to a combination of a first compound selected from N-(3,5-dimethoxyphenyl)-N′-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine or a pharmaceutically acceptable salt thereof or a solvate thereof, and N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine or a pharmaceutically acceptable salt thereof or a solvate thereof; and a second compound which is a cMet inhibitor.
The combination is for use in the treatment of a proliferative disorder, in particular for use in the treatment of cancer.
The FGFR inhibitor (N-(3,5-dimethoxyphenyl)-N-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine or a pharmaceutically acceptable salt thereof or a solvate thereof, and N-(2-fluoro-3,5-dimethoxyphenyl)-N-(1H-imidazol-2-ylmethyl)-3-(1-methyl-1H-pyrazol-4-yl)pyrido[2,3-b]pyrazin-6-amine or a pharmaceutically acceptable salt thereof or a solvate thereof) and the cMet inhibitor can be administered simultaneously, separately or sequentially.
The invention further relates to a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a combination according to the invention.

公开(公告)号：US20230227450A1

公开(公告)日：2023-07-20

申请号：US18069571

申请日：2022-12-21

Applicant: ASTEX THERAPEUTICS LIMITED

Inventor： Gianni CHESSARI ,  Christopher Norbert JOHNSON ,  Steven HOWARD ,  James Edward Harvey DAY ,  Ildiko Maria BUCK ,  Charlotte Mary GRIFFITHS-JONES ,  Gordon SAXTY ,  Emiliano TAMANINI ,  Nicola Elizabeth WILSHER

IPC: C07D471/04 ,  A61K31/5377

CPC classification number: C07D471/04 ,  A61K31/5377

Abstract: The invention relates to new bicyclic heterocycle compounds, to pharmaceutical compositions comprising the compounds and to the use of the compounds in the treatment of diseases, e.g. cancer.

公开(公告)号：US11684620B2

公开(公告)日：2023-06-27

申请号：US17125261

申请日：2020-12-17

Applicant: ASTEX THERAPEUTICS LTD

Inventor： Diego Fernando Domenico Broggini

IPC: A61K31/498 ,  A61K47/26 ,  A61K47/18 ,  A61K9/20 ,  A61K9/48 ,  C09K15/20

CPC classification number: A61K31/498 ,  A61K9/2018 ,  A61K9/2054 ,  A61K9/4858 ,  A61K47/18 ,  A61K47/26 ,  C09K15/20

Abstract: The invention relates to pharmaceutical compositions comprising N-(3,5-dimethoxyphenyl)-N′-(1-methylethyl)-N-[3-(1-methyl-1H-pyrazol-4-yl)quinoxalin-6-yl]ethane-1,2-diamine, or a pharmaceutically acceptable salt thereof or a solvate thereof; to processes for the preparation of said compositions and to the use of said compositions for the manufacture of a medicament for the prophylaxis of or the treatment, in particular the treatment, of diseases, e.g. cancer.

公开(公告)号：US20230181536A1

公开(公告)日：2023-06-15

申请号：US17920870

申请日：2021-04-23

Applicant: TAIHO PHARMACEUTICAL CO., LTD. ,  Astex Therapeutics Ltd.

Inventor： Tetsuya ABE ,  Yoko NAKATSURU ,  Hiroshi SOOTOME

IPC: A61K31/4178 ,  A61K31/427 ,  A61K31/416 ,  A61K31/422 ,  A61K31/454 ,  A61K31/496 ,  A61K31/4439 ,  A61P35/00 ,  A61P11/00 ,  A61K31/506 ,  A61K31/166 ,  A61K31/5365 ,  A61P1/18 ,  A61P1/00 ,  A61P13/10 ,  A61N5/10

CPC classification number: A61K31/4178 ,  A61K31/427 ,  A61K31/416 ,  A61K31/422 ,  A61K31/454 ,  A61K31/496 ,  A61K31/4439 ,  A61P35/00 ,  A61P11/00 ,  A61K31/506 ,  A61K31/166 ,  A61K31/5365 ,  A61P1/18 ,  A61P1/00 ,  A61P13/10 ,  A61N5/10

Abstract: A method of treating cancer comprises administering: (a) a therapeutically effective amount of a compound of Formula (I) or a pharmaceutically acceptable salt thereof; and (b) a therapeutically effective amount of an additional anti-cancer agent, to a subject in need of such treatment, the compound of Formula (I) being:




where X, R1, R2, ring A, L1, L2, L3, and R5 are as defined in this disclosure.