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As expected, modifications in the C-6 position of pyrimidines are highlydestabilizing. Oligonucleotides containing 6-azapyrimidines (16) have beenshown not only to reduce the thermal melting temperature (Tm) value by 1-2 °Cper modification, but also to enhance the nuclease stability of oligonucleotidesand to support E. coli RNase H-induced deradation of RNA targets. 254ONHN + HHHONoONOo(16)PYRIMIDINE MODIFICATIONS (Non-nucleotide)The increasing interest in the early 1970s in properties and use ofinterferon (IFN) together with the difficulty in producing useful amounts ofinterferon (IFN) led to the search for agents that would induce IFN in the host.Precedenced at that time for interferon (IFN) inducers included viruses andbacterial wall constituents and entities of large molecular weight such as thepolynucleotides. There were also several examples of low molecular weightsubstances such as certain antibiotics and the antiviral agent, tilorone. 255 In1976 it was reported that 6-methyl pyrimidinone (2-amino-5-bromo-6-methyl-4-(3H) pyrimidinone, ABMP) induced circulating levels of interferon (IFN) inseveral animal specis upon oral or intraperitoneal administration. 256 Subsequentstructure-activity studies yielded a more potent and less toxic 6-phenyl ananlog50Pyrimidine…..