公开(公告)号：US10544132B2

公开(公告)日：2020-01-28

申请号：US15763698

申请日：2016-09-29

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 ,  C07D403/06 ,  C07D405/12 ,  C07D413/12 ,  C07D209/48 ,  A61P35/00

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：US11261171B1

公开(公告)日：2022-03-01

申请号：US16680969

申请日：2019-11-12

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: C07D401/06 ,  A61K31/5377 ,  A61K31/506 ,  A61K31/501 ,  A61K31/496 ,  A61K31/4545 ,  A61K31/444 ,  A61K31/4439 ,  A61P35/00 ,  C07D417/14 ,  C07D409/14 ,  C07D407/14 ,  C07D403/06 ,  C07D401/14 ,  C07D405/14 ,  C07D413/14 ,  C07D403/14 ,  C07D487/04 ,  C07B59/00 ,  C07D487/08 ,  A61K45/06

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：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：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：US10981898B2

公开(公告)日：2021-04-20

申请号：US16535931

申请日：2019-08-08

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 ,  C07D403/06 ,  C07D405/12 ,  C07D413/12 ,  C07D209/48 ,  C07D413/06 ,  C07D403/12 ,  C07F9/572 ,  A61P35/00

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：US10526311B2

公开(公告)日：2020-01-07

申请号：US15763724

申请日：2016-09-29

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: C07D401/06 ,  A61K31/4439 ,  C07D401/14 ,  C07D403/06 ,  C07D407/14 ,  C07D409/14 ,  C07D417/14 ,  A61P35/00 ,  A61K31/444 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/501 ,  A61K31/506 ,  A61K31/5377 ,  A61K45/06

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：US09458158B2

公开(公告)日：2016-10-04

申请号：US14836326

申请日：2015-08-26

Applicant: ASTEX THERAPEUTICS LIMITED

Inventor： Ildiko Maria Buck ,  Gianni Chessari ,  Steven Howard ,  David Charles Rees ,  Alison Jo-Anne Woolford

IPC: C07D471/04 ,  C07D498/04 ,  A61K31/519 ,  A61K31/4985 ,  A61K31/437 ,  A61K31/5386 ,  A61K45/06 ,  A61K31/5383 ,  C07D498/10

CPC classification number: C07D471/04 ,  A61K31/437 ,  A61K31/4985 ,  A61K31/519 ,  A61K31/5383 ,  A61K31/5386 ,  A61K45/06 ,  C07D498/04 ,  C07D498/10 ,  A61K2300/00

Abstract: The invention relates to bicyclic heterocycle compounds of formula (I): or tautomeric or stereochemically isomeric forms, N-oxides, pharmaceutically acceptable salts or the solvates thereof; wherein R1, R2, R3, A, W, U and V are as defined herein; to pharmaceutical compositions comprising said compounds and to the use of said compounds in the treatment of diseases, e.g. cancer.