公开(公告)号：US11771711B2

公开(公告)日：2023-10-03

申请号：US17966504

申请日：2022-10-14

Applicant: GlaxoSmithKline Intellectual Property Development Limited

Inventor： Andrew B. Benowitz ,  David T. Fosbenner ,  Bryan Wayne King ,  Stuart Paul Romeril

IPC: A61K31/675 ,  A61P35/02 ,  A61K31/44 ,  C07D213/85 ,  C07F9/58

CPC classification number: A61K31/675 ,  A61K31/44 ,  A61P35/02 ,  C07D213/85 ,  C07F9/58 ,  C07B2200/13

Abstract: The invention relates to substituted pyridine derivatives that are inhibitors of the activity of DNA methyltransferase 1 (DNMT1). The invention also relates to pharmaceutical compositions comprising such compounds and methods of using such compounds in the treatment of cancer, pre-cancerous syndromes, beta haemoglobinopathy disorders, and other diseases associated with inappropriate DNMT1 activity.

公开(公告)号：US10975056B2

公开(公告)日：2021-04-13

申请号：US16309121

申请日：2017-06-13

Applicant: GlaxoSmithKline Intellectual Property Development Limited ,  Cancer Research Technology Ltd.

Inventor： Nicholas David Adams ,  Andrew B. Benowitz ,  María Lourdes Rueda Benede ,  Karen Anderson Evans ,  David T Fosbenner ,  Bryan Wayne King ,  Mei Li ,  Juan Ignacio Luengo ,  William Henry Miller ,  Alexander Joseph Reif ,  Stuart Paul Romeril ,  Stanley J. Schmidt ,  Roger J. Butlin ,  Kristin M. Goldberg ,  Allan M. Jordan ,  Christopher S. Kershaw ,  Ali Raoof ,  Bohdan Waszkowycz

IPC: C07D401/12 ,  C07D401/04 ,  C07D213/73 ,  C07D213/74 ,  C07D413/14 ,  C07D417/12 ,  A61P37/00 ,  A61P35/00 ,  C07D401/14

Abstract: The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): wherein Yar, X1ar, X2ar, R1ar, R2ar, R3ar, R4ar and R5ar are as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

公开(公告)号：US20230101987A1

公开(公告)日：2023-03-30

申请号：US17966504

申请日：2022-10-14

Applicant: GlaxoSmithKline Intellectual Property Development Limited

Inventor： Andrew B. BENOWITZ ,  David T. Fosbenner ,  Bryan Wayne King ,  Stuart Paul Romeril

IPC: A61K31/675 ,  C07F9/58 ,  C07D213/85 ,  A61P35/02 ,  A61K31/44

Abstract: The invention relates to substituted pyridine derivatives that are inhibitors of the activity of DNA methyltransferase 1 (DNMT1). The invention also relates to pharmaceutical compositions comprising such compounds and methods of using such compounds in the treatment of cancer, pre-cancerous syndromes, beta haemoglobinopathy disorders, and other diseases associated with inappropriate DNMT1 activity.

公开(公告)号：US12285436B2

公开(公告)日：2025-04-29

申请号：US18358998

申请日：2023-07-26

Applicant: GlaxoSmithKline Intellectual Property Development Limited

Inventor： Andrew B. Benowitz ,  David T. Fosbenner ,  Bryan Wayne King ,  Stuart Paul Romeril ,  Megan Ketchum ,  Todd Koretke ,  Elizabeth Ann Moroz ,  Grace Price

IPC: A61K31/675 ,  A61K31/44 ,  A61P35/02 ,  C07D213/85 ,  C07F9/58

Abstract: The invention relates to substituted pyridine derivatives that are inhibitors of the activity of DNA methyltransferase 1 (DNMT1). The invention also relates to pharmaceutical compositions comprising such compounds and methods of using such compounds in the treatment of cancer, pre-cancerous syndromes, beta haemoglobinopathy disorders, and other diseases associated with inappropriate DNMT1 activity.

公开(公告)号：US11377440B2

公开(公告)日：2022-07-05

申请号：US16652221

申请日：2018-10-04

Applicant: GlaxoSmithKline Intellectual Property Development Limited

Inventor： David T. Fosbenner ,  Todd L. Graybill ,  Jianxing Kang ,  Bryan W. King ,  Yunfeng Lan ,  Lara Kathryn Leister ,  Mukesh K. Mahajan ,  John F. Mehlmann ,  Angel I. Morales-Ramos ,  George Scott Pesiridis ,  Joshi M. Ramanjulu ,  Joseph J. Romano ,  Stuart Paul Romeril ,  Mark J. Schulz ,  Huiqiang Zhou ,  Junya Qu

IPC: C07D403/14 ,  C07D401/14 ,  C07D405/14

Abstract: Disclosed are compounds having the formula: (I) wherein q, r, s, A, B, C, RA1, RA2, RB1, RB2, RC1, RC2, R3, R4, R5, R6, R14, R15, R16, R17, Rx, and Ry are as defined herein, or a tautomer thereof, or a salt, particularly a pharmaceutically acceptable salt, thereof.