JEMIELITY, JACEK,FAC-DABROWSKA, KAJA,WOJTCZAK, BLAZEJ,BARANOWSKI, MAREK,NOWICKA, ANNA,KOWALSKA, JOANNA,SIKORSKI, PAWEL,WARMINSKI, MARCIN
申请号：
CA3011663
公开号：
CA3011663A1
申请日:
2017.01.27
申请国别(地区):
CA
年份:
2017
代理人:
摘要：
The present invention relates to nucleotides, analogs of mRNA 5'-end (cap) containing sulfur atom at the position 5' of 7-methylguanosine nucleoside. The disclosed compounds are recognized (bound and non-hydrolyzed) by DcpS enzyme (Decapping Scavenger), and thus may find therapeutic use as inhibitors thereof. DcpS is cap-specific enzyme with pyrophosphatase activity, which was identified as a therapeutic target in the treatment of spinal muscular atrophy (SMA). Some of the compounds disclosed have additional modifications in the phosphate chain, wh ich modulate their affinity for DcpS enzyme. The present invention also relates to mRNAs modified at the 5' end with mRNA 5'-end (cap) analogs containing 5'- phosphorothiolate moiety, which mRNAs have an increased stability and translational activity in cellular conditions, to a method of their preparation, their uses, and to a pharmaceutical formulation containing them, wherein L1 and L2 are independently selected from the group comprising O and S, wherein at least one of L1 and L2 is not O.
