公开(公告)号：WO2022084479A1

公开(公告)日：2022-04-28

申请号：PCT/EP2021/079278

申请日：2021-10-21

Applicant: MISSION THERAPEUTICS LIMITED

Inventor： LUCKHURST, Christopher Andrew ,  KEMP, Mark Ian ,  THOMPSON, Paul William

IPC: A61P3/00 ,  A61P9/00 ,  A61P13/00 ,  A61P25/00 ,  A61P25/28 ,  A61P29/00 ,  A61P35/00 ,  C07D413/12 ,  A61K31/5395

Abstract: The present invention relates to a class of N-cyanopyrrolidines with activity as inhibitors of the deubiquitylating enzyme USP30, having utility in a variety of therapeutic areas, including conditions involving mitochondrial dysfunction, cancer and fibrosis: Formula (I).

公开(公告)号：WO2020212351A1

公开(公告)日：2020-10-22

申请号：PCT/EP2020/060468

申请日：2020-04-14

Applicant: MISSION THERAPEUTICS LIMITED

Inventor： KEMP, Mark Ian ,  LUCKHURST, Christopher Andrew ,  THOMPSON, Paul William

IPC: C07D401/12 ,  C07D403/12 ,  A61K31/4439 ,  A61K31/506 ,  A61P35/00

Abstract: The present invention relates to a class of substituted-cyanopyrrolidines with activity as inhibitors of the deubiquitylating enzyme USP30, having utility in a variety of therapeutic areas, including conditions involving mitochondrial dysfunction, cancer and fibrosis: (I).

公开(公告)号：WO2019171042A1

公开(公告)日：2019-09-12

申请号：PCT/GB2019/050608

申请日：2019-03-05

Applicant: MISSION THERAPEUTICS LIMITED

Inventor： THOMPSON, Paul William ,  PHELAN, Anne ,  STOCKLEY, Martin Lee ,  KEMP, Mark Ian

IPC: A61K31/4025 ,  A61K9/00 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4192 ,  A61K31/4196 ,  A61K31/422 ,  A61K31/4245 ,  A61K31/425 ,  A61P11/00 ,  A61P13/00 ,  A61P43/00

Abstract: The present invention relates to novel treatments of fibrotic diseases, including, inter alia, fibrosis of the lung, liver and kidney, and to substituted-cyanopyrrolidines of formula (I) having activity as inhibitors of ubiquitin specific peptidase 30 (USP30), and compositions containing said inhibitors, for use in said treatments (I).

公开(公告)号：WO2018060742A1

公开(公告)日：2018-04-05

申请号：PCT/GB2017/052949

申请日：2017-10-02

Applicant: MISSION THERAPEUTICS LIMITED

Inventor： STOCKLEY, Martin Lee ,  KEMP, Mark Ian ,  MADIN, Andrew

IPC: C07D487/04 ,  C07D498/04 ,  C07D403/12 ,  C07D401/12 ,  C07D417/12 ,  A61K31/407 ,  A61P25/28 ,  A61P35/00

Abstract: The present invention relates to a class of substituted-cyanopyrrolidines of Formula (I) with activity as inhibitors of deubiquitilating enzymes, in particular, ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30), having utility in a variety of therapeutic areas including cancer and conditions involving mitochondrial dysfunction. (Formula (I))

Abstract translation: 本发明涉及一类具有去泛素化酶抑制剂活性的式（I）取代的氰基吡咯烷，特别是泛素C末端水解酶30或泛素特异性肽酶30（USP30）， 可用于多种治疗领域，包括癌症和涉及线粒体功能障碍的病症。 （式（I））

公开(公告)号：WO2021239863A1

公开(公告)日：2021-12-02

申请号：PCT/EP2021/064166

申请日：2021-05-27

Applicant: MISSION THERAPEUTICS LIMITED

Inventor： LUCKHURST, Christopher Andrew ,  KEMP, Mark Ian ,  THOMPSON, Paul William

IPC: C07D413/12 ,  A61K31/422 ,  A61K31/4245 ,  A61K31/4025 ,  A61P35/00 ,  A61P25/00 ,  A61P25/28 ,  A61P3/00 ,  A61P3/10 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00

Abstract: The present invention relates to a class of N-cyanopyrrolidines with activity as inhibitors of the deubiquitylating enzyme USP30, having utility in a variety of therapeutic areas, including conditions involving mitochondrial dysfunction, cancer and fibrosis: Formula (I), Formula (II)..

公开(公告)号：WO2021204856A1

公开(公告)日：2021-10-14

申请号：PCT/EP2021/059032

申请日：2021-04-07

Applicant: MISSION THERAPEUTICS LIMITED

Inventor： LUCKHURST, Christopher Andrew ,  KEMP, Mark Ian ,  THOMPSON, Paul William

IPC: C07D413/12 ,  A61P35/00 ,  A61P43/00 ,  A61K31/421

Abstract: The present invention relates to a class of N-cyanopyrrolidines with activity as inhibitors of the deubiquitylating enzyme USP30, having utility in a variety of therapeutic areas, including conditions involving mitochondrial dysfunction, cancer and fibrosis:.

公开(公告)号：WO2017103614A1

公开(公告)日：2017-06-22

申请号：PCT/GB2016/053971

申请日：2016-12-16

Applicant: MISSION THERAPEUTICS LIMITED

Inventor： KEMP, Mark Ian ,  STOCKLEY, Martin Lee ,  MADIN, Andrew

IPC: C07D403/12 ,  C07D401/12 ,  C07D403/14 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04 ,  C07D207/09 ,  A61K31/4025 ,  A61K31/407 ,  A61P25/28 ,  A61P35/00

CPC classification number: C07D401/12 ,  C07D207/09 ,  C07D403/12 ,  C07D403/14 ,  C07D413/12 ,  C07D417/12 ,  C07D417/14 ,  C07D471/04 ,  C07D487/04

Abstract: The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C- terminal hydrolase 30 or Ubiquitin Specific Peptidase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of conditions involving mitochondrial dysfunction and cancer. Compounds of the invention include compounds having the formula (I): (I) or a pharmaceutically acceptable salt thereof, wherein R 1a , R 1b , R 1c , R 1d , R 1e , R 1f , R 1g , R 2 , X, L and A are as defined herein.

Abstract translation: 本发明涉及用于制备去泛素化酶（DUB）抑制剂的新型化合物和方法。 特别地，本发明涉及抑制泛素C-末端水解酶30或泛素特异性肽酶30（USP30）。 本发明进一步涉及DUB抑制剂在治疗涉及线粒体功能障碍和癌症的病症中的用途。 本发明的化合物包括具有式（I）的化合物：其中R 1，R 1， R 1d，R 1e，R 1f，R 1g，R 2， X，L和A如本文所定义。

公开(公告)号：WO2021249909A1

公开(公告)日：2021-12-16

申请号：PCT/EP2021/065112

申请日：2021-06-07

Applicant: MISSION THERAPEUTICS LIMITED

Inventor： LUCKHURST, Christopher Andrew ,  KEMP, Mark Ian ,  THOMPSON, Paul William ,  STOCKLEY, Martin Lee

IPC: C07D487/04 ,  A61K31/422 ,  A61K31/407 ,  A61K31/4439 ,  A61P35/00 ,  A61P25/00 ,  A61P25/28 ,  A61P3/00 ,  A61P3/10 ,  A61P9/00 ,  A61P9/10 ,  A61P11/00

Abstract: The present invention relates to hexahydropyrrolo[3,4-b]pyrrole-5(1H)-carbonitriles with activity as inhibitors of the deubiquitylating enzyme USP30, having utility in a variety of therapeutic areas, including conditions involving mitochondrial dysfunction, cancer and fibrosis:.

公开(公告)号：WO2018060691A1

公开(公告)日：2018-04-05

申请号：PCT/GB2017/052882

申请日：2017-09-27

Applicant: MISSION THERAPEUTICS LIMITED

Inventor： STOCKLEY, Martin Lee ,  KEMP, Mark Ian

IPC: C07D401/14 ,  C07D413/14 ,  C07D401/04 ,  C07D413/04 ,  C07D471/04 ,  C07D471/14 ,  A61K31/445 ,  A61K31/5377 ,  A61P35/00

Abstract: The present invention relates to a class of cyano-substituted-heterocycles of Formula (I) with activity as inhibitors of deubiquitilating enzymes, in particular, ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30), having utility in a variety of therapeutic areas including cancer and conditions involving mitochondrial dysfunction. (I)

Abstract translation: 本发明涉及一类具有去泛素化酶抑制剂活性的式（I）氰基取代的杂环化合物，特别是遍在蛋白C-末端水解酶30或泛素特异性肽酶30（USP30 ），用于各种治疗领域，包括癌症和涉及线粒体功能障碍的病症。 （I）

公开(公告)号：WO2018060689A1

公开(公告)日：2018-04-05

申请号：PCT/GB2017/052880

申请日：2017-09-27

Applicant: MISSION THERAPEUTICS LIMITED

Inventor： STOCKLEY, Martin Lee ,  KEMP, Mark Ian ,  MADIN, Andrew ,  WOODROW, Michael David ,  JONES, Alison

IPC: C07D207/09 ,  C07D401/12 ,  C07D403/06 ,  C07D413/12 ,  C07D417/12 ,  C07D471/04 ,  A61K31/4025 ,  A61P35/00

Abstract: The present invention relates to substituted-cyanopyrrolidines of Formula (I) with activity as inhibitors of deubiquitilating enzymes, in particular, ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30), having utility in a variety of therapeutic areas including cancer and conditions involving mitochondrial dysfunction. (I)

Abstract translation: 本发明涉及具有去泛素化酶抑制剂活性的式（I）取代氰基吡咯烷，特别是泛素C末端水解酶30或泛素特异性肽酶30（USP30），其具有 包括癌症和涉及线粒体功能障碍的各种治疗领域。 （I）