公开(公告)号：US11364211B2

公开(公告)日：2022-06-21

申请号：US15564863

申请日：2016-04-08

Applicant: MEDICAL RESEARCH COUNCIL

Inventor： Anne Bertolotti ,  Indrajit Das ,  Agnieszka Krzyzosiak ,  Adrien Rousseau ,  Kim Schneider ,  Anna Gudny Sigurdardottir

IPC: A61K31/155 ,  C07C281/18 ,  C07D213/61 ,  A61P21/00 ,  A61P25/14 ,  C12Q1/42 ,  C07D239/30 ,  A61P25/28 ,  G01N33/573 ,  C12N11/14 ,  G01N21/31 ,  G01N33/53

Abstract: The present invention discloses a method to discover selective inhibitors of phosphatases. Thus the invention provides a method for screening a test compound to determine whether the compound binds a holophosphatase selectively or non-selectively comprising: i) providing a first holophosphatase wherein said holophosphatase is captured/immobilised; ii) testing a test compound for its ability to bind to the first holophosphatase; iii) providing a second holophosphatase wherein said second holophosphatase is captured/immobilised; iv) testing the same test compound for its ability to bind to the second holophosphatase; v) comparing the binding of the test compound to said first holophosphatase with the binding to said second phosphatase wherein a compound that binds a holophosphatase selectively will bind to said first holophosphatase but not said second holophosphatase; or will bind to said second holophosphatase but not said first; or wherein a compound that binds a holophosphatase non-selectively will bind to both said first holophosphatase and said second holophosphatase.

公开(公告)号：US11337941B2

公开(公告)日：2022-05-24

申请号：US16804353

申请日：2020-02-28

Applicant: Medical Research Council

Inventor： Anne Bertolotti ,  Indrajit Das ,  Agnieszka Krzyzosiak ,  Adrien Rousseau ,  Kim Schneider ,  Anna Gudny Sigurdardottir

IPC: A61K31/155 ,  C07C281/18 ,  A61P25/28 ,  A61P25/14 ,  A61P21/00 ,  C12Q1/42 ,  C07D239/30 ,  C07D213/61 ,  G01N33/573 ,  C12N11/14 ,  G01N21/31 ,  G01N33/53

Abstract: The present invention relates to inhibitors of PPP1 R15A and PPP1 R15B and their use in therapy, particularly in the treatment of a disease state alleviated by the inhibition of PPP1 R15A and PPP1 R15B, for example a disorder associated with accumulation of misfolded proteins or proteostatsis disorder. Compounds of the invention include compounds having the formula IA or a pharmaceutically acceptable salt thereof, wherein R1a, R3a, R5a, Xa and Ya are as defined herein.

公开(公告)号：US11331286B2

公开(公告)日：2022-05-17

申请号：US16804402

申请日：2020-02-28

Applicant: Medical Research Council

Inventor： Anne Bertolotti ,  Indrajit Das ,  Agnieszka Krzyzosiak ,  Adrien Rousseau ,  Kim Schneider ,  Anna Gudny Sigurdardottir

IPC: A61K31/155 ,  C07C281/18 ,  A61P25/28 ,  A61P25/14 ,  A61P21/00 ,  C12Q1/42 ,  C07D239/30 ,  C07D213/61 ,  G01N33/573 ,  C12N11/14 ,  G01N21/31 ,  G01N33/53

Abstract: The present invention relates to inhibitors of PPP1 R15A and PPP1 R15B and their use in therapy, particularly in the treatment of a disease state alleviated by the inhibition of PPP1 R15A and PPP1 R15B, for example a disorder associated with accumulation of misfolded proteins or proteostatsis disorder. Compounds of the invention include compounds having the formula IA or a pharmaceutically acceptable salt thereof, wherein R1a, R3a, R5a, Xa and Ya are as defined herein.

公开(公告)号：US11154519B2

公开(公告)日：2021-10-26

申请号：US15564834

申请日：2016-04-08

Applicant: MEDICAL RESEARCH COUNCIL

Inventor： Anne Bertolotti ,  Indrajit Das ,  Agnieszka Krzyzosiak ,  Adrien Rousseau ,  Kim Schneider ,  Anna Gudny Sigurdardottir

IPC: C07C281/18 ,  A61K31/155 ,  C12Q1/42 ,  C07D239/30 ,  C07D213/61 ,  A61P25/28 ,  G01N33/573 ,  A61P25/14 ,  A61P21/00 ,  C12N11/14 ,  G01N21/31 ,  G01N33/53

Abstract: The present invention relates to inhibitors of PPP1 R15A and PPP1 R15B and their use in therapy, particularly in the treatment of a disease state alleviated by the inhibition of PPP1 R15A and PPP1 R15B, for example a disorder associated with accumulation of misfolded proteins or proteostatsis disorder. Compounds of the invention include compounds having the formula IA or a pharmaceutically acceptable salt thereof, wherein R1a, R3a, R5a, Xa and Ya are as defined herein.