Patent number: 10975056
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.
Type:
Grant
Filed:
June 13, 2017
Date of Patent:
April 13, 2021
Assignees:
GlaxoSmithKline Intellectual Property Development Limited, Cancer Research Technology Ltd.
Inventors:
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
Publication number: 20190194166
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.
Type:
Application
Filed:
June 13, 2017
Publication date:
June 27, 2019
Inventors:
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, Kristen M. GOLDBERG, Allan M. JORDAN, Christopher S. KERSHAW, Ali RAOOF, Bohdan WASZKOWYCS