- CYCLIC DINUCLEOTIDES AS STING AGONISTS
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Disclosed are compounds, compositions and methods for treating of diseases, syndromes, or disorders that are affected by the modulation of STING. Such compounds are represented by Formula (I) as follows: wherein B2,X2, R2a, R2b, R2c, Z-M-Y, Y1-M1Z1, B1, X1, R1a, R1b, R1c are as defined herein.
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Page/Page column 112; 115-116
(2019/07/19)
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- CROSSLINKED NUCLEIC ACID GUNA, METHOD FOR PRODUCING SAME, AND INTERMEDIATE COMPOUND
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The present invention provides a method for producing guanidine crosslinked artificial nucleic acid (abbreviated hereinafter as GuNA), and an intermediate compound for the production thereof. Specifically, the present invention provides a method for producing a compound represented by general formula I: (in the formula, R1, R2, R3, R4, R5, R6, m and ring A are as defined in the specification) or a salt thereof wherein a reducing agent is reacted with a compound represented by general formula II: (in the formula, R1, R2, R3, R4, R5, R6, m, and ring A′ are as defined in the specification).
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- Oligonucleotides containing novel 4'-C- or 3'-C-(aminoalkyl)-branched thymidines
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The synthesis of four novel 3'-C-branched and 4'-C-branched nucleosides and their transformation into the corresponding 3'-O-phosphoramidite building blocks for automated oligonucleotide synthesis is reported. The 4'-C-branched key intermediate 11 was synthesized by a convergent strategy and converted to its 2-O-methyl and 2'-deoxy-2'-fluoro derivatives, leading to the preparation of novel oligonucleotide analogues containing 4'-C-(aminomethyl)-2'-O-methyl monomer X and 4'-C-(aminomethyl)-2'-deoxy-2'-fluoro monomer Y (Schemes 2 and 3). In general, increased binding affinity towards complementary single- stranded DNA and RNA was obtained with these analogues compared to the unmodified references (Table 1). The presence of monomer X or monomer Y in a 2'-O-methyl-RNA oligonucleotide had a negative effect on the binding affinity of the 2'-O-methyl-RNA oligonucleotide towards DNA and RNA. Starting from the 3'-C-allyl derivative 28, 3'-C-(3-aminopropyl)-protected nucleosides and 3'- O-phosphoramidite derivatives were synthesized, leading to novel oligonucleotide analogues containing 3'-C-(3-aminopropyl)thymidine monomer Z or the corresponding 3'-C-(3-aminopropyl)-2'-O,5-dimethyluridine monomer W (Schemes 4 and 5). Incorporation of the 2'-deoxy monomer Z induced no significant changes in the binding affinity towards DNA but decreased binding affinity towards RNA, while the 2'-O-methyl monomer Z induced decreased binding affinity towards DNA as well as RNA complements (Table 2).
- Pfundheller, Henrik M.,Bryld, Torsten,Olsen, Carl E.,Wengel, Jesper
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p. 128 - 151
(2007/10/03)
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