Substituted pyridines as inhibitors of DNMT1
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.
Cancer Research Technology Ltd. GlaxoSmithKline Intellectual Property Development Limited
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Stanley J. Nicholas David Stuart Paul Bohdan Alexander Joseph Christopher S. María Lourdes Mei Bryan Wayne Juan Ignacio William Henry Karen Anderson David T Andrew B. Roger J. Ali Kristin M. Allan M.
Schmidt Adams Romeril Waszkowycz Reif Kershaw Rueda Benede Li King Luengo Miller Evans Fosbenner Benowitz Butlin Raoof Goldberg Jordan